Antibiotic choices in sepsis Flashcards
What are the key antibiotic patterns/principles for empiric sepsis treatment?
- Core principle: Match antibiotic coverage to likely pathogens based on source
Pattern-based approach: - Most regimens include gram-negative coverage (aminoglycoside or broad-spectrum β-lactam)
Add gram-positive coverage based on risk factors (especially MRSA risks)
Add anaerobic coverage for GI, gynecological, diabetic foot infections
Add atypical coverage for respiratory infections (macrolide)
Add specific coverage based on special circumstances (water exposure, melioidosis risk) - Severity-based escalation: More severe sepsis = broader coverage
What are the core antibiotic “building blocks” used across multiple organ systems?
Gram-negative coverage options:
Aminoglycosides (Tobramycin/Gentamicin): Used for urinary, intra-abdominal, undifferentiated sepsis
3rd gen cephalosporins (Ceftriaxone): Used for meningitis, pneumonia, undifferentiated sepsis
Anti-pseudomonal β-lactams (Piperacillin-Tazobactam): Used for neutropenic fever, necrotizing infections
Carbapenems (Meropenem): Used for resistant organisms, tropical infections, severe sepsis
Gram-positive coverage options:
β-lactams (Flucloxacillin): Primary coverage for MSSA
Vancomycin: Added when MRSA risk factors present
Anaerobic coverage options:
Metronidazole: Added for abdominal, gynecological sources
Clindamycin: Used for toxin suppression in necrotizing infections
Atypical coverage options:
Azithromycin: Added for pneumonia
What are the high-risk criteria for sepsis?
Systolic BP <90mmHg (or drop >40 from normal)
Lactate ≥2mmol/L
Non-blanching rash / Mottled / Ashen / Cyanotic
Respiratory rate ≥25 breaths per min
New oxygen requirement to keep oxygen saturation ≥92%
Heart rate ≥130 beats per min
Has not passed urine in past 18 hours OR urinary output (UO) <0.5mL/kg/hr
Evidence of new or altered mental state
Recent chemotherapy
What are the moderate risk criteria for sepsis?
Systolic BP 90–99mmHg
Respiratory rate 21–24 breaths per min
Heart rate 90–129 beats per min OR new arrhythmia
Has not passed urine in past 12–18 hours
Temperature <35.5°C or ≥38.5°C (≥38.0°C for maternity patients)
Family members / carers concerned about mental state
Acute deterioration in functional ability
Which patients should be screened for sepsis?
Looks sick
You suspect they may have sepsis
Has a suspected infection
Patient / family / carers concerned about patient condition
Current or recent fever with or without chills or rigors
Hypothermia <35.5°C
Signs of clinical deterioration (e.g., change in behavior or new onset confusion or total Q-ADDS / Q-MEWT score of ≥4)
What are the timeframes for commencing actions in sepsis management?
30 minutes: From recognition of neutropenic or meningococcal sepsis
1 hour: From recognition of septic shock
1 hour: From triage or recognition of sepsis where there is high likelihood that organ dysfunction is due to infection
3 hours: From triage or recognition of organ dysfunction where there is less certainty this is due to infection, but concern for infection persists after rapid clinical assessment
What is the pattern for CNS infection (meningitis) antibiotic coverage?
Core regimen: Ceftriaxone 2g IV, 12 hourly + Dexamethasone 10mg IV, 6 hourly
Key additions based on risk factors:
Listeria risk: Add Benzylpenicillin 2.4g IV, 4 hourly
Resistant pneumococci risk: Add Vancomycin 25-30mg/kg
Organisms targeted:
Ceftriaxone → S. pneumoniae, N. meningitidis, H. influenzae
Benzylpenicillin → Listeria monocytogenes
Vancomycin → Resistant pneumococci
Rationale: Requires agents that cross blood-brain barrier with rapid bactericidal action
What is the pattern for respiratory infection (pneumonia) antibiotic coverage?
Core regimen: β-lactam + Macrolide
Dry season: Ceftriaxone 2g IV daily + Azithromycin 500mg IV daily
Wet season (tropical): Meropenem 2g IV, 8 hourly + Azithromycin 500mg IV daily
Key additions based on risk factors:
MRSA risk or severe sepsis: Add Vancomycin 25-30mg/kg
Organisms targeted:
β-lactam → S. pneumoniae, H. influenzae
Macrolide → Atypical pathogens (Mycoplasma, Legionella, Chlamydophila)
Meropenem (wet season) → B. pseudomallei (melioidosis)
Rationale: Combination therapy ensures coverage of both typical and atypical respiratory pathogens
What is the pattern for urinary tract infection antibiotic coverage?
Core regimen: Tobramycin 4-5mg/kg IV ONCE + Ampicillin 2g IV, 6 hourly
Organisms targeted:
Tobramycin → Gram-negative rods (E. coli, Klebsiella, Pseudomonas)
Ampicillin → Enterococci
Rationale:
UTIs primarily caused by gram-negative organisms, with Enterococcus as a consideration
Aminoglycosides concentrate in urine, making them particularly effective
Once-daily dosing optimizes bacterial killing while minimizing nephrotoxicity
What is the pattern for intra-abdominal infection antibiotic coverage?
Core regimen: Tobramycin 4-5mg/kg IV ONCE + Ampicillin 2g IV, 6 hourly + Metronidazole 500mg IV, 12 hourly
Organisms targeted:
Tobramycin → Gram-negative enteric bacteria (E. coli, Klebsiella)
Ampicillin → Enterococci, some Streptococci
Metronidazole → Anaerobes (Bacteroides, Clostridium)
Rationale:
Triple therapy needed for polymicrobial nature of intra-abdominal infections
Must cover gram-negative aerobes, gram-positive cocci, and anaerobes
Can be simplified with single broad-spectrum agents like Piperacillin-Tazobactam in severe sepsis
What is the pattern for skin/soft tissue infection antibiotic coverage?
Core regimen: Flucloxacillin 2g IV, 6 hourly
Key additions based on risk factors:
MRSA risk: Add Vancomycin 25-30mg/kg
Necrotizing infection: Add Clindamycin 600mg IV, 8 hourly
Water exposure: Add Ciprofloxacin 400mg IV, 8 hourly
Organisms targeted:
Flucloxacillin → Staphylococcus aureus (MSSA), Streptococci
Vancomycin → MRSA
Clindamycin → Toxin suppression in severe streptococcal/staphylococcal infections
Ciprofloxacin → Vibrio, Aeromonas (water exposure)
Rationale: Target staphylococcal/streptococcal coverage first, with additions based on specific risk factors
What is the pattern for febrile neutropenia antibiotic coverage?
Core regimen: Piperacillin-Tazobactam 4/0.5g IV, 6 hourly
Key additions based on risk factors:
Severe sepsis/septic shock: Add Tobramycin 7mg/kg IV ONCE
MRSA risk or line infection: Add Vancomycin 25-30mg/kg
Organisms targeted:
Piperacillin-Tazobactam → Broad spectrum including Pseudomonas
Tobramycin → Enhanced gram-negative coverage, especially Pseudomonas
Vancomycin → MRSA, line-associated infections
Rationale:
Requires immediate broad-spectrum coverage before cultures return
High mortality risk necessitates aggressive empiric therapy
Anti-pseudomonal coverage essential due to high risk in neutropenic patients
What is the pattern for undifferentiated sepsis antibiotic coverage?
Dry season: Tobramycin 4-5mg/kg IV ONCE + Flucloxacillin 2g IV, 6 hourly
Wet season tropical: Meropenem 2g IV, 8 hourly
Key additions based on risk factors:
MRSA risk: Add Vancomycin 25-30mg/kg
Toxic shock concern: Add Clindamycin 600mg IV, 8 hourly
Meningococcal concern: Add Ceftriaxone 2g IV, 12 hourly
Organisms targeted:
Targets most common pathogens with regional considerations
Escalates coverage in septic shock
Rationale: Broad empiric coverage until source identified, with tropical considerations during wet season
What are the risk factors for Methicillin-resistant Staphylococcus aureus (MRSA) infection?
Chronic underlying disease (e.g., kidney disease, diabetes)
Immunosuppression
Chronic wounds or dermatitis
Injection drug use
Living in close quarters or communities with high MRSA prevalence
Known colonization with MRSA
What are the risk factors for multidrug-resistant infection?
Recent admission (within 12 months) to an overseas hospital with a high prevalence of multidrug-resistant organisms
Previous colonization or infection with a resistant Multidrug-Resistant Gram-Negative organism (MRGN)
What are the risk factors for Listeria?
Immunosuppression
50 years
History of hazardous alcohol consumption
Pregnancy
Debilitation
What are the risk factors for tropical infection (Burkholderia pseudomallei or Acinetobacter baumannii)?
Travel to tropical countries or north of Mackay
AND at least one of:
Diabetes
Hazardous alcohol consumption
Chronic kidney or lung disease
On immunosuppressants
What are the key properties and dosing considerations for aminoglycosides (Tobramycin/Gentamicin)?
Spectrum: Excellent gram-negative coverage including Pseudomonas
Dosing approach:
Dose according to IBW or ABW (whichever is less)
Where ABW is >20% of IBW, use Adjusted Body Weight
Sepsis WITHOUT shock: 4-5mg/kg (max 500mg)
Sepsis WITH shock: 7mg/kg (max 700mg)
Repeat dosing ≥24 hours after first dose
Administration: Inject over 3-5 min, diluted in 20mL 0.9% NaCl
Key consideration: Cannot be mixed with penicillins/cephalosporins (will inactivate)
What are the key properties and dosing considerations for Vancomycin?
Spectrum: MRSA, coagulase-negative staphylococci, resistant streptococci
Dosing approach:
25-30mg/kg ABW loading dose (max 3000mg)
Dose according to Actual Body Weight
Subsequent doses based on levels
Administration:
Dilute to concentration 2.5-5mg/mL
Infusion times:
1g or less: 60min
2g dose: 120min
3g dose: 180min
Key consideration: Monitor for infusion reactions (“Red Man Syndrome”)
What are the indications for adding Clindamycin in severe sepsis?
Indications:
Necrotizing fasciitis
Toxic shock syndrome
Severe streptococcal infections
Rationale:
Inhibits bacterial protein synthesis and toxin production
Added for its anti-toxin effect even when other antibiotics provide coverage
Continues to work in high-inoculum infections with poor perfusion
Dosing: 600mg IV, 8 hourly
Administration: Infuse 600mg over 20min, diluted in 50mL 0.9% NaCl
What are the key immediate actions in sepsis management?
Measure (or remeasure) lactate
Take 2 sets of blood cultures
Commence or review antibiotics
Commence IV fluids if clinically indicated
Consider vasopressors/inotropes for hypotension
Facilitate source control
Reassess and monitor response to resuscitation
Document and communicate ongoing management
What are the targets for resuscitation in sepsis?
Oxygen saturation ≥92% and titrate to range of 92–96% (88–92% if COPD)
Systolic BP >100mmHg
Urine output >0.5 to 1.0mL/kg/hr
What are the fluid resuscitation guidelines for sepsis?
Consider volume based on patient’s weight, cardiac function, comorbidities, current volume status and hemodynamics
If bolus indicated, rapidly infuse 250–500mL IV or intraosseous Hartmann’s or sodium chloride 0.9%
Consider albumin 5% solution for patients with septic shock
Assess response to fluid and consider repeating bolus if clinically indicated
Do NOT exceed 30mL/kg without senior medical input
If IV access not possible, consider intraosseous route
