Lec 14- Antimicrobial therapy

Question 1

Definition

Answer 1

• An infection anywhere in the urinary tract.
• Term UTI refers to anything from asymptomatic bacteriuria to severe pyelonephritis.
• Maybe uncomplicated
  
  • Structurally and functionally healthy urinary tract
• May be complicated
  
  • Abnormal structurally (e.g. obstruction), functionally (e.g. incomplete bladder emptying) or neurologically, prosthetic material in situ
• All UTIs in men, pregnant women and children considered complicated

Question 2

Signs and symptoms

Upper UTI

Answer 2

• Rich blood supply meaning bacteria can enter bloo= sepsis
• Upper UTI (pyelonephritis)
  
  • Systemically unwell
  • Fever +/‐rigors
  • Loin pain and tenderness
  • Nausea/vomiting
  • Hypotension or shock–+/‐symptoms of a lower UTI

Question 3

Signs and symptoms

Lower UTI

Answer 3

• Dysuria
• Frequency
• Suprapubic pain
• Malodorous urine
• Haematuria

Question 4

Aetiology

Answer 4

• Infection may be polymicrobial- culture report shows mixed growth
• Fungal infections, e.g. Candida Albicans
• In pts with an indwelling catheter and abx therapy

Question 5

hggyDiagnosis

Answer 5

• If severe or ≥ 3 symptoms
  
  • TREAT
• If mild or ≤ 2 symptoms:
  
  • Urine dipstick analysis
    
    • Suggestive of bacterial infection:
      
      • Urine cloudy
      • Positive for nitrites and leukocyte esterase–TREAT
• Send culture if:
  
  • Pregnancy- potential damage to a fetus
  • Suspected pyelonephritis
  • Men
  • Failed treatment or persistent symptoms
  • Recurrent UTI, GU tract abnormalities, renal impairment

Question 6

Diagnosis- Don’t treatment

Answer 6

• Don’t treat:
  
  • Asymptomatic bacteriuria in the elderly (v. common).
  • Asymptomatic bacteriuria in those with indwelling urinary catheters.
• Treatment does not reduce mortality or prevent symptomatic episodes. It may, however, expose the patient to side effects and promote antibiotic resistance

Question 7

Lower Urinary Tract infection

Management

Answer 7

• Hydration
• Empiric antibiotic therapy
  
  • Uncomplicated infection
  • 1stline nitrofurantoin (low resistance rates)
  • Alternative agents are trimethoprim or cefalexin
  • Duration of treatment 3 days for uncomplicated infection in women, 7 days for men/ pregnant women

Question 8

Pharmacist interventions for uncomplicated UTI

Answer 8

• Promote hydration
• Analgesia –paracetamol or ibuprofen
• Promote regular review of prophylactic antibiotics to prevent UTI
• Ensure the appropriate duration of treatment for women vs men, pregnant women
• Supply using PGD in community pharmacy becoming more common

Question 9

Acute pyelonephritis

Answer 9

Question 10

Acute Pyelonephritis

Management

Answer 10

• Rehydration, analgesia, renal tract imaging
• Empiric antibiotic therapy
• broad-spectrum to cover a wider range of organisms and potential sepsis
• Need IV initially to ensure good blood levels
• Can rapidly lead to sepsis, AKI- are other medicines still appropriate
• Duration of treatment much longer (7‐14 days)

Question 11

Pharmacist’s role in pyelonephritis management

Answer 11

• Empiric antibiotic review –check culture results, previously known organisms•Check if urine samples sent
• Check if a renal ultrasound or other imaging arranged
• Analgesia, fluids
• Review concurrent medication if AKI
• Promote IV to oral switch or OPAT
• Ensure the appropriate duration of antibiotics

Question 12

Pneumonia

Answer 12

• Defined as an acute infection of the lung tissues with symptoms of acute illness
• Can be seen on CXR as an area of consolidation
• Accounts for 6.6% of deaths worldwide, leading cause of mortality in children worldwide, the mortality rate has not decreased in recent decades
• Mucus etc- clogs, prevent gas exchange= hypoxia,
  
  • Mucus good environment for bacteria to multiply

Question 13

Main symptoms of pneumonia

Answer 13

• It can take around 6 months to fully recover
• If they are better (but not perfect) after 2 weeks then they are not to come back and get more antibiotics

Question 14

Types of pneumonia

Answer 14

• Community acquired-affects between 5‐11 per 1000 adult population; always cover Streptococcus pneumonia
• Hospital-acquired–shift to more Gram‐negative organisms due to selection pressure, e.g. Escherichia coli
• ‘Atypical’–essentially community, caused by organisms which lack a cell wall, e.g. Mycoplasma, Chlamydia
• Aspiration–inhalation of food/stomach contents; suspect with stroke/loss of consciousness- stomach acid damage oesophagus= secondary infections
• Ventilator-associated–affects ITU patients who are intubated, often multi‐resistant organisms

Question 15

Community-acquired pneumonia

Answer 15

• Is usually differentiated into mild, moderate and high severity
• Mortality ranges from <1% for mild, 5‐14% for hospitalised patients, to >30% for high severity admitted to ICU
• Caused by a range of pathogens, most commonly S. pneumonia, Haemophilus influenza, Moraxella catarrhalis

Question 16

Atypical pathogens

Answer 16

• Intracellular pathogens lack a cell wall- must target another way
  
  • Mycoplasma pneumonia, Chlamydia pneumonia, Legionella pneumophila
• More common in younger adults than older
• Can be associated with epidemics/outbreaks
• Cannot be cultured, use urinary antigen or serology to identify
• Treated with macrolides or quinolones- (these don’t target cell wall)

Question 17

Assessing severity

Answer 17

• NICE pneumonia guidelines (2014) recommend CURB‐65 criteria:
  
  • C= new onset confusion
  • U= Urea >7 mmol/L
  • R= Respiratory rate >30 breaths/min
  • B= Blood pressure; systolic <90 mmHgdiastolic <60 mmHg65=
  • Age >65 years old
• In primary care, can use CRB‐65 score

Question 18

Severity

Answer 18

• A score of 0‐1 (risk of death <3%): use oral antibiotics, don’t require hospital admission, amoxicillinmonotherapy
• Score = 2 (risk of death 9%): hospital admission, IV antibiotics if unable to take oral amoxicillin plus clarithromycin
• Score >3 (risk of death 15‐40%): hospital admission, consider ICU review, IV antibiotics mandatorybenzylpenicillin*plus clarithromycin

Question 19

Sepsis

Answer 19

• Ranks in the top 10 causes of death
  
  • The mortality rate is 30% (x 5 higher than stroke)
  • 150,000 hospital admissions each year in the UK
  • Claims 44,000 lives annually in the UK
• Affects allages
• Occurs in:
  
  • The community
  • Long term care facilities
  • Patients admitted to hospital under any and every medical speciality

Question 20

Sepsis- What is it

Answer 20

• Sepsis is characterised by a dysregulated host response to infection mediated by the immune system resulting in organ dysfunction and potentially multi‐organ failure, shock and death

Question 21

The sepsis cascade

Answer 21

• Infection (e.g. chest infection, urinary tract infection)=>
• Release of sepsis initiators –endotoxins and exotoxins from bacteria, e.g. lipopolysaccharide, TSST =>
• Release of endogenous mediators (e.g. TNFα, interleukins, nitric oxide, tissue factor) –activates coagulation mechanisms, complement system, causes endothelial damage=>
• Profound physiological effects (hypotension, tissue hypoperfusion, DIC, lactic acidosis) =>
• Organ dysfunction and septic shock

Answer 22

Question 23

Septic Shock

Answer 23

• Sepsis with hypotension (SBP <90 mmHg) refractory to adequate volume resuscitation (boluses of up to 30 ml/kg of crystalloid fluids)
• Increased lactate >4 mmol/l (a strong predictor of mortality)

Question 24

Red flag Sepsis

Answer 24

Question 25

Treatment of sepsis

Answer 25

• Within the 1sthour:
• The Sepsis Six treatment pathway:
  
  • Start high flow oxygen
  • Take blood cultures
  • Give IV antibiotics
  • Give IV fluid resuscitation
  • Measure lactate
  • Measure hourly urine output

Question 26

Sepsis- Antibiotics

Answer 26

• Usually need broad-spectrum cover, until causative agent known
  
  • E.g. amoxicillin, gentamicin and metronidazole
  • E.g. piperacillin/tazobactam or meropenem
• If the source is clear, acceptable to be more focused, e.g. high severity CAP regimen for chest source
• Therapy should be narrowed down once source identified /organism isolated
• Cultures before antibiotics if possible, but antibiotics should not be delayed to get cultures

Question 27

Other Therapeutic Interventions‐ Treatment is complex and may include:

Answer 27

• Fluid therapy
• Vasopressors
• Inotropes
• Blood products
• Mechanical ventilation (ITU)•Surgery –e.g. incision and drainage, debridement
• Sedation (ITU)
• Analgesia
• Renal replacement (ITU)
• Stress ulcer prophylaxis (ITU)
• Imaging