IC1 & 3 Flashcards
Possible cause of superinfection
Antibiotic disrupts normal microbiota, causing bad bacteria to invade tissues
Systematic approach to using and monitoring antimicrobial therapy in patients
- Confirm presence of infection
- Identification of pathogen
- Selection of antimicrobial and regimen
- Monitor response
Identify subjective evidence that indicate the presence of an infection.
Localised symptoms
• Diarrhoea, nausea, vomiting, abdominal distension
• Cough, purulent sputum
• Dysuria, frequency, urgency
*Dysuria - pain or a burning sensation when you pee
• Pain and inflammation at site of infection – erythema, swelling, warmth
• Purulent discharge (wound, vaginal, urethral)
Systemic symptoms
• Feverish, chills, rigors
• Malaise
• Palpitations
• Shortness of breath
• Mental status changes
• Weakness
Identify objective evidence that indicate the presence of an infection.
- Vital signs
- Lab tests
- Radiological imaging
Differences between prophylactic, empiric and culture-directed (aka definitive) antimicrobial therapy
- Prophylactic: Antibiotics given to prevent an infection
- Empiric: Microbiological result not avail; Antibiotic use is based on clinical presentation of likely site of
infection, likely organism causing infection at that site and likely
susceptibility (from antibiogram) - Antibiotics choice is based on patient specific microbiological (ie
culture and susceptibility) results
Host factors that affect the selection of antimicrobial agent to treat infection.
• Age
• G6PD deficiency
• History of allergy and ADR
• Pregnancy or lactation
• Renal or hepatic impairment
• Status of host immune function
• Severity of illness
• Recent antimicrobial use
• Healthcare-associated risk factors
Organism factors that affect the selection of antimicrobial agent to treat infection.
- Identity of the infecting organism
- Susceptibility/Resistance of the infecting organism
Drug factors that affect the selection of antimicrobial agent to treat infection.
• Active against suspected organism
• Ability to reach the site of infection
• Pharmacokinetics-Pharmacodynamics (PK-PD) characteristics
• Route of administration
• Side effect profiles
• Drug interactions
• Cost
Advantages for using combination antimicrobial therapy
Extend spectrum of activity, Achieve synergistic bactericidal effect & Prevent development of resistance
Possible reasons for an unsatisfactory response to antimicrobial therapy
• Inappropriate diagnosis
• Inappropriate choice of agent
• Subtherapeutic concentration
• Collections or abscess – needs surgery or drainage
• Impaired host defense
• Superinfection
• Toxicity of the drug
Alternative causes of high procalcitonin apart from bacterial infection
ESRF/ traumatic brain injury
Vital signs that indicate presence of an infection
- Fever (more than or equal to 38)
- Hypotension (SBP < 120)
- Tachypnea (RR > 22 bpm)
- HR > 90 bpm
- Mental status esp in elderly
Lab tests that indicate presence of an infection
- Elevated/ depressed total white (normal: 4-10 x 10^9 / L)
• Increased neutrophils (normal range 45-75%) *Look at baseline
• Increased C-reactive protein (CRP) (normal <10 mg/L, infection > 40
mg/L)
• Increased erythrocyte sedimentation rate (ESR) (more utility for bone and joint infection)
• Increased procalcitonin (more specific than CRP)
Radiological imaging that indicate presence of an infection
• Look for tissue changes, collections, abscess, obstructions
• X-ray (chest, bone)
• Ultrasound
• Computerized tomography (CT) scan
• Magnetic resonance imaging (MRI)
Why are follow-up culture are much less reliable than pretreatment cultures?
• may result in false negative results
• subsequent cultures may not reflect the initial causative organisms
Do colonisers elicit host response?
No
likely coloniser from urine culture
yeast
likely contaminant from blood culture
Staphylococcus epidermidis (Coagulase negative staphylococcus), bacillus spp.
Empirical tx for ventilator associated pneumonia
piperacillin-tazobactam + ciprofloxacin to cover Pseudomonas aeruginosa
therapy of polymicrobial infections e.g. hospital-acquired pneumonia
piperacillin-tazobactam + vancomycin
Disadvantages for using combination antimicrobial therapy
• Increased risk of toxicity and allergic reactions
• Increased risk of drug interactions
• Increased cost
• Selection of multi-drug resistant bacteria
• Increased risk of superinfections (fungal infections, CDAD)
• Concern for antagonistic effect (?)
Antibiotics generally safe in pregnancy and lactation
Beta lactams, macrolides
Antibiotics generally cautioned/ avoided in pregnancy
Co-trimoxazole, fluoroquinolones & tetracyclines
Antibiotics NOT used to treat CNS (cannot reach adequate levels)
1st and 2nd gen cephalosporins, AGs, macrolides & clindamycin
drug of choice for prostatitis
Ciprofloxacin and co-trimoxazole: distribute well to the prostate
Bactericidal antibiotics
• Beta-lactams
• Glycopeptides
• Aminoglycosides
• Fluoroquinolones
Bacteriostatic antibiotics
• Macrolides
• Tetracyclines
• Trimethoprim and sulfonamides
What is post-antibiotic effect?
ability of an antimicrobial agent to persistently suppress bacterial growth even at low or undetectable concentration.
Concentration-dependent antibiotic
AGs/ fluoroquinolones
Time-dependent antibiotic
Beta lactams
Dosing strategy for Concentration-dependent bacterial killing
• Optimize Peak:MIC ratio (peak is 8-10x above MIC)
• Usually means larger doses at extended intervals
Dosing strategy for time-dependent bacterial killing with no persistent effect (short half life)
• Optimize %T > MIC (40-70% of dosing interval above MIC)
• More frequent dosage administration
• Continuous IV infusion or prolonged intermittent infusion
• Block excretion (probenecid)
Dosing strategy for time-dependent bacterial killing with persistent effect (long half-live or post-antibiotic effect)
• Optimize AUC:MIC ratio (e.g. for vancomycin - target of AUC24-h /MIC = 400-600 for MRSA)
• Dependent on total daily dose
PK-PD measurement for time-dependent / moderate-long persistent effect
24-h AUC:MIC
PK-PD measurement for time-dependent / no persistent effect
%T>MIC
PK-PD measurement for Concentration- dependent / Prolonged persistent effect
- Cmax:MIC (more useful)
- 24-h AUC:MIC
Duration of use for UTI/ Resp/ Skin infection
5-14 days
