Week 6 - Microbiology and Infection

Question 1

Which antibiotics should generally be used in severe/life-threatening infections?

Answer 1

Usually IV combination Rx (Beta lactam + gentamicin) initially

Use of protected Abx if risk of MDR

Prompt (<1 hour) administration

Question 2

Describe the treatment of bacterial endocarditis

Answer 2

• Seek expert opinion on treatment of endocarditis, variety of national treatment guidelines that you can consult
• Should use bactericidal rather than static drugs, extended therapy of weeks rather than days is required
• Commonly used regimen for treatment of streptococcal endocarditis (most common cause) of a native heart valve is 4 weeks of benzylpenicillin combined with gentamicin for the first 2 weeks
  
  • Although streptococci are intrinsically resistant to gentamicin, benzylpenicillin disrupts the cell wall and allows gentamicin to penetrate inside the cell = synergy

Question 3

Why are CREs important to control?

Answer 3

1. Plasmids can transfer resistance to other stories and species
2. They can be efficiently transmitted in healthcare facilities

Question 4

Which type of organism is not covered by any new antibiotics?

Answer 4

Opportunisitc gram -ves

Question 5

How is malaria diagnosed?

Answer 5

• Antigen testing
  
  • Done in UK - not used to interpreting malaria films
• Blood films (thick and thin)
  
  • Thick - confirms presence of parasite, diagnoses malaria
    
    • Blood onto slide, soluble dye added (lyses red cells), can see parasites
  • Thin - diagnoses the type of malaria
    
    • E.g. falciparum - cygnet ring/headphone inclusions
• PCR
  
  • Usually done after diagnosis

Question 6

What effect do antibiotics have on the colonic flora?

Answer 6

• Antibiotics dramaticaly alter the colonic flora
• Most of gut flora wiped out by antibiotics
• Minority species w/ resistance to antibiotics colonises gut
• Even after 2 years lack of gut flora diversity - susceptibility to C diff

Question 7

What is the first choice of antibiotic in a complicated UTI?

Answer 7

Ciprofloxacin - higher risk of deterioration in complicated if treatment isn’t effective, resistance less common with ciprofloxacin

Question 8

How should blood cultures be taken when dealing with a patient with possible bacterial endocarditis?

Answer 8

• 3 sets of blood cultures
• Taken from peripheral veins
• 10 mls of blood in each bottle
• 1 hour between first and last samples
• Meticulous sterile technique
• Taken prior to antibiotics
• Bacteraemia always present - no need to wait for fever, all/majority of cultures should be positive

Question 9

Describe the pathogenesis of bacterial pneumonia

Answer 9

Normally -

• Lungs constantly exposed to pathogens, well-evolved protection mechanisms - innate and acquired immunity
• Below level of carina should be sterile (leads to gas exchange)

Pathogenesis of Pneumonia (consolidation of lung):

• Defect in host defence - immunosuppressed individuals, smokers (destroy macrophages)
• Large inoculum e.g. inhaled particles in air when infected individual coughs
• Increased virulence of pathogen - evades immune system

Question 10

What is the aim of empirical antibiotic guidelines?

Answer 10

Promote efficacy and prudency

Protect rather than restrict antibiotics

Question 11

Give an example of how antibiotic use can lead to antimicrobial resistance

Answer 11

• Co-amoxiclav
• Amoxicillin has some activity against gram positive organisms and anaerobes
• Addition of clavulanic acid strengthens activity against anaerobes and gram-negatives by mopping up the beta-lactamase produced by these organisms resulting in higher amoxicillin concentration at the site of infection
• If target (infection causing agent is streptococci) and co-amoxiclav is used, the collateral damage will be that anaerobes, coliforms etc. are wiped out
• Sensitive organisms are wiped out, leaves resistant organisms to overgrow

Question 12

Which groups are most commonly affected by haemophilus influenzae?

Answer 12

• Older people
• Underlying lung disease
  
  • Disturbed lung architecture - COPD, pulmonary fibrosis, cystic fibrosis

Question 13

List the important predisposing risk factors for septic arthritis

Answer 13

Elderly

Pre-existing joint disease

Recent joint surgery or injection

Skin or soft tissue infection

Intravenous drug use

Indwelling catheters

Immunosuppression (including diabetes)

Question 14

Describe methods of bite avoidance

Answer 14

Physical Avoidance

• Indoors
• AC, screens on doors and windows
• Impregnated (tucked underneath mattress before sun goes down) netting
  
  • Permethrin
  • Mosquito free
• Clothing
  
  • Cover up (arms, legs, ankles, feet)
  • Spray/soak clothing

Repellant:

• Deet
  
  • 30% reapply every 4-6 hours
  • 50% reapply every 6-8 hours
  • Reapply more often if sweating, in water
  • Makes you taste bad to mosquitoes - land but don’t bite

Question 15

Describe the use of aseptic technique in infection control

Answer 15

Reduce activity in area

Keep exposure of a susceptible site to a minimum

Check sterile packs for evidence of damage or moisture

Ensure all fluid materials in date

Do not re-use single use items

Hand decontamination prior to procedures

Protect uniform/clothing with a disposable apron

Use sterile gloves

Appropriate waste disposal

Question 16

Which antibiotics are considered safe in pregnancy?

Answer 16

• Most beta lactams
  
  • Broad spectrum agents may be associated with NEC (necrotising enterocolitis) in premature infants
• Macrolides - respiratory tract infection
• Anti-tuberculants

Question 17

What is the clinical significance of pseudomonas bacteria?

Answer 17

• Causes infections in immunocompromised
• Resistant to many antibiotics

Question 18

Where are haemophilus bacteria usually found?

Answer 18

Inhabit upper respiratory tract, mouth, vagina and intestinal tract

Question 19

Give examples of other coliforms

Answer 19

Klebsiella, Enterobacter

Question 20

Describe the action of chloramphenicol

Answer 20

• Inhibits the 50S ribosome
• Excellent broad spectrum activity

Question 21

Which bacteria are sensitive/resistant to doxycycline?

Answer 21

Highly sensitive - streptococcus, staphylococcus

Sensitive - haemophilus, neisseria

Minimally sensitive - enterococcus

Resistant - E. coli and other coliforms, pseudomonas, bacteroides, clostridium

Atypicals also sensitive - Rickettsia, mycoplasma, coxiella, chlamydia, chlamydophia

Question 22

Is it appropriate practice to use two prescription charts when too busy to rewrite the first chart?

Answer 22

Always bad practice to expect nurses to work from two prescription charts

Avoidable clinical risk - things can be missed from the second prescription chart if it is not realised there are two

Question 23

Which bacteria are sensitive/resistant to ceftriaxone?

Answer 23

Highly sensitive - streptococcus, staphylococcus, E. coli, neisseria, haemophilus

Sensitive - other coliforms, bacteroides, clostridium

Resistant - enterococcus, pseudomonas

Question 24

Which antibiotic would usually be used in cellulitis?

Answer 24

Flucloxacillin - provides good cover for common causes

Question 25

Describe the mechanism of action of antibiotic which inhibit folate synthesis

Answer 25

Inhibition of folate metabolism pathway leads to impaired nucleotide synthesis and therefore impaired DNA replication

Question 26

Describe the toxicity of chloramphenicol

Answer 26

* Very toxic * Bone marrow suppression (1 in 10,000 need BMT) * Aplastic anaemia * Optic neuritis

Question 27

What are the important non-infectious causes of diarrhoea to consider when a patient presents with acute diarrhoea?

Answer 27

* Acute diarrhoea can often reflect the acute presentation of a non-infectious bowel disease * Inflammatory bowel disease (Crohn's disease/ulcerative colitis), bowel cancer, diverticular disease, chronic pancreatitis, HIV infection and ischaemic bowel * Non-gastrointestinal infection can also present with diarrhoea, can be a manifestation of sepsis syndrome (e.g. pneumococcal bacteraemia)

Question 28

What are the common bacterial pathogens/microorganisms associated with infective endocarditis?

Answer 28

Staphylococcus aureus Streptococci viridans Streptococcus gallolyticus (S. bovis) HACEK - haemophilus, aggregatibacter, cardiobacterium, eikenella, kingella Enterococci

Question 29

What indicates an uncomplicated UTI?

Answer 29

Lower urinary tract symptoms Absence of sepsis or evidence of upper tract involvement (pyelonephritis)

Question 30

How is streptococcus pneumoniae treated?

Answer 30

* Penicillin * Resistance rare in UK (\<1% in Scotland) * Beware S. Europe, Asia, N. America - travel history important * Allergy (ask what it does to them) * Macrolides (clarithromycin) * Tetracyclines (doxycycline)

Question 31

List the bacterial mechanisms for antibiotic resistance

Answer 31

1. Efflux pumps 2. Decreased uptake 3. Target alterations 4. Alternative enzyme 5. Inactivating enzymes

Question 32

Which bacteria usually cause UTIs?

Answer 32

E. coli, other coliforms Pseudomonas, enterococcus Staphylococcus

Question 33

Describe the appearance of pseudomonas bacteria

Answer 33

Rod shaped

Question 34

What are the commonest causes of jaundice (hyperbilirubinaemia)?

Answer 34

* Gallstones * Alcoholic hepatitis * Cholestasis with fever and leukocytosis commonly seen * Should always be considered in the jaundiced patient with a history of alcohol excess, especially is ratio of serum AST:ALT is greater than 2 with the values being below 500 international unit/L * Viral hepatitis * Predominantly cholestatic syndrome with marked pruritus * A, B, C, D, E, herpes simplex virus, Epstein-Barr virus, CMV * Pancreatitis * Non-alcoholic steatohepatitis * Associated with diabetes mellitus, morbid obesity * Primary biliary cholangitis * Drugs * Sepsis and low perfusion states * Bacterial sepsis very often accompanied by cholestasis by hypotension and bacterial endotoxins * Congestive heart failure, reduced hepatic blood flow and the delivery of bilirubin to hepatocytes, results in predominantly unconjugated hyperbilirubinaemia * Malignancy * Paraneoplastic syndromes associated with malignancy can induce a reversible form of cholestasis (Stauffer syndrome), renal cell carcinoma, malignancy lymphoproliferative diseases, gynaecologic malignancies and prostate cancer * Liver infiltrations - infiltrative processes such as amyloidosis, lymphoma, sarcoidosis, tuberculosis can precipitate intrahepatic cholestasis

Question 35

List the symptoms associated with typhoid/paratyphoid fever

Answer 35

* GI symptoms: * Diarrhoea vs constipation * 50:50 * Diarrhoea more common in children * Abdominal pain - hepatosplenic discomfort * Rectal bleeding * Bowel perforation - hyperplasia Peyer's patches * Other Symptoms: * Neurological * Headache (44-94%) * Enteric encephalopathy (not infection) * Altered consciousness/confusion * Increased mortality * Steroids * Bacteraemia * Metastatic infection * Relative bradycardia (would expect tachycardia) * Rose spots - bacterial emboli to skin

Question 36

List the reservoirs for infections

Answer 36

* Environment * Animals * Humans * Symptomatic/asymptomatic * Carriers

Question 37

Describe the use of amoxicillin

Answer 37

* Semi-synthetic penicillin * Greatly increased activity against gram negative organisms (although resistance is now common) * Much more orally bioavailable than natural penicillins * Widely used in the treatment of many infections * Sensitivities * Streptococcus, enterococcus * Neisseria * Haemophilus, clostridium * Resistance * Rest * Often used for respiratory tract infections caused by strep/haemophilus

Question 38

Describe the toxicity of gentamicin

Answer 38

* Nephrotoxicity * Ototoxicity * Hearing and balance loss * Oscillopsia * Neuromuscular blockage - usually only significant in myaesthenia gravis * Strict prescribing to prevent toxicity

Question 39

List bacterial causes of traveller's diarrhoea

Answer 39

Enterotoxigenic E. Coli Enteroaggregative E. Coli Campylobacter sp. Salmonella sp. Shigella sp. C difficile Vibrio sp. Aeromonas Plesiomonas shigelloides Yersinia enterocolitica

Question 40

How can antibiotics cause harm?

Answer 40

* Disruption of bacterial flora leads to overgrowth of yeasts (thrush), overgrowth of bowel (diarrhoea) * Antibiotic use associated with development of C. diff colitis (in patients and those they are in contact with), future colonisation and infection with resistant organisms

Question 41

Describe the classification of streptococci

Answer 41

* Initially classified according to their ability to haemolyse blood agar * Alpha-haemolytic streptococci * S. pneumoniae - also called pneumococcus, common cause of pneumonia and meningitis * S. viridans - commonest cause of bacterial endocarditis * Beta-haemolytic streptococci * S. pyrogenes (group A strep) - can cause wound infections and local infections such as tonsillitis and pharyngitis, as well as serious systemic infections e.g. necrotising fasciitis and fulminant shock with accompanying bacteraemia secondary to infection in other sites * Gamma non-haemolytic streptococci

Question 42

Describe the antibiotic regimen used in the treatment of necrotising fasciitis

Answer 42

IV flucloxacillin IV benzylpenicillin IV metronidazole IV gentamicin IV clindamycin

Question 43

Which bacteria are sensitive/resistant to tazocin?

Answer 43

Highly sensitive - streptococcus, enterococcus, staphylococcus, E. Coli, other coliforms, neisseria, haemophilus, pseudomonas Sensitive - bacteroides

Question 44

How are ESBL infections treated? Why is this becoming more difficult?

Answer 44

* Develop a new class beta-lactam antibiotic - carbapenems * Carbapenemase now being produced - resistance * Carbapenem = broad spectrum antibiotic (related to penicillin e.g. Meropenem) * Carbapenemase = an enzyme that breaks down a carbapenem * Worrying as carbapenems viewed as the last therapeutic option to treat complex infections caused by MDR bacteria

Question 45

How are macrolides administered?

Answer 45

Excellent oral absorption - given orally even in severe infection

Question 46

Define sepsis

Answer 46

Life threatening organ dysfunction due to a dysregulated host response to infection Major cause of mortality

Question 47

Describe the use of benzylpenicillin

Answer 47

* Administered by IV route * Oral agent (penicillin V) but not often used * First choice antibiotic for serious streptococcal infection e.g. erysipelas - skin * Narrow spectrum agent * Sensitivities - streptoccocus, some neisseria, minorly clostridium * Resistant - others

Question 48

What is the commonest cause of community acquire pneumonia?

Answer 48

Streptococcus pneumoniae * Gram positive coccus, in pairs * Most common cause in all groups - old, young, immunosuppressed etc.

Question 49

What is the clinical significance of bacteroides?

Answer 49

* Can cause infections of the peritoneal cavity e.g. after gastrointestinal surgery * Resistant to many antibiotics

Question 50

What are the common causes of cellulitis?

Answer 50

Staphylococcus, streptococcus

Question 51

How can antimicrobial stewardship be incorporated into the concept of realistic medicine?

Answer 51

Reduces variation in prescribing practice Reduces waste - over Rx, redundancy Reduces harm - CDI, AMR, penicillin allergy, toxicity Allows personalisation/individualisation - risk based Rx = optimised use and outcome

Question 52

How is typhoid/paratyphoid fever treated?

Answer 52

* Quinolones * Most effective agents - ciprofloxacin most commonly used * Resistance, especially if from South/Central Asia * Cephalosporins * Empiric therapy * Longer courses (14 days) * Azithromycin * Very good activity with increasing evidence * Lack of evidence in severe disease * Oral option

Question 53

List the types of antibiotics which act by inhibiting protein synethsis

Answer 53

* 50S ribosomal subunit * Macrolides * Erythromycin * Clarithromycin * Azithromycin * Clindamycin * Chloramphenicol * 30S ribosomal subunit * Aminoglycosides * Gentamicin * Doxycyclin

Question 54

Describe the appearance of haemophilus influenzae

Answer 54

Gram negative rods

Question 55

What types of infection do carbapenem resistant enterobacteriaceae cause?

Answer 55

* Bacteriaemia * Pneumonia * UTI * Wound infections

Question 56

Describe empirical guidance in primary care

Answer 56

* Diagnosis usually syndromic and empirical * E.g. fever/pain score for bacterial throat infection * Near patient tests * CRP, GAS test, urinalysis - beware of over diagnosis * Culture * Skin - only swab infected area - limited value, reflects commensal bacteria * Urine culture - asymptomatic bacteriuria

Question 57

How can the problem of AMR be reduced?

Answer 57

1. Wash hands 2. Get vaccinated against flu 3. Improve diagnostic skills

Question 58

How can C diff infection be prevented?

Answer 58

When prescribing keep antibiotics as narrow spectrum as possible

Question 59

List the types of antimicrobial stewardship interventions used to achieve objectives, and the features of each

Answer 59

1. Persuasive * Education, feedback, reminders, specialist advice, lab reporting * Longer term benefits through behaviour change 2. Restrictive * Formulary restrictions, pre-authorisation, automatic stop, unsolicited specialist intervention * Short term benefits including reduction in resistance

Question 60

Give examples of haemophilus bacteria

Answer 60

Includes H. influenzae which causes sepsis and bacterial meningitis in young child and H. Ducreyi which causes chancroid

Question 61

Describe how an antibiotic review following empirical treatment is done in primary and secondary care

Answer 61

* Primary care * Electronic prescribing of definitive course + decision support * 'Safety netting' or review to assess response * Secondary case - assess response, review patient * Clinical, micro results * De-escalate - simplify, switch or stop * Review IV daily - IVOST/stop * Document (3 day) review * Record specific duration of Rx * Consider specialist input and source control

Question 62

How can pneumonia be differentiated from an exacerbation of COPD?

Answer 62

Consolidation on X-ray or from clinical signs = pneumonia

Question 63

List the standard infection control precautions

Answer 63

* Assess patients for infection risk and ensure they are cared for in a safe place * Practice good hand hygiene * 5 hand hygiene moments = * Before touching a patient * Before procedure * After a procedure or body fluid exposure risk * After touching a patient * After touching a patient's surroundings * Cover nose and mouth when coughing or sneezing (catch it, bin it, kill it) * Wear suitable personal protective equipment * Keep all reusable care equipment clean and well maintained * Keep the care environment clean and tidy * Safely handle used linen * Safely clean up all blood and body fluid spillages * Safely dispose of all household and care activity waste * Take corrective action if injured or exposed to blood and body fluids

Question 64

List the transmission based infection control precautions

Answer 64

* Contact - isolation, cleaning, gloves, apron * Droplet - surgical mask and eye protection * Airborne - FFP3 masks * TB * Pandemic flu * Aerosol generating procedures for respiratory pathogens * Measles varicella zoster

Question 65

Give examples of beta-lactamase inhibitors

Answer 65

* Clavulanic acid - combined with amoxicillin to make co-amoxiclav (Augmentin) * Tazobactam - combined with piperacillin to make tazocin

Question 66

What measures should be taken in a patient who is found to have a C. difficile infection?

Answer 66

* The severity of the CDI should be assessed and appropriate treatment initiated i.e. a decision made as to whether to start metronidazole or vancomycin * Unnecessary antibiotics should be stopped * Any laxatives and proton pump inhibitors should be stopped * Standard infection control precautions need to be in place as well as isolation of the patient and appropriate hand hygiene with soap and water and not alcohol gels

Question 67

Describe the typical pathogenesis of acute bacterial cholecystitis

Answer 67

Bacterial infection in a patient with biliary obstruction, organisms typically ascend from the duodenum when normal barrier mechanisms are disrupted, bacteria can pass through the sphincter of Oddi with a stone then acting as a nidus for colonisation/infection

Question 68

How can a rapidly progressing/immediately life-threatening infection be identified?

Answer 68

* Organ dysfunction = sepsis * Deep seated/involving vital organs (may not be sepsis) * Bacteraemia * CNS * Cardiovascular * Graft related * Systemic inflammatory response - fever/hypothermia, tachypnoea, tachycardia, high/low WCC

Question 69

How does surviellance underpin antimicrobial stewardship?

Answer 69

* Volume of antibiotic prescribing * Measured through pharmacy records (not per individual) * Stratified for antibiotic type (defined daily dose) * Adjusted for population size e.g. per 1000 population or per admission/occupied bed day * Quality of antibiotic prescribing * Measures prescribing in an individual against a guideline * Antimicrobial resistance * To inform guidance and monitor effect of interventions * Clostridium difficile * Other adverse events related to prescribing/interventions

Question 70

Which bacteria are sensitive/resistant to co-amoxiclav?

Answer 70

Highly sensitive - streptococcus, enterococcus, staphylococcus, neisseria, haemophilus Sensitive - E. coli, other coliforms, bacteroides, clostridium Resistant - Pseudomonas

Question 71

What are the important questions to ask when taking a history from a patient presenting with acute diarrhoea?

Answer 71

1. Food history - can they attribute the onset of diarrhoea to a particular meal they ate, classic causes include undercooked poultry, reheated rice and frozen food that has been incompletely defrosted prior to cooking 2. Ill contacts - many forms of gastroenteritis passes from person to person, particularly important when thinking about viral gastroenteritis where contact with others (often children) with diarrhoea and vomiting is common 3. Travel history - ask about pre-travel vaccination and food and water precautions when travelling (use of bottled water, ice in drinks etc.), travel to exotic locations increase risk of parasitic causes of gastroenteritis and changes the spectrum of possible pathogens 4. Past medical history - important when thinking about non-infectious aetiology, ask about medication (many drugs include diarrhoea as a side effect) 5. Occupational history - some occupations bring people into contact with potential reservoirs of infection e.g. sewage workers, vets. Important to know if they handle food - implications for when they can return to work to prevent onward transmission of any infection 6. Risk factors for C. diff infection - usually a hospital acquired infection, main risk factors are age \>65, recent hospitalisation and recent course of antibiotics (presence of 2/3 risk factors should prompt the consideration of CDI as a cause of diarrhoea)

Question 72

Describe the reservoir of and illness caused by rotavirus

Answer 72

Person to person Vomiting and non-bloody diarrhoea - most often in children

Question 73

What criteria define systemic inflammatory response syndrome?

Answer 73

2 or more of * Temperature \>38 * Tachycardia \>90bpm * Tachypnoea RR\>20/min * WBC \>12

Question 74

List antibiotics that act by targetting DNA repair and replication

Answer 74

* Quinolones * Ciprofloxacin * Levofloxacin * Rifampicin

Question 75

Which antibiotics should be prescribed, and for how long in a hospitalised COPD exacerbation with green sputum?

Answer 75

* Doxycycline or amoxicillin * 5 days

Question 76

How can the action of beta-lactamases be prevented?

Answer 76

* Beta-lactamase inhibitors - effectively inhibit some beta-lactamases * Co-administered with penicillin antibiotic * Greatly broadens spectrum of penicillins against gram -ves and S. aureus * There are many beta-lactamases that are not inhibited leading to antibiotic failure

Question 77

Describe the typical appearance of streptococci bacteria

Answer 77

Gram positive cocci, grow in chains

Question 78

Describe the minor criteria of the Duke criteria

Answer 78

* Fever - temperature \>38 * Vascular phenomena - arterial emboli, pulmonary infarcts, intracranial bleed, conjunctival haemorrhages, Janeway lesions * Predisposing heart condition (prosthetic heart valve or a valve lesion associated with significant regurgitation or turbulence of blood flow) or intravenous drug use * Immunologic phenomena - Osler nodes, Roth spots, rheumatoid factor, glomerulonephritis * Positive blood cultures but doesn’t meet major criteria or serologic evidence of active infection with organism consistent with IE

Question 79

Describe the relationship between antibiotic use and antimicrobial resistance

Answer 79

AMR correlated with human antibiotics use - countries which use more antibiotics have higher levels of AMR

Question 80

How is a rapidly progressing/immediately life-threatening infection dealt with in secondary care?

Answer 80

* Urgent blood cultures then IV antimicrobial therapy within ONE hour * Review all anatomical systems, perform CXR and consider other imaging/laboratory investigations. Review diagnosis daily. * Add cover for S. aureus infection if - healthcare associated, recent hospitalisation, post-op wound/line related, IVDU/PWID * Add cover for MRSA infection if recent MRSA carrier or previous infection * Add cover for severe streptococcal infection if pharyngitis/erythroderma/hypotension

Question 81

Describe the type 1 hypersensitivity reaction which can occur in response to beta-lactams

Answer 81

* Relatively common allergy (0.7-4% of penicillin courses) * Most patients develop an urticarial rash * Anaphylaxis is most feared complication - gross neck swelling and airway obstruction * Cross reaction between classes is variable

Question 82

Describe the appearance of E. Coli

Answer 82

Rod shaped coliform

Question 83

How long should antibiotics be prescribed for in cellulitis, and what is this determined by?

Answer 83

7-10 days, determined by response

Question 84

List the mechanisms of bacterial resistance in gram negative bacteria

Answer 84

1. Loss of porins 2. Beta-lactamases in periplasmic space 3. Over-expression of transmembrane efflux pump 4. Antibiotic modifying enzymes 5. Target mutations 6. Ribosomal mutation or modification 7. Mutations in polysaccharide structure

Question 85

What is the minimum total duration of antimicrobial therapy recommended for the treatment of septic arthritis?

Answer 85

* Optimal duration remains uncertain * Typical duration of parenteral antibiotics is at least 14 days, followed by oral therapy for an additional 7-21 days * Choice of oral antibiotic regimen for completion of therapy depends on the pathogen and antibiotic susceptibility (oral agents with high bioavailability)

Question 86

Explain the staining of gram positive and gram negative bacteria

Answer 86

* Gram positive * Stain purple - take up dye and don't release it when washed due to thick cell wall * Gram negative * Stain pink - take up dye and release it when washed due to thin cell wall

Question 87

List the causes of enteric fever (typhoid or paratyphoid)

Answer 87

* Salmonellae typhi * Salmonellae paratyphi * Human reservoir only (no animal reservoir) * Human to human * Contaminated food/water * Infectious load * 1000 organisms cause disease in 10-20% * Higher inoculum - shorter incubation period/higher attach rate * Most prevalent in South Central Asia - India, Pakistan, Nepal

Question 88

Why has the use of aminoglyosides recently increased?

Answer 88

* Improved dosing regimens * Restriction of other broad spectrum antibiotics e.g. cephalosporins * Use of gentamicin in Glasgow more than doubled

Question 89

Describe the pathogenesis of typhoid/paratyphoid fever

Answer 89

Ingest contaminated food/water Bacteria invade through Peyer's patches Infects the reticuloendothelial system - liver, spleen, lymph nodes After a period of time become bacteraemic

Question 90

Describe the appearance of emphysema on x-ray

Answer 90

* Black lungs * Diffuse hyperinflation with flattening of diaphragm * Enlargement of pulmonary artery/right ventricle

Question 91

What negative effects do mislabeling penicillin allergies have?

Answer 91

Increased Rx cost, admission length, AMR and poorer outcomes

Question 92

What AMR mechanisms have evolved in S aureus?

Answer 92

* Ab degradation - penicillinase * Target modification - PBPs (MRSA) * Antibiotic efflux - tetracycline R

Question 93

How long should antibiotics be prescribed for in upper UTIs?

Answer 93

7 days

Question 94

Describe the features of mycoplasma pneumoniae

Answer 94

* Commonest atypical pneumonia - not classical presentation * Smallest free living bacterium * Lack of cell wall, important when considering antibiotics * Very difficult to grow, other ways of diagnosing * Most prevalent in autumn/winter

Question 95

What are the confounding variables affecting resistance of a bacteria?

Answer 95

* Laboratory * Inoculum size, growth phase, planktonic, pH, atmosphere * Biofilm * Clinical * Co-morbidities, pus collections, foreign bodies, site of infections * Biofilm (e.g. on prosthetics - difficult to treat) * Pharmacokinetics * Pharmacodynamics

Question 96

How long should antibiotics be prescribed for in intra-abdominal sepsis and what is this determined by?

Answer 96

4 days, determined by if the source is controlled or not

Question 97

Describe the epidemiology of malaria

Answer 97

* 27-48% hospitalised returning travellers * Most common cause of fever in travellers from Sub-Saharan Africa (risk elsewhere) * 10% geosentinel no report of fever * GI - diarrhoea * Respiratory - dry cough * Headaches * Diagnosis initially missed in up to 59% * Rx 7.6 days after admission High Risk Areas * Sub-Saharan Africa * India, Pakistan, Southeast Asia * Americas - Amazon basin

Question 98

Describe the criteria in sequential organ function assessment

Answer 98

Respiratory rate \>30 Confused Low BP unresponsive to fluid challenge = evidence of organ dysfunction

Question 99

List viral causes of traveller's diarrhoea

Answer 99

Norovirus Rotavirus Enteric adenovirus

Question 100

Describe the reservoir of and illness caused by E. Coli 0157

Answer 100

Ruminants (beef) Bloody diarrhoea, colic, low grade fever

Question 101

What are the main points from history/examination which would suggest HIV infection in a patient with acute diarrhoea?

Answer 101

Diarrhoea is a common manifections of HIV infection - results from infection of enterocytes with HIV Will often be accompanied by weight loss and other HIV indicator illnesses e.g. previous shingles, oral thrush, thrombocytopaenia

Question 102

Describe the clinical features of typhoid/paratyphoid fever

Answer 102

* Incubation period 5-21 days * Shorter in older, those with reduced gastric acidity, immunocompromised and where there is a high infectious load * Spectrum of clinical effect * Fever, myalgia, headache, cough, abdominal pain, constipation, diarrhoea --\> septic shock, death * Mortality rates \<1% with antibiotics (15% pre-antibiotic era)

Question 103

Compare resistance against clarithromycin in typical and atypical pathogens

Answer 103

* Resistance among typical pathogens relatively common - can only be used in non-severe infections * Resistance among 'atypical' pathogens relatively rare - is included in severe infections to cover these organisms (esp. severe community acquired pneumonia)

Question 104

What is the role of the laboratory in antimicrobial stewardship programmes?

Answer 104

* Optimisation of lab diagnosis - sampling, testing and minimisation of 'over diagnosis' * Restricted reporting of organisms to prevent over treatment * Restrict reporting sensitivities to reduce use of innapropriate agents * Co-ordination of clinical advice with guidance * Data on resistance and CDI

Question 105

Give examples of gram positive rods

Answer 105

1. Clostridia (C difficile, C tetani) 2. Bacillus (B anthracis, B cereus) 3. Listeria (L monocytogenes) 4. Others - corynbacteria (C diphtheriae) and propionobacterium (P acnes)

Question 106

Why do some countries have higher antibiotic use than others?

Answer 106

In most countries, antibiotics can be easily purchased without prescription or involvement of a health profession or veterinarian Poor quality medical and veterinary products are widespread, and often contain low concentration of active ingredients, encouraging emergence of resistant microbes

Question 107

Other than AMR, what harm is caused by antibiotic overuse?

Answer 107

1. Increase in broad spectrum antibiotics (cephalosporins) correlates with rise in CDI 2. Avoidable toxicity - 1 in 5 hospital patients suffer \>1 antibiotic associated adverse event altering their clinical path * Vascular device complications (including \>50% of SABs) * Prolonged hospitalisation 3. Opportunity cost - IV antibiotics divert nursing time from patient care 4. Unnecessary prolonged Rx - wasteful and expensive

Question 108

Describe the use of flucloxacillin

Answer 108

* Synthetic penicillin developed to be resistant to beta-lactamase produced by staphlycocci * Antibiotic highly active against * Staphylococcus aureus (not MRSA) * Streptococci * No activity at all against gram negative organisms * Can be given orally but nausea limits dose

Question 109

List four important clinical signs/symptoms associated with acute septic arthritis

Answer 109

Joint pain Joint swelling Warmth Restricted movement Seen in approx. 80% patients with septic arthritis

Question 110

Describe types of Neisseria bacteria

Answer 110

* N. meningitidis - causes bacterial meningitis and septicaemia * N. gonorrhoeae - causes gonorrhoea

Question 111

In which environments is legionella pneumophila often transmitted?

Answer 111

* Free living organism * Infects amoebae, found in things that aerosolise water * Jacuzzis * Hotel showers * Air conditioning * Hospitals

Question 112

Describe the types of necrotising fasciitis and the causative organisms

Answer 112

4 classes of necrotising fasciitis * Type 1 - synergistic infection with anaerobes (e.g. bacteroides, peptostreptococcus) and aerobes (streptococci, enterobacteriaciae), more common in elderly diabetic patients - very broad antibiotic cover required * Type 2 - infection with group A streptococci (S pyrogenes or occasionally S aureus), mediated by toxin production * Type 3 - vibrio vulnificus, after trauma in sea water * Type 4 - fungal

Question 113

Describe the structure and mechanism of action of beta-lactams

Answer 113

* All beta-lactams have same structural feature - beta lactam motif, analogue of branching structure of peptidoglycan * Present analogue of peptidoglycan to enzymes which cause peptidoglycan crosslinking needed for bacterial cell wall * Inhibits crosslinking of cell wall peptidoglycan * Causes lysis of bacteria - bacteriocidal * Very fast acting

Question 114

How does bacterial gastroenteritis usually differ in onset from food poisoning caused by ingestion of toxins or viruses?

Answer 114

Food poisoning caused by ingestion of toxins or viruses tend to have an abrupt onset of symptoms within hours of ingestion Bacterial gastroenteritis tends to take longer to develop although can occur abruptly if a high amount of bacteria are ingested

Question 115

How can potential hosts be protected from infection?

Answer 115

Vaccination Prophylaxis Nutrition Treatment of immuno-suppressive Protective isolation

Question 116

Describe the mechanism of action of bactericidal antibiotics

Answer 116

* Achieve sterilisation of the infected site by directly killing bacteria * Lysis of bacteria can lead to release of toxins and inflammatory material

Question 117

What is the main issue with vancomycin in clinical use?

Answer 117

Under-dosing - cleared too fast in those with normal kidney function

Question 118

List the examples of viral haemorrhagic fever

Answer 118

* Lassa - most common, spread by rats found in grain barns in rural West Africa * Ebola/Marburg - probably same virus, spread by giant fruit bats * Now have drugs to treat * Congo-Crimean haemorrhagic fever - spread by tics * South American haemorrhagic fevers - rare * Rift valley fever * Dengue haemorrhagic fever - mosquitoes * Yellow fever

Question 119

How should a catheter associated UTI be treated?

Answer 119

* Remove catheter * Rx if symptoms/sepsis

Question 120

Describe the lifecycle of the malarial parasite

Answer 120

1. Sexual cycle completed within the gut of a female anopheles mosquito 2. Sporozoites to saliva of mosquito 3. Mosquito bites, parasite detects body heat and is released in the mosquitoes salvia, also contains a local anaesthetic to allow feeding without host awareness - sporozoites inoculated into human host 4. Preerythrotic stage in liver - schizonts 5. Schizonts rupture and parasite is liberated from the liver into the bloodstream 6. Incorporated into RBC, matures * Immature trophozoite (ring stage) * Mature trophozoite * Schizont * Ruptured schizont - spread Or become gametocytes --\> infect other mosquitoes

Question 121

Describe the mechanism of action of metronidazole

Answer 121

* Enters by passive diffusion and produces free radicals * Effective against most anaerobic bacteria - not actinomyces

Question 122

List the common antibiotic combination therapies

Answer 122

Amoxicillin + clavulanic acid = Augmentin Piperacillin + taxobactam = Tazocin

Question 123

How does human behaviour impact antibiotic prescription? How should this be challenged?

Answer 123

* GPs feel under pressure to prescribe antibiotics - will prescribe when unsure if bacterial or viral infection, when they don’t deem it medically necessary or just to appease patients * Misconceptions - withholding antibiotics is always harmful or 'wrong' * Expectations and experience drive antibiotic seeking behaviour - doctors can reinforce behaviour by prescribing antibiotics when not necessary * Evidence evolves - behaviour needs to also, keep up to date * Prescribing is multifaceted - hierarchy is bad, value all the team

Question 124

What signs would strongly suggest a bacterial infection, prompting the prescription of an antibiotic?

Answer 124

* Symptoms/signs of infection * Fever, sweats, rigors, shivers and shakes * Localising symptoms/signs * Dysuria and frequency * Dyspnoea, cough + green/brown sputum, crepitiations * Erythema, heat, swelling * Sore throat with exudate and adenopathy * Record indication for antibiotic

Question 125

How is vancomycin administered?

Answer 125

* Not absorbed from GI tract so almost always given IV * Oral route only used for treatment of C. diff * Long half-life so loading doses usually given

Question 126

How is mycoplasma pneumoniae diagnosed?

Answer 126

Difficult to culture - not done Serology PCR (sputum/throat swab/viral gargle)

Question 127

Describe the action of clindamycin

Answer 127

* Similar in many was to macrolides * Same mechanism of action * Excellent oral absorption * Principle action against gram +ves * Some key differences * No action against aerobic gram -ves or atypicals * Excellent activity against anaerobes * Highly effective at stopping exotoxin production

Question 128

How is an antimicrobial stewardship leadership team organised?

Answer 128

* Leadership - dedicated team with expertise in infection management, prescribing surveillance and quality improvement * Infection specialists, clinical pharmacist * Multi-disciplinary clinical network and committee * Management engagement and IPC coordination * Clinical governance and patient safety

Question 129

Give examples of barriers to and qualities which promote antimicrobial stewardship

Answer 129

Knowledge Experience Prescribing culture Hierarchy Team work/perception of roles and responsibilities

Question 130

What pattern can be seen in antibiotic deployment and observation of antibiotic resistance?

Answer 130

Every time a new antibiotic is discovered resistance develops Fewer antibiotics being discovered so resistance becomes a problem

Question 131

Describe the reservoir of and illness caused by giardiasis

Answer 131

Contaminated food and water Loose stool often associated with bloating and excess wind

Question 132

Which disease-causing organisms are included in the clostridium species?

Answer 132

Causative agents of botulism and tetanus e.g. C. difficile

Question 133

How can the heart and appendages be easily viewed in the diagnosis of endocarditis?

Answer 133

* Heart and appendages easily viewed by an echo * Transthoracic echo is a non-invasive procedure that define both the structure and the function of the heart, not as sensitive as transoesophageal echo, which is more invasive (patients need to be sedated)

Question 134

Define antibiotic spectrum

Answer 134

* Range of bacterial species treated effectively by the antibiotic * Can vary widely even within the same antibiotic class e.g. Penicillins have no overlap in spectrum * Important to distinguish between lack of activity and resistance * Lack of activity - intrinsically the antibiotic won't have any effect due to the nature of the bacterium * Resistance - bacterium has acquired an often genetic factor which prevents the antibiotic having an effect

Question 135

What is the advantage of cephalosporins over penicillins?

Answer 135

Less susceptible to beta-lactamases Good activity against gram -ves and gram +ves

Question 136

Describe the appearance of staphylococci bacteria

Answer 136

Gram positive coccus, grow in irregular grape-like clusters

Question 137

What are the most common causes of gastroenteritis in patients with no past medical history, no regular medication and no travel history?

Answer 137

Campylobacter sp. Salmonella sp. E. Coli 0157 Norovirus Rotavirus Giardiasis Enterohaemorrhagic E. Coli

Question 138

Give examples of gram negative rods

Answer 138

1. E coli 2. Klebsiella (K pneumoniae) 3. Pseudomonas (P aeuroginosa) 4. Others - proteus, serratia, salmonella, shigella etc.

Question 139

When is doxycycline commonly used?

Answer 139

Soft tissue infections, respiratory tract infections (if allergic to amoxicillin) Travel associated atypicals, anti-malarials

Question 140

Give an example of how conjugation gives a bacterium resistance

Answer 140

Example of Conjugation and Beta Lactamases: * AMR mechanism = antibiotic degradation * Beta-lactamases in Enterobacteriaceae

Question 141

List the causes of conjugated hyperbilirubinaemia

Answer 141

* Biliary obstruction (extrahepatic cholestasis) * Both conjugated and unconjugated bilirubin accumulate in serum * Intrahepatic cholestasis * Hepatocellular injury

Question 142

Where are clostridium bacteria usually found?

Answer 142

Lower reproductive tract of women

Question 143

What would the immediate management plan for necrotising fasciitis be?

Answer 143

* Immediate action must be taken * Patient requires an urgent surgical/plastics/orthopaedics review for wide debridement of all the infected tissue * Tissue from theatre should be sent to microbiology urgently for gram stain and culture * IV antibiotics important at this stage, unlikely to work whilst the necrotic tissue is present - avascular and full of organisms * Very broad cover needed, common combination is IV flucloxacillin (for gram -ves), IV benzylpenicillin (for streptococci), IV gentamicin (for gram negatives), IV metronidazole (for anaerobes) and PO/IV clindamycin (for anaerobes/reduction in toxin production) * If he was penicillin allergic/MRSA positive, vancomycin should be used * Discuss with microbiology or ID for advice * Hypotensive - require IV fluids rapidly, and catheterisation for monitoring of urine output * Should contact ITU, will have to go there post-op, and the anaesthetist will be able to give advice (may require inotropic support and a central line for access and monitoring CVP) * IV immunoglobulin could be considered, but there is a risk of anaphylaxis and the evidence base is lacking

Question 144

Describe the appearance of clostridium bacteria

Answer 144

Obligate anaerobes producing endospores, rod shaped

Question 145

Describe antibiotic treatment in biliary sepsis

Answer 145

* Enteric flora - particularly gram -ve bacilli such as E.coli, Klebsiella spp. and enterobacter spp., gram positive bacteria such as enterococci and anaerobes such as bacteroides and clostridia * Appropriate empiric combinations may include: * Gentamicin, amoxicillin and metronidazole (issues with aminoglycosides and renal toxicity esp. in elderly) * Gentamicin and co-amoxiclav (issues w/ C diff and co-amoxiclav) * Piperacillin-tazobactam and gentamicin (broader gram -ve cover, covers anaerobes and most enterococci) * Ceftriaxone/cefotaxime and metronidazole (C. diff, lack of enterococcal cover) * Carbapenem (meropenem/imipenem) where history of infections with more resistant organisms e.g. ESBL producing coliforms - especially in those with recurrent biliary sepsis, prior biliary tract surgical procedures and with biliary-intestinal anastomoses * Treatment should not only be 'supportive' with appropriate antimicrobial therapy but must include investigation to identify possible obstruction of the biliary tree with subsequent decompression/drainage if required

Question 146

What is antimicrobial resistance?

Answer 146

Antimicrobial resistance occurs when microorganisms such as bacteria, viruses, fungi and parasites change in ways that render the medications used to cure the infections they cause ineffective Global problem - treatment options limited, global consumption up, overuse and misuse leads to harm

Question 147

What are the features of empirical antibiotic guidelines?

Answer 147

* Appropriate for target population * Primary vs secondary care, specialist vs generalist * National vs local adaptation * Key components * Decision support - when to avoid/use antibiotics (and how) * Appropriate investigations to support management * Takes into account epidemiology of infection including AMR * Population and individual risk of C. diff * Availability/cost * Specifics of antimicrobial prescribing * Choice, dose, route of admin, duration, severity assess, TDM

Question 148

Describe the reservoir of and illness caused by enterohaemorrhagic E. Coli

Answer 148

Contaminated food and water Loose stool, nausea and colic in travellers (traveller's diarrhoea)

Question 149

Describe the reservoir of and illness caused by campylobacter sp.

Answer 149

Poultry Loose stool and nausea, colic, sometimes bloody stool

Question 150

How prevalent are healthcare acquired infections?

Answer 150

7-10% of every 100 hospitalised patients, 7 in high-income and 10 in low and middle-income countries, will acquire at least one healthcare-associated infection. 1/4 of these will be antibiotic resistant.

Question 151

What causes re-emergence of old diseases/appearance of new diseases/antibiotic resistance?

Answer 151

Multifactoral: * New patterns of travel (air) and trade (especially food) * Developments in agricultural practices/animal husbandry * Sexual behaviour * Medical interventions/developments in medical technology * Increases populations at extremes of age * Over/unnecessary use of antibiotics * The breakdown of economic, social and political systems

Question 152

How is Dengue fever transmitted?

Answer 152

Aedes mosquito - most common mosquito borne virus

Question 153

Describe the action of gentamicin

Answer 153

* Reversibly binds to 30S ribosome * Bacteriostatic action * Results in prolonged post-antibiotic effect * Poorly understoof action on the cell membrane * Bactericidal action * Prominent at high concentrations * Results in rapid killing early in dosing interval

Question 154

How long should antibiotics be prescribed for in community/hospital acquired pneumonia (mild-severe)

Answer 154

5 days

Question 155

How is legionella pneumophila treated?

Answer 155

* Intracellular - can't use beta lactams (penicillins/cephalosporins) * Macrolides (clarithromycin) * Quinolones (ciprofloxacin) * Tetracyclines (doxycyline)

Question 156

What surgical prophylaxis should be given to an MRSA colonised patient in an emergency situation?

Answer 156

A glycopeptide e.g. vancomycin or teicoplanin

Question 157

Describe the methods of antibiotic therapy

Answer 157

* Guided therapy - depends on identifying cause of infection and selecting agent based on sensitivity testing * Empirical therapy - best (educated) guess therapy based on clinical/epidemiology acumen, used when therapy cannot wait for culture (or if it is not practical to take a culture) * Prophylactic therapy - preventing infection before it begins

Question 158

How should traveller's diarrhoea be managed?

Answer 158

* Fluid replacement * Antibiotics (reduce duration by 24hrs) - not usually indicated, in developing countires spreading antibiotic resistance through antibiotic waste into open sewage systems * Quinolones * Azithromycin * Antimotility agents - caution * Diarrhoea is a physiologyical mechanism to get the organism out of the gut, antimotility agents reduce this * Can be used for symptomatic relief if needed * Investigations for other causes if long duration

Question 159

What initial radiology investigations should be performed in all patients with suspected acute cholangitis/biliary sepsis?

Answer 159

* Transabdominal ultrasound or abdominal CT scan, to look for common bile duct dilatation/stones * USS has a high specificity for detection of stones but lower sensitivity for detecting bile duct dilatation * CT has high sensitivity in detection of bile duct dilatation and can identify biliary stenosis but has a lower sensitivity for bile duct stones

Question 160

How is malaria treated?

Answer 160

* Artemether compounds e.g. Riamet * Quinine and Doxycycline * Quinine has bad side effects - nausea, headache

Question 161

Describe the appearance of enterococci bacteria

Answer 161

Gram positive coccus, often occur in pairs or short chains

Question 162

Which bacteria are sensitive/resistant to ciprofloxacin?

Answer 162

Highly sensitive - E. coli and other coliforms, neisseria, haemophilus, pseudomonas Sensitive - staphylococcus, streptococcus Resistant - enterococcus, clostridium, bacteroides Atypicals also sensitive - legionella, mycoplasma, coxiella, chlamydia, chlamydophia

Question 163

Describe the toxicity of metronidazole

Answer 163

* Causes unpleasant reaction with alcohol * Antabuse - inhibits alcohol metabolic pathway, acetaldehyde builds up * Peripheral neuropathy with long term use

Question 164

Give examples of second line agents for short course tuberculosis therapy

Answer 164

Quinolones and aminoglycosides

Question 165

Define resistance

Answer 165

* Defined from a biological perspective - national variations in breakpoints * Resistance definitions usually based on in-vitro quantitative testing bacterial suspensions to antibacterial agents * Based on minimum inhibitory concentration * Breakpoint - concentration of antibiotic which defines whether a species is sensitive or resistant * Defined from a clinical perspective * Clinical resistance - when infection is highly unlikely to respond even to maximum doses of antibiotics (EUCAST)

Question 166

Describe the action of quinolones

Answer 166

* Broad spectrum, bactericidal antibiotics * Ciprofloxacin - good against gram -ves, weaker against gram +ves, commonly used in UTIs/abdominal infection * Levofloxacin - sacrifices some gram -ve activity for stronger gram +ve action - respiratory tract infections * Active against many 'atypical' pathogens including legionella

Question 167

How should an uncomplicated UTI (cystitis) be treated? Why?

Answer 167

* 30% of cystitis is culture negative * Majority of infection is self-limiting * NSAIDs may be as effective as Abx in symptom control * Consider delayed Abx * If prescribing Abx - trimethoprim or nitrofurantoin

Question 168

List the beta-lactamases which effect beta-lactam antibiotics

Answer 168

* Penicillins inactivated by penicillinase * Penicillinase resistant antibiotics inactivated by beta-lactamase * Cephalosporins inactivated by extended spectrum beta-lactamase - secreted by enterobacteriaceae * Generations of cephalosporins designed to be resistant to beta-lactamases

Question 169

Compared the structure of gram negative and gram positive bacteria

Answer 169

* Gram positive * Cell membrane * Peptidoglycan cell wall - very thick, more structured * Gram negative * Cell membrane * Peptidoglycan cell wall - thin * Outer membrane * Periplasm

Question 170

Describe the features of Dengue haemorrhagic fever

Answer 170

* \<1% infections * Spectrum of illness, breakbone --\> haemorrhagic * Definition * Increased vascular permeability * Thrombocytopaenia * Fever * Bleeding * Bleeding through mucous membranes - haemoptysis, haematemesis * Less likely in travellers * People infected with multiple types of Dengue fever one after the other - immune system can't cope --\> Dengue haemorrhagic fever

Question 171

How should pneumonia be managed?

Answer 171

A - Airway (conscious level?) B - Breathing (oxygen, ITU) C - Circulation (shock? - fluids?) Antibiotics - IV or Oral? Admission to hospital? * CURB65 - mortality increases with score 2+ * Sepsis - qSOFA score * Hypoxia?

Question 172

Give an example of how transformation gives a bacterium resistance

Answer 172

Example of transformation and penicillin R: * AMR mechanism = target modification * Example - change penicillin binding proteins, leads to penicillin resistance in pneumococci * Penicillin binding proteins are part of peptidoglycan bridge - target for antibiotics * Bacteria change shape of penicillin binding proteins - beta-lactams can't bind, resistance develops

Question 173

How is aztreonam administered?

Answer 173

Only given IV - no oral absorption

Question 174

What measures can be used when not prescribing an antibiotic?

Answer 174

* Mainly applicable in primary care * Reassurance/explanation * Printed information * Symptomatic measures: fluids, analgesia * Delay script * Review date/opportunity - 'safety netting'

Question 175

How are quinolones administered?

Answer 175

Excellent oral bioavailability - can use oral dosing even in severe infection

Question 176

How is typhoid/paratyphoid fever diagnosed?

Answer 176

* Travel history * Area visited * Food and drink * Pre-travel vaccination/advice * Vaccine only 75% effective * Blood culture * 60-80% positive * Don’t wait till they have a fever * Stool culture * 30% positive * Serology * Poor sensitivity/specificity - don’t use

Question 177

What are the benefits of antimicrobial stewardship in Scotland?

Answer 177

Associated with: * Reduction in broad spectrum antibiotics * Reduction in total antibiotics use in primary care * Reduction in C. diff * Reduction in MRSA * Reduction in GNB mortality * Reduction in AMR in gram negative bacteraemia

Question 178

When should IVOST be considered?

Answer 178

Clinical improvement + oral route available + uncomplicated infection --\> IVOST

Question 179

Describe the management of a patient with acute gastroenteritis

Answer 179

1. Rehydration * Most important aspect of management * Most complications result from dehydration * Depending on clinical condition and ability to take oral fluids may need to be done using IV fluids 2. Antibiotics * Not indicated in bacterial causes of gastroenteritis * Patients with significant co-morbidity or prolonged symptoms - can shorten duration of diarrhoea * Usually use quinolones (e.g. ciprofloxacin), needs to be justified because of the risk of C. diff infection 3. Infection control * Most causes transmissible from person to person, important that patients are instructed to be careful about hand washing * Identify if patient is food handler as restrictions may apply to when they can safely return to this

Question 180

What needs to be considered when a patient with acute gastroenteritis begins to improve clinically?

Answer 180

* Decisions regarding discharge depend on clinical condition * Patient should be advised regarding good hand hygiene to prevent spread to other persons within the house * Antibiotics still not routinely recommended and may prolong carriage of the organism * Public health will be notified by the laboratory of the positive result and an environmental health officer will contact the patient to discuss risk factors for the infection * Should not return to work if handling food until symptom free for 48hrs

Question 181

How do bacteria acquire resistance genes?

Answer 181

* Intrinsic resistance * Normally chromosome encoded - part natural makeup of bacteria * Resistance gene in plasmid - easily transferrable * Extrinsic resistance - transduction, transformation, conjugation * Transduction = DNA packaged in a bacteriophage infects the recipient bacterium and becomes incorporated into the recipient DNA * Transformation = transfer of genetic material takes place from donor to recipient bacterium through the liquid medium, bacterium takes up extracellular donor DNA * Conjugation - transfer of genetic material from one cell to another through direct contact or bridge-like connect

Question 182

Describe the types of mosquitoes and diseases they carry

Answer 182

* Aedes mosquito * Yellow fever, Dengue fever * Have their bum on the ground when feeding * Day biter, will also occasionally bite in the evening * Anopheline mosquito * Malaria * Have their bum in the air when feeding * Tend to feed nocturnally * Lay eggs in water, mosquito borne illnesses higher risk around water

Question 183

What are the systemic complications associated with infective endocarditis?

Answer 183

* Septic emboli - infarction of kidneys, spleen and other organs, pulmonary emboli in patients with concomitant right-sided endocarditis * Cardiac complications (up to 50%) - valvular insufficiency, heart failure * Neurological complications (up to 40%) - embolic stroke, intracerebral haemorrhage, brain abscess * Metastatic infection - osteomyelitis, septic arthritis, splenic or psoas abscess * Systemic immune reaction e.g. glomerulonephritis

Question 184

Describe the major criteria of the Duke criteria

Answer 184

* Positive blood cultures * Typical microorganisms consistent with IE from two separate blood cultures (staph aureus, strep viridans, staph gallolyticus, HACEK, enterococci) taken \>12 hours apart * HACEK - haemophilus, aggregatibacter, cardiobacterium, eikenella, kingella * Persistently positive blood cultures - if from organisms which are more commonly skin contaminants, 3 or a majority of \>4 separate blood cultures (with first and last drawn at least one hour apart) * Single positive blood cultures for coxiella burnetii or phase I IgG antibody titer \>1:800 * Evidence of endocardial involvement * Echocardiography positive for IE, vegetation (oscillating intracardiac mass on a valve or on supporting structures, in the path of regurgitant jets or on implanted material, in the absence of an alternative anatomic explanation) * Abscess * New partial dehiscence of prosthetic valve * New valvular regurfiation (increase or change in prexisting murmur is not sufficient)

Question 185

Describe charcot's triad

Answer 185

Describes the clinical presentation of acute cholecystitis: * Fever * Abdominal pain * Jaundice Approximately only 50-70% of patients have all three findings

Question 186

Define antimicrobial/antibiotic stewardship

Answer 186

* Systemic approach to safe and effective use of antibiotics - optimising outcome, minimising harm and preserving future therapies = taking care of antibiotics * Antimicrobial stewardship achieved through * Monitoring/surveillance * Guidelines/protocols * Specific restrictions (reporting/Abx) * Specific interventions * Multidisciplinary working

Question 187

What is the most common bacterial cause of septic arthritis in an adult?

Answer 187

* Staphylococcus aureus most common * Less common - streptococci (strep. Pneumoniae) * Septic arthritis due to gram negative bacilli typically occurs in older adults, in patients with underlying immunosuppression, or intravenous drug users, or as complication of trauma

Question 188

List the most common bacteria isolated in acute cholecystitis/biliary sepsis

Answer 188

* Gram negative organisms * E coli (50%) * Klebsiella species (20%) * Enterobacter species (10%) * Gram positive organisms * Enterococcus (approx. 10-20%) * Anaerobes, such as bacteroides and clostridia species are typically presented and involved in polymicrobial infection, but their frequency is likely to be underestimated by standard culture techniques

Question 189

What criteria is used to diagnose infective endocarditis?

Answer 189

Modified Duke criteria

Question 190

Where are Neisseria usually found?

Answer 190

Colonies mucosal surfaces

Question 191

What is the main issue with the antibiotics used in tuberculosis therapy?

Answer 191

Hepatoxicity - rare but can be serious

Question 192

List the important predisposing risk factors for infective endocarditis

Answer 192

* Age \>60 years * More likely to develop degenerative valve disease and require valve replacement, both are associated with increased risk of IE * Male * Intravenous drug use * Risk associated with bloodstream seeding with skin flora, oral flora and/or organisms contaminating the drug or materials used for injection * Some illicit drugs may induce valvular endothelial damage, predisposing to infection * Poor dentition or dental infection/procedures * Structural heart disease/valvular heart disease/congenital heart disease

Question 193

What is the major adverse effect of clindamycin?

Answer 193

* Excellent activity against anaerobes means clindamycin particularly effective at disrupting colonic flora * Became notorious for causing C. difficile - now understood that all antibiotics can cause CDI

Question 194

Describe the action of macrolides

Answer 194

Good spectrum against gram +ves and respiratory gram -ves Also active against atypicals - legionella, mycoplasma, chlamydia etc.

Question 195

List the possible portals of entry of infections

Answer 195

* Respiratory tract * Mucous membranes * Skin - non-intact * Mouth (faecal-oral route)

Question 196

Who needs to be informed if a patient dies as a result of C. diff infection?

Answer 196

* The procurator fiscal should be informed as the patient has died as a direct result of a Hospital Acquired Infection (HAI) * It is good practice to inform the patient's GP that the patient has died * The infection control team should also be made aware that the patient has died as a result of CDI - may already know * If the patient has been severely mismanaged and has died as a direct consequence of an avoidable HAI, the medical director should be informed as there may be issues regarding the competence of the doctors who were looking after the patient which need urgently addressed

Question 197

Describe the standard short course therapy for tuberculosis

Answer 197

* Isoniazid * Bactericidal to fast growing mycobacteria * Causes hepatotoxicity, peripheral neuropathy, B3 deficiency prevented with pyridoxine * Rifampicin * Bactericidal against slowly replicating organisms in necrotic foci * Liver, bone marrow and renal toxicity - relatively uncommon * Pyrazinamide * Bactericidal, even against slow growing mycobacteria intracellularly * Principle toxicity is hepatic, also causes arthralgia * Ethambutol * Bacteriostatic against slow growing mycobacteria * Principle toxicity is optic neuritis, watch for loss of colour vision

Question 198

How is the Duke criteria used to diagnose infective endocarditis?

Answer 198

Diagnosis of infective endocarditis: * 2 major criteria * 1 major and 3 minor * 5 minor Possible IE - 1 major + 1 minor or 3 minor

Question 199

In a patient showing signs of severe sepsis, what are the top priorities for immediate treatment?

Answer 199

* Must establish IV access, commence fluid resuscitation and start appropriate antibiotics all within the next hour * Other investigations such as routine blood tests, blood cultures and a joint aspirate are very important in diagnosis * Need to resuscitate patient and initiate effective antibiotic treatment * High risk of dying if delay and septic shock is a medical emergency

Question 200

How does the structure of gram positive/negative bacteria affect their susceptibility to antibiotics?

Answer 200

* Gram positive - thick peptidoglycan wall * Can protect self from outside hazards * Can't control what comes into contact with cell wall * Gram negative - thin peptidoglycan wall, outer membrane and periplasm * More control over what accesses the cell wall - better at developing resistance mechanisms

Question 201

List the strategies to prevent healthcare associated infection

Answer 201

Isolation Screening Cohorting Standard and transmission based precautions Surveillance Antimicrobial stewardship

Question 202

What clinical history suggests necrotising fasciitis?

Answer 202

Disproportionate pain initially NSAID use Mild preceding trauma SIRS/sepsis Rapid progress over several hours Dusky discolouration

Question 203

Why is flucloxacillin not an appropriate empirical agent in suspected MRSA infection?

Answer 203

Flucloxacillin has no activity against MRSA

Question 204

What does the evidence suggest about the ideal length of an antibiotic course?

Answer 204

Shorter antibiotic course better, once clinically better from acute bacterial infection don't need to finish long course, shorter therapy associated with less harm

Question 205

Describe the drug interactions of rifampicin

Answer 205

* Potent CYP450 enzyme inducer * Most drugs that undergo hepatic metabolism affected * Important to look up interactions when starting

Question 206

Describe the clinical presentation of legionella pneumophila

Answer 206

Atypical Non-specific - fever, malaise, myalgia Consolidation on examination/imaging

Question 207

What antibiotics should generally be used for non-severe infections (community or hospital)?

Answer 207

* Use narrow spectrum agents * Lower respiratory tract - amoxicillin or doxycycline * Lower UTI - trimethoprim or nitrofurantoin * Mild cellulitis - flucloxacillin or doxycycline

Question 208

How is Dengue fever managed?

Answer 208

Symptomatic management only

Question 209

List the steps in antibiotic prescribing

Answer 209

Is an antibiotic required? If yes - Which antibiotic? Administer IV or oral? Dose/interval (check renal function) Adjunctive measures? E.g. surgery for source control Duration and IVOST (IV-oral antibiotic switch therapy)? Review Is an antibiotic required?

Question 210

How can type 1 and type 4 penicillin hypersensitivity be distinguished?

Answer 210

Immediate (\<1 hour) = type 1 Delayed (blistering rash and systemic illness) - type IV

Question 211

Describe cross reactivity between antibiotics in beta-lactam allergies

Answer 211

* Patients allergic to a penicillin will usually be allergic to other penicillins * Cross reactivity with other antibiotic classes is much lower * Some patients with penicillin allergy may be safely managed with other beta-lactams * Particularly important if patient presents with life-threatening infection (esp. meningitis)

Question 212

Why is the development of new antibiotics so challenging?

Answer 212

* New antibiotics need to combat resistance * New antibiotics are reserved to guard against resistance * It can take in excess of 10 years from discovery to launch, estimated cost $1 billion to bring a new drug to market * Therefore: * Company develops a new agent * Use is restricted - antibiotic 'put on shelf' * Company gains minimal income and discontinues antibiotic discovery and development * Fewer new antibiotics developed * Problem worsens

Question 213

What antibiotic therapy is appropriate for treating intra-abdominal sepsis?

Answer 213

Combination of amoxicillin, gentamicin and metronidazole

Question 214

What are the common clinical signs and symptoms of infective endocarditis?

Answer 214

* Fever in up to 90%, associated with chills, anorexia and weight loss * Malaise, myalgias, arthralgias, night sweats * Dyspnoea * Cardiac murmurs (in approx. 85%) * Splenomegaly * Cutaneous manifestations - petechiae * Splinter haemorrhages Relatively uncommon clinical manifestations highly suggestive of IE include: * Janeway lesions - nontender erythematous macules on the palms and soles of feet * Osler nodes - tender subcutaneous nodules on pads of fingers and toes, thenar and hypothenar eminences * Roth spots - exudative, oedematous haemorrhagic retinal lesions

Question 215

Which bacteria are sensitive/resistant to gentamicin?

Answer 215

Highly sensitive - E. coli and other coliforms, pseudomonas Sensitive - staphylococcus Minimally sensitive - streptococcus, haemophilus, neisseria Resistant - enterococcus, clostridium, bacteroides

Question 216

Describe the reservoir of and illness caused by Norovirus

Answer 216

Person to person, nosocomial (hospital acquired) Nausea and vomiting with loose stool

Question 217

List infectious diseases which cause significant mortality globally

Answer 217

* Lower respiratory infections * HIV * Diarrhoeal diseases * TB * Malaria * Measles * Hepatitis B

Question 218

List the signs and symptoms of Scarlet fever

Answer 218

* Symptoms * Sore throat * Headache * Neck pain * Fever * Signs * Erythrodermic rash * Red back of throat * Strawberry tongue with prominent papillae * Tachycardic * Hypotensive * High respiratory rate

Question 219

When is clindamycin used?

Answer 219

Added to patients with gram +ve toxin mediated disease e.g. toxic shock syndrome, necrotising fascitis Soft tissue infections - drug use/surgical wounds

Question 220

Where are enterococci usually found?

Answer 220

Usually present in the bowel and gut

Question 221

Define sepsis

Answer 221

* Life-threatening organ dysfunction which occurs as a result of a dysregulated host response to an infection * Quantified by an increase in the sequential organ failure assessment (SOFA) score of \>2 for the organ in question * Or quick SOFA = confusion or hypotension or tachypnoea

Question 222

In which infections is aztreonam the antibiotic of choice?

Answer 222

Used in gram -ve respiratory tract infections e.g. bronchiectasis caused by pseudomonas

Question 223

List the adverse effects of clarithromycin

Answer 223

* Diarrhoea and vomiting * QT prolongation - sudden death * Hearing loss with long term use

Question 224

How should the antibiotics used to treat pneumonia be prescribed?

Answer 224

* Use Empirical Antibiotic Therapy Guidelines * More severe - broader cover, macrolide and beta-lactam * If mild probably pneumococcal, better to use narrower spectrum

Question 225

How long should antibiotics be prescribed for bone-joint infection and what is this determined by?

Answer 225

\>42 days, source control

Question 226

List the typical and atypical causative organisms of bacterial pneumonia

Answer 226

Typical - * Streptococcus pneumoniae * Haemophilus influenzae * Moraxella catharralis * Usually occurs in those with disturbed lung architecture e.g. COPD Atypical - * Mycoplasma pneumoniae * Legionella pneumoniae * Chlamydophila pneumoniae * Chlamydophila psittaci * From parrots, very rare

Question 227

Give an example of how transduction gives a bacterium resistance

Answer 227

* Tetracycline R and transduction * AMR mechanism = drug efflux * Phage gene transfer - genes for efflux pumps transferred to E. coli and salmonella, gives resistance against tetracycline R

Question 228

Describe the use of carbapenems

Answer 228

* Ultra-broad spectrum beta-lactam antibiotics developed during search for beta-lactamase inhibitors * Excellent spectrum of activity against gram +ve and -ves * No activity against MRSA * Resistant to beta-lactamases * New beta-lactamases are emerging which lyse carbapenems

Question 229

List the possible mechanisms of action of antibiotic agents

Answer 229

1. Bactericidal 2. Bacteriostatic

Question 230

How do you determine the source of bacteraemia in positive blood culture results?

Answer 230

* May get clues from history, findings on examination and type of organism isolated * May need further investigations * If treat with short-term antibiotics it may resolve temporarily, but then recur if the source has not been identified and treated

Question 231

List the indications for IV antibiotic therapy

Answer 231

* Sepsis syndrome, SIRs or rapidly progressing infection * Special conditions * Infective endocarditis * CNS infection * Bacteraemia (S. aureus) * Osteomyelitis (initially) * Mod-severe skin and soft tissue infection * Infection and oral route compromised * No oral formulation of antibiotic available

Question 232

List the main classes of infection causing bacteria

Answer 232

* Gram negative * E. coli * Other coliforms * Neisseria * Haemophilus * Pseudomonas * Gram positive * Streptococcus * Enterococcus * Staphylococcus * Anaerobes - gram positive and negative * Clostridium * Bacteroides

Question 233

Describe the toxicity and therapeutic problems associated with quinolones

Answer 233

Toxicity: * GI toxicity * QT prolongation * Tendonitis - high dose/prolonged therapy esp. * Worry about Achilles tendon rupture Other therapeutic problems: * Resistance emerging on therapy/tendon damage * C. diff infection (esp. in North America)

Question 234

How long should antibiotics be prescribed for in infective endocarditis and what is this determined by?

Answer 234

\>42 days, determined by complexity

Question 235

Which beta-lactams are safe in penicillin allergy?

Answer 235

Aztreonam (monobactam) has no cross reactivity to penicillin so can be given to those with penicillin allergy (except anaphylaxis)

Question 236

What are the main points from history/examination which would suggest diverticular disease in a patient with acute diarrhoea?

Answer 236

Often older patients with a history of alternating constipation and diarrhoea Diverticulae can become impacted with faeces leading to localised infection, so called 'diverticulitis'

Question 237

List the uses of antibiotics

Answer 237

* Treat infections * Used in majority of surgical procedures * Implant surgery (orthopaedic, vascular etc.) * Cancer surgery * Cardiac, neurosurgery * Cancer chemotherapy * Immunotherapy * Organ transplant

Question 238

What investigations should be done in suspected pneumonia?

Answer 238

* Blood tests * FBC * U&Es * ABGs/oxygen sats * Microbiology * Blood cultures * Sputum culture * Throat swab * Urine legionella antigen * Investigations * Chest X-ray * ECG

Question 239

List the aspects of bacteria that can be targetted by antibiotics

Answer 239

1. Cell wall peptidoglycan (approx 50% of antibiotics) 2. Metabolism - anti-metabolites interfere with metabolic processes in bacteria 3. Ribosome - critical for bacteria protein production 4. DNA - esp. replication and repair

Question 240

How are CREs transmitted?

Answer 240

* Routes for patients * Direct contact through carriage of CRE on hands of HCWs * Indirectly via contaminated environmental surfaces or shared equipment

Question 241

List conditions that give rise to the carriage of resistant bacteria

Answer 241

* Poor hygiene and sanitation * Overuse of antibiotics in livestock and fish farming * Over-prescription of antibiotics * Poor infection control in healthcare settings * Absence of new antibiotics being discovered * Antibiotic waste polluting rivers

Question 242

What three key investigations are recommended to diagnose septic arthritis?

Answer 242

Blood cultures Imaging - X-ray, CT Joint aspirate - for microscopy and culture

Question 243

Describe the epidemiology of bacterial pneumonia

Answer 243

5-11 per 1000 population Highest in very young and elderly 22-42% patients admitted to hospital Mortality of 8-14% (30% in ITU)

Question 244

How long should antibiotics be prescribed for in staph aureus bacteraemia and what is this determined by?

Answer 244

\>14 days, determined by source control

Question 245

What are the main points from history/examination which would suggest bowel cancer in a patient with acute diarrhoea?

Answer 245

Often older persons with altered bowel habit Weight loss may be prominent

Question 246

Which bacteria are sensitive/resistant to vancomycin?

Answer 246

Highly sensitive - staphylococcus, enterococcus, streptococcus, clostridium Resistant - E. coli, other coliforms, neisseria, haemophilus, pseudomonas, bacteroides

Question 247

Give examples of highly prevalent minor infections which significantly impact healthcare in the UK

Answer 247

* UTIs * Respiratory tract infections * Skin infections * Infectious intestinal disease * Healthcare associated infection e.g. MRSA/C. diff

Question 248

Describe the differences in generations of cephalosporins

Answer 248

1st, 2nd, 3rd, 4th and MRSA active Gram negative spectrum increases with each generation, some loss of gram positive activity Recent introduction of MRSA active cephalosporins

Question 249

List the causes of unconjugated hyperbilirubinaemia

Answer 249

* Overproduction of bilirubinDyserythropoiesis e.g. Sickle cell disease * Incorporation of haemoglobin into erythrocytes is defective, leading to degradation of a large fraction of unincorporated haemoglobin * Reduced bilirubin uptake * Impaired bilirubin conjugation

Question 250

Where is E. Coli usually found?

Answer 250

Usually found in the lower intestine

Question 251

Which bacteria are sensitive/resistant to Levofloxacin?

Answer 251

Highly sensitive - streptococcus, staphylococcus Sensitive - E. coli and other coliforms, neisseria, haemophilus, pseudomonas Resistant - clostridium, bacteroides, enterococcus Atypicals also sensitive - legionella, mycoplasma, coxiella, chlamydia, chlamydophia

Question 252

What should be included in a history taken from a returning traveller?

Answer 252

* What pre-travel advise did you receive (if any)? * Vaccines * Prescribed medications - did they actually take them? * E.g. anti-malarials * Where did you go? * Country/countries visited * Urban/rural stay within countries * How did you travel? * Planes, boats, public transport etc. * How long did you travel for? * Longer stay more likely to be exposed to local pathogens * Some illnesses present soon after travel * What did you do? * Activities in water? - Schistosomiasis * Sexual history * Co-morbidities * Might have missed medication while travelling, chronic illnesses can de-stabilise

Question 253

Which antibiotics should be used in a rapidly progressing/immediately life-threatening infection where the source is unknown?

Answer 253

* IV amoxicillin 2g 6hrly * + IV gentamicin (max 3-4 days) * If S. aureus suspected add IV flucloxacillin 2g 6 hrly * If MRSA suspected or true penicillin/beta-lactam allergy - IV vancomycin + IV gentamicin * If severe streptococcal infection suspected add IV clindamycin 600mg 6 hrly * Duration - review with response/micro results at 72 hours

Question 254

What is the antibiotic of choice in a patient who is severely unwell with a UTI?

Answer 254

* Amoxicillin and gentamicin * No issue of resistance with gentamicin and going into hospital anyway so can be administered IV * Amoxicillin - could be another infection rather than a UTI if very unwell and elderly

Question 255

Describe the potential adverse effects of beta-lactams

Answer 255

* GI toxicity * Nausea and vomiting * Diarrhoea * Cholestasis * Infection * Candidiasis - oral, vulvovaginal * Clostridium difficile infection * Selection of resistant bacteria * Hypersensitivity * Type 1 - urticaria, anaphylaxis * Type 4 - mild to severe dermatology * Interstitial nephritis * Miscellaneous rare reactions * Seizure * Haemolysis * Leucopenia

Question 256

List the modes of transmission of infection

Answer 256

* Direct * Direct contact * Droplet spread * Indirect * Airborne * Vehicle borne (food water fomites) * Vector borne (mechanical or biologic)

Question 257

What is the differential diagnosis of an erythematous swollen leg which is tender to touch, with systemic symptoms of infection?

Answer 257

Cellulitis Necrotising fasciitis Trauma - haematoma (systemic symptoms make this less likely) Myositis Osteomyelitis DVT (unlikely in active young patient) Abscess - IVDU? Erythema nodosum - nodules, underlying autoimmune disease, TB, EBV etc.

Question 258

What are the main points from history/examination which would suggest sepsis in a patient with acute diarrhoea?

Answer 258

Results from shunting of blood away from splanchnic circulation Be aware of the presence of SIRS criteria and look for other sources of infection (pneumonia, strep throat, meningitis, cellulitis)

Question 259

Why is tuberculosis difficult to treat? How is this overcome?

Answer 259

* Slow growing, high bacterial burden, limited acess of drugs to granuloma (no vascular supply) * Solution - prolonged courses of therapy (usually 6 months), combination therapy to prevent resistance and kill growing/resting organisms

Question 260

What are the main points from history/examination which would suggest chronic pancreatitis in a patient with acute diarrhoea?

Answer 260

Often results from previous epidsodes of acute pancreatitis Alcohol history important

Question 261

When are carbapenems used?

Answer 261

When worried about resistance - lots of antibiotic related harm

Question 262

Describe the mechanism of action of vancomycin

Answer 262

Inhibits cell wall formation in gram +ve only (no gram -ve action - too big to get through outer membrane) Not dependent on penicillin binding proteins so effective against resistant organisms Resistance in clinical isolates v rare

Question 263

How are bacteria broadly classified?

Answer 263

Gram negative or gram positive - different staining, structure and behaviour

Question 264

Describe the process by which AMR develops

Answer 264

1. Patient acquires infection 2. Antibiotics given to treat infection 3. Infection causing organism wiped out, other organisms affected 4. Resistant organisms emerge and overgrow 5. Resistant organisms transferred via skin/stool to environment

Question 265

Give examples of new infectious diseases which have appeared in recent times

Answer 265

HIV, Ebola, Zika virus, Candida auris, Middle Eastern Respiratory Syndrome

Question 266

How long is the incubation period in Dengue fever?

Answer 266

Incubation 5-14 days

Question 267

Describe the clinical features of malaria

Answer 267

* Clinical features * Fever, malaise, headache, myalgia, diarrhoea etc. (often flu-like symptoms) * Anaemia * Jaundice * Renal impairment * Severe malaria * Parasitaemia \>2% (percentage of red cells with parasites) * Cerebral malaria * Severe anaemia * Renal failure * Shock * DIC * Acidosis * Pulmonary oedema

Question 268

What are the main points from history/examination which would suggest ischaemic bowel in a patient with acute diarrhoea?

Answer 268

Often older patients with a history of vascular disease or atrial fibrillation Presents with diarrhoea, abdominal pain is prominent symptom

Question 269

Which bacteria are sensitive/resistant to clarithromycin?

Answer 269

Highly sensitive - streptococcus, staphylococcus Senstivie - neisseria, haemophilus Minimally sensitive - enterococcus Resistant - clostridium, bacteroides, pseudomonas, E. coli and other coliforms Atypicals also sensitive - legionella, mycoplasma, coxiella, chlamydia, chlamydophila

Question 270

List the regions defined by geosentinel surveillance

Answer 270

Central America Caribbean South America Sub-Saharan Africa Southeast Asia South Central Asia Other developing regions

Question 271

Where are staphylococci bacteria usually found?

Answer 271

Skin and mucous membranes

Question 272

How is guided antibiotic therapy used clinically?

Answer 272

* Use antibiotic which has limited action to the bacteria causing infection (narrow spectrum) * If possible limit penetration to site of infection * Achieve clinical cure with as little impact on colonisation and resistance as possible

Question 273

Which drugs do macrolides interact with?

Answer 273

* Clarithromycin - over 400 drug interactions * Cytochrome P450 inhibitor - causes drug interactions * Simvastatin - if prescribed with clarithromycin simvastatin levels exponentially rise * Avoid co-prescription * Temporarily stop simvastatin * Atorvastatin * Warfarin

Question 274

How is rifampicin usually used?

Answer 274

* As part of combination therapy for Tuberculosis * In addition to another antibiotic in serious gram positive infection (esp. staph aureus)

Question 275

Describe the clinical presentation of viral haemorrhagic fever

Answer 275

1. Exposure 2. Up to 21 days later - non-specific febrile illness 3. Haemorrhagic manifestions 4. Sepsis syndrome/shock (secondary bacterial infection through loss of mucous membranes) 5. Death

Question 276

How can antibiotic resistance be combatted without the use of new antibiotics?

Answer 276

Taking a multidrug approach by combining different antibiotic compounds with each other, or by using a combination of antibiotics with non-antibiotics

Question 277

Describe the mechanism of action of bacteriostatic antibiotics

Answer 277

* Suppresses growth but doesn't directly sterilise infected site * Requires additional factors to clear bacteria - immune mediated killing * Immune system can usually easily mop up the bacteria - only a problem in areas with little immune penetration (e.g. heart valves) or in very immunocompromised individuals

Question 278

How is mycoplasma pneumoniae treated?

Answer 278

* No cell wall, can’t use beta lactams (penicillins/cephalosporins) * Have to use antibiotics which have different targets * Macrolides (clarithromycin) - ribosome * Tetracyclines (doxycycline) - ribosome * Quinolones (ciprofloxacin) - DNA

Question 279

What are ESBLs?

Answer 279

* Extended spectrum beta lactamases - enzymes produced by enterobacteriaceae such as E. coli and Klebsiella (usually found in the gut) which makes them resistant to antibiotics e.g. Penicillins, Cephalosporins, Carbapenems, Fluoroquinolones and Aminoglycosides * Increasing incident of ESBLs globally * E.g. New Dehli metallo-beta-lactamase 1 (NDM-1) producing enterobacteriaceae * Spread from Asia to UK via air travel

Question 280

Which bacteria are sensitive/resistant to meropenem?

Answer 280

Highly sensitive - staphylococcus (not MRSA), E. coli, other coliforms, neisseria, haemophilus, pseudomonas, bacteroides, clostridium, streptococcus Sensitive - enterococcus

Question 281

Describe the types of haemophilus influenzae

Answer 281

1. Typeable - B (vaccinated against) 2. Non-typeable * Colonisation of upper respiratory tract - can cause ENT infections, conjunctivitis, sinusitis, pneumonia * Abrupt onset * Cough * Fever * Pleuritic chest pain * Dull percussion * Coarse crepitations * Increased vocal resonance

Question 282

Describe the pathogenesis of infective endocarditis

Answer 282

* Infective endocarditis = infection of the endocardial surface of the heart valves * Can involve previously normal valves, a valve damaged as a result of prior endocarditis, rheumatic heart disease or a degenerative process or a prosthetic valve * Fibrin and platelets attach to the surface of damaged heart valves producing a sterile thrombotic endocarditis * Certain bacteria can adhere to these lesions on the valvular surface and initiate an inflammatory response that leads to further fibrin deposition, thus leading to maturation of the lesions - these masses of fibrin and bacteria = vegetations

Question 283

What combination can be used which includes trimethoprim?

Answer 283

Co-trimoxazole: * Combination antibiotic with sulphamethoxazole * Significant additional toxicity * Bone marrow suppression * Stevens Johnson syndrome * Relatively few advantages * Used in certain uncommon infections by specialists * Pneumocystitis jjrovecii pneumonia (usually occurs in HIV)

Question 284

Explain AMR and one health

Answer 284

* Dissemination of antibiotics and antibiotic resistance occurs within agriculture, community, hospital, waste water treatment and associated environments * Interconnection between human healthcare, animals, agriculture etc.

Question 285

How does traveller's diarrhoea typically clinically present?

Answer 285

* Often day 4-14 travel * Self limiting * 1 to 5 days * 8 to 15% last \>1 week * Symptoms (ETEC) * Anorexia, malaise and abdominal cramps * Watery diarrhoea (no blood) * Fever nausea and vomiting * Unusual symptoms in travellers diarrhoea - tenesmus, rushing to toilet, blood in stool, lots of pain * More likely to indicate salmonella/shigella etc.

Question 286

Should a patient with suspected endocarditis be started on antibiotic therapy?

Answer 286

* Depends on clinical assessment of how acutely ill the patient is - if not acutely unwell antibiotics are not indicated * Starting antibiotics too early will sterilise all future blood cultures - will need to treat empirically without positive cultures * Usually best to wait and identify a causative organism before starting antibiotic treatment * Make sure patient is monitored in case condition deteriorates

Question 287

How is a rapidly progressing/immediately life-threatening infection dealt with in primary care?

Answer 287

Rapid admission to hospital, consider pre-hospital Rx

Question 288

How does the number of reported penicillin allergies vary from the actual number of people with a penicillin allergy?

Answer 288

* Reported allergy to beta-lactams very common - around 1:10 patients report penicillin allergy * Often reported hypersensitivity syndrome is non-allergic * GI symptoms * Therapeutic failure * Often reason for reported allergy is unclear

Question 289

When did ESBLs first emerge?

Answer 289

* ESBL called CTX-M detected in early 1990s * Appeared simultaneously in Europe (Germany) and South America (Argentina) * CTX-M - cefotaximase-Munich * 4 month Munich child with Otitis media 1990

Question 290

Describe the development of C diff infection

Answer 290

* Antibiotics cause reduced gut microbial species and diversity * Ingestion of C. diff spores from the environment - can be difficult to eradicate from hospitals * C diff spores germinate - dysbiosis of the gut microbiome * Development of C diff infection - severe diarrhoea, abdominal pain, nausea and fever, inflammation and cell death (can progress to pseudomembraneous collitis) * Has developed resistance to common antibiotic classes

Question 291

Describe the pathogenesis of septic arthritis

Answer 291

* Develops as a result of haematogenous seeding or direct inoculation of bacteria into the joint * Most commonly via haematogenous seeding, the synovial membrane has no limiting basement membrane, allowing organisms to enter the joint space * Most commonly causes by organisms able to adhere to the synovial tissue e.g. staphylococcus aureus * Direct inoculation via trauma, arthroscopy or other surgery, intra-articular injection

Question 292

List the features of a systemic inflammatory response

Answer 292

* 2 or more of * Heart rate \>90bpm * Temp \>38 or \>36 * Respiratory rate \>20 per minute * WCC \>12 or \<4

Question 293

Which antibiotics are associated with causing the majority of C diff infections?

Answer 293

4Cs: * Clindamycin * Co-amoxiclav * Cephalosporins * Ciprofloxacin All antibiotics can cause C diff - even those that treat it

Question 294

What are the main points from history/examination which would suggest inflammatory bowel disease in a patient with acute diarrhoea?

Answer 294

Often younger patient with bloody diarrhoea Will often give a history of an irritable bowel, may have weight loss

Question 295

What investigation is important in MRSA bacteraemia?

Answer 295

Risk of endocarditis - need echo and ECG ECG - assess the PR interval, may be prolonged if valvular abscess present

Question 296

List the clinical features of Dengue fever

Answer 296

* 'Breakbone' fever * Headache * Fever * Retro-orbital pain * Arthralgia/myalgia * Rash - sunburn-like * Cough * Sore throat * Nausea * Diarrhoea * Laboratory * Leucopenia * Thrombocytopenia * Transaminitis

Question 297

Define minimum inhibitory concentration

Answer 297

* Minimum dose of antibiotic required to inhibit growth of bacteria * E-strip with low to high concentration of antibiotics * Solution of bacteria onto agar plate - growth where not inhibited by antibiotics * Number on scale = MIC

Question 298

How long should antibiotics be prescribed for in lower UTIs?

Answer 298

* Females - 3 days * Males - 7 days

Question 299

List the important beta-lactam antibiotics

Answer 299

* Penicillins e.g. * Benzylpenicillin * Flucloxacillin * Amoxicillin * Cephalosporins e.g. * Ceftriaxone * Carbapenems e.g. * Meropenem * Monobactams - Aztreonam

Question 300

Describe the treatment of an uncomplicated UTI

Answer 300

* Treatment only needs to sterilise urine - no need for systemic activity * Low risk infection so can often wait for culture results * Antibiotics - trimethoprim or nitrofuratoin * Trimethoprim * Currently 1st line for most causes * Avoid in 1st trimester of pregnancy - weak anti-folate action * Penetrates well into prostate so good for men * Lots of resistance * Nitrofuratoin * Excellent broad spectrum of activity * Concentrated in urine so no effect on other tissues * Failure to concentrate in urine in renal failure - avoid * Relatively non-toxic in short courses * Pulmonary fibrosis with long term use * Used in pregnant women

Question 301

Describe the treatment of haemophilus influenzae

Answer 301

* Amoxicillin * Risk of beta lactamase - 1 in 3 have penicillin resistance * Co-amoxiclav * Macrolides (clarithromycin) * Tetracyclines (doxycycline)

Question 302

What is the first line treatment of an uncomplicated UTI?

Answer 302

* Trimethoprim * Not amoxicillin - not active in causative organisms * Not ciprofloxacin - too much harm * Not gentamicin - too toxic, must be given IV (not useful in primary care)

Question 303

What factors contribute to the spread of infection?

Answer 303

* Infectious agent * Reservoirs * Portal of exit * Means of transmission * Portal of entry * Susceptible host

Question 304

How can the likelihood of a positive blood culture result being a contaminant be determined?

Answer 304

* Contaminants picked up from skin, more likely if there was inadequate skin preparation before taking the culture * Coagulase-negative staphylococci are the most common contaminant, not significant in the absence of any long lines e.g. venous pressure line or prosthetic devices e.g. heart valves - good at attaching themselves to foreign bodies and causing infection * Contaminants usually found in one bottle of a blood culture pair - if all 3 sets of blood cultures are positive the culture is highly likely to be significant

Question 305

How are viral haemorrhagic fevers treated?

Answer 305

* Supportive * Corrective coagulopathy/anaemia * Ribavirin - anti-viral

Question 306

Describe the typical clinical presentation of mycoplasma pneumoniae

Answer 306

* Can be non-specific (atypical) * Myalgia, arthralgia - presents with flu-like symptoms * On examination/CXR find consolidation * Can get more generalised manifestations (not just respiratory) * Haemolysis (cold agglutinins) * Guillain-Barre * Erythema multiforme * Cardiac - conduction problems e.g. heart block * Arthritis

Question 307

What are the sources of ESBL resistance?

Answer 307

* Environmental Kluyvera spp. * Spread of resistance genes into E. Coli, klebsiella and enterobacter * Spread to/from - household members and pets, animals and via food/travel * Risk of spread when travelling dependent on travel destination, length of stay, visiting friends and relatives and type of food (ice cream and pastries)

Question 308

Give an example of gram negative cocci and describe their apearance

Answer 308

Neisseria species - kidney bean shaped

Question 309

Describe the typical dosing schedule of gentamicin

Answer 309

* Once daily dosing * Give high initial dose to take advantage of rapid killing * Leave long dosing interval (24-48hrs) to minimise toxicity - less opportunity to accumulate * Measure trough level to ensure drug not accumulating * Give for 3 days only

Question 310

Describe the action and toxicity of tetracyclines

Answer 310

* Similar spectrum of activity to macrolides * Also active against atypical organisms * Relatively non-toxic * Avoid in children and pregnant women * Bone abnormalities * Tooth discolouration

Question 311

Describe the toxicity of trimethoprim

Answer 311

* Usually more toxic in more co-morbid patients * Elevation of serum creatinine * Does not reflect fall in GFR * Related to action on proximal tubules * Elevation of serum K+ * Problematic in patients which chronic renal impairment * Rash and GI disturbance relatively uncommon

Question 312

What are the consequences of malaria infection?

Answer 312

* Red blood cells aggregate, microcirculation clogged * Renal failure, lactic acidosis (hypoxia), cerebral malaria, pulmonary oedema * Don't become unwell until red cells are parasitised

Question 313

Give examples of antibiotics which act by inhibiting folate synthesis

Answer 313

Trimethoprim Metronidazole

Question 314

What would be the appropriate initial treatment for suspected cellulitis?

Answer 314

* Antibiotics - IV flucloxacillin and benzylpenicillin * Analgesia - NSAIDs have been associated with necrotising fasciitis and should be witheld, co-codamol is appropriate * Area of erythema should be marked and closely monitored overnight

Question 315

How is empirical antibiotic therapy used clinically?

Answer 315

* Use antibiotic which has extensive action against any bacteria which might be causing infection (broad spectrum) * Need to penetrate broadly throughout body * Accept that impact on colonisation and resistance may be greater

Question 316

What property allows bacteria to evolve quickly to changing environments?

Answer 316

Very short generation times - 20-30 minutes

Question 317

Why are ESBLs a problem?

Answer 317

Resistant to most antibiotics - few left able to treat them

Question 318

List the risk factors for bacterial pneumonia

Answer 318

Alcoholism Smoking - destroys host defence Immunosuppression e.g. cancer, HIV Airways disease - asthma, COPD Flu infection

Question 319

What is the classical presentation of streptococcus pneumoniae?

Answer 319

* Abrupt onset * Cough * Fever * Pleuritic chest pain (inflamed lung rubbing on pleura) * Dull percussion * Coarse crepitations * Increased vocal resonance * Basal consolidation on X-ray

Question 320

What are beta-lactamases?

Answer 320

* Enzymes that lyse and inactivate beta-lactam drugs * Commonly secreted by gram -ves and S. aureus * Confer high level resistance to antibiotic - total antibiotic failure likely to result

Question 321

In what environment is exposure to viral haemorrhagic illness most likely?

Answer 321

Rural \> urban

Question 322

Which infections is ceftriaxone usually used to treat?

Answer 322

CNS infections caused by strep, neisseria and haemophilus bacteria

Question 323

Which antibiotics are not considered safe in pregnancy?

Answer 323

* Tetracyclines - bone/tooth abnormalities * Trimethoprim - neural tube defects (1st trimester) * Nitrofurantoin - haemolytic anaemia (3rd trimester) * Aminoglycosides - ototoxicity (2nd/3rd trimester) * Quinolones - bone/joint abnormalities

Question 324

How is legionella pneumophila diagnosed?

Answer 324

Culture Serology Urinary antigen test

Question 325

Why is antimicrobial resistance so challenging to overcome?

Answer 325

* AMR is ancient \>30,000 years old * Microbiome * 100 trillion microbes * 10 xs number of human cells * Infinite opportunities for AMR

Question 326

What surgical management should be used in acute cholecystitis?

Answer 326

ECRP - endoscopic retrograde cholangio-pancreatography

Question 327

Describe the pharmacology of beta-lactams

Answer 327

* Most are poorly absorbed from the GI tract - must be given IV * Amoxicillin, flucloxacillin are effective orally - vomiting limits dose * Usually excreted unchanged in urine, some also via bile * Half life varies * Benzylpenicillin = 1 hour * Ceftriaxone = 8 hours * Usually effectively distributed to sites of infection - can penetrate joints, meninges etc.

Question 328

Describe the reservoir of and illness caused by salmonella sp.

Answer 328

Poultry Loose stool and nausea, colic

Question 329

When is metronidazole commonly used?

Answer 329

Often added to therapy in intra-abdominal infections, esp abscess

Question 330

List parasitic causes of traveller's diarrhoea

Answer 330

Giardia Cryptosporidium Cyclospora Microsporidia Isospora Entamoeba histolytica

Question 331

Which bacteria are sensitive/resistant to clindamycin?

Answer 331

Highly sensitive - bacteroides, clostridium, streptococcus, staphylococcus Resistant - enterococcus, E. coli and other coliforms, neisseria, haemophilus, pseudomonas

Question 332

What should be included in a history from a patient with suspected pneumonia?

Answer 332

* Symptoms: * Fever * Cough/sputum * Chest pain * Insidious/abrupt onset * Non-respiratory symptoms * Past medical history * Underlying lung disease * Immunosuppression * Epidemiology * Ill contacts * Travel * Water exposure

Question 333

How long should antibiotics be prescribed for in bacterial meningitis and what is this determined by?

Answer 333

7-21 days, determined by the causative organism

Question 334

What is the likely source of bacteraemia in acute cholecystitis?

Answer 334

Intra-abdominal/biliary source

Question 335

Give examples of infectious agents and their portals of exit

Answer 335

* TB - respiratory tract * Salmonella - faeces * Norovirus - vomit * Blood borne viruses - cuts and injuries * Enterovirus - conjunctival secretions

Question 336

Describe the toxicity of vancomysin

Answer 336

* Nephrotoxicity - more likely with higer doses * Red-man syndrome if injected too rapidly - anaphylactoid reaction, very rare now infusion rates slow * Ototoxicity - rare * Therapeutic drug monitoring undertaken - narrow therapeutic range, aim higher in severe illness

Question 337

Describe the type IV hypersensitivity reaction which can occur in response to beta-lactams

Answer 337

Stephen Johnson's syndrome - widespread rash, mucosal ulceration of mouth and genitals

Question 338

What are the most common illnesses in returning travellers?

Answer 338

* 34% diarrhoea * 23% non-specific fever * 19.5% dermatological - mostly sunburn, some parasites * Respiratory - mostly influenza * Neurologic - encephalopathy * GU, STI

Question 339

Which bacteria are sensitive/resistant to aztreonam?

Answer 339

Highly sensitive - E. coli, neisseria, haemophilus, pseudomonas Sensitive - other coliforms Resistant - staphylococcus, enterococcus, streptococcus, clostridium, bacteroides No gram +ve activity

Question 340

How is a positive blood culture result be interpreted and acted on?

Answer 340

There are three questions to consider when you get a positive blood culture result: 1. Is the isolate a contaminant from skin? 2. If it is not a contaminant, what is the source of the bacteraemia? 3. What antibiotic(s) would be most appropriate according to the source?

Question 341

In what common situations should an antibiotic not be prescribed?

Answer 341

* Community \> hospital * Viral + self-limiting bacteria respiratory tract infections * Otitis media, sinusitis, lower respiratory tract infections, COPD, upper respiratory tract infections, diarrhoea * Evidence shows antibiotic no better than placebo in LRTI in primary care * Asymptomatic bacteruria, uncomplicated cystitis * In-growing toe nails * Leg ulcers without cellulitis * Varicose eczema (mistaken for cellulitis) * Systemic inflammatory response due to cancer, ischaemia, inflammation

Question 342

Give an example of intrinsic resistance of a bacteria

Answer 342

Vancomycin is inactive against Gram negative bacteria (cell wall structure not suitable target)

Question 343

What are the modern uses of chloramphenicol?

Answer 343

* Topical therapy for eyes e.g. bacterial conjunctivitis * Bacterial meningitis with beta-lactam allergy

Question 344

Where are streptococci species normally found?

Answer 344

Usually found on the skin or in the respiratory tract

Question 345

Describe methods of malaria prevention

Answer 345

1. Bite prevention 2. Chemoprophylaxis * Mefloquine * Once weekly - good if long treatment/in children * Psychiatric side effects - vivid dreams --\> psychosis/severe anxiety * Doxycycline * Antibiotic * Daily * Photosensitisation - sunburn * Thrush, dyspepsia * Malarone * Minimal side effects - GI upset, mouth ulcers * Much more expensive - £28/week

Question 346

How is the clinical severity of pneumonia determined?

Answer 346

Severe pneumonia = * CURB65 Score \>2 - C - confusion U - urea \>7 R - respiratory rate \>30 B - BP, diastolic \<60 or systolic \<90 65 - age over 65 years OR * Multilobar consolidation on CXR and/or hypoxia on room air Sepsis - qSOFA * Systolic BP \<100mmHg * Altered mental status * Respiratory rate \>22 breaths/min

Question 347

What antibiotics would be used to treat an MRSA wound infection?

Answer 347

IV vancomycin +/- oral rifampicin, fusidic acid, doxycycline or trimethoprim or oral linezolid or IV daptomycin or IV tigecycline

Question 348

What is usually the first observation to decompensate when a patient is severely ill?

Answer 348

Respiratory rate usually decompensates first In young healthy patients heart rate and BP are usually maintained until they are very unwell

Question 349

Define broad spectrum antibiotics and give an example

Answer 349

* Antibiotics that are active against a wide range of bacteria * Treat most causes of infection but also have a substantial effect on colonising bacteria * E.g. Meropenem * Active against almost all gram positive and negative species * Resistance is rare except for MRSA

Question 350

Define narrow spectrum antibiotics and given an example

Answer 350

* Antibiotics that are active against a limited range of bacteria * Useful only where the cause of the infection is well defined * Have a much more limited effect on colonising bacteria * E.g. Benzylpenicillin * Highly active against streptococci * Most other disease causing bacteria are resistant

Question 351

How many deaths globally are attributable to infectious diseases?

Answer 351

20% - 10 million deaths/year