CRITICAL CARE - Empiric second line antibiotic guidelines for Level 2 and 3 (Antimicrobial)

TAM (Treatments and Medicines) NHS Highland
NHS Highland

Indication/Antibiotic Recommendation/Comments

Guidelines for Second Line Empiric Treatment of Infections in Level 2 and 3 Critical Care

On admission to level 2 or 3 critical care, complete a full antibiotic history in relation to the active infection.  Ensure adequate source control where possible (ie drainage of collections or abscesses).  Consider other causes of systemic deterioration eg recent surgical intervention, acute on chronic respiratory disease.  Use existing protocols for dosing of vancomycin and gentamicin.  Split doses evenly in 24 hours: x 2 = every 12 hours, x 3 = every 8 hours, x 4 = every 6 hours.

Indication Antibiotic Recommendation
(all doses IV)		 Comments
Sepsis of unknown focus Aztreonam 2 grams every 8 hours (as NHS Tayside), can increase to 6 hourly dosing if required PLUS metronidazole 500mg x 3 PLUS vancomycin (covers MRSA) If strong suspicion of group A Strep or Staph Toxic Shock Syndrome, discuss with microbiology and consider adding clindamycin and using immunoglobulin.
Community acquired pneumonia If antibiotic switch considered necessary: Levofloxacin 500mg x 2
(see BNF warnings and MHRA Drug Safety Alert (updated 22 January 2024))		 If patient has following risk factors treat as HAP: recent hospital admission; recent antibiotic therapy.
Hospital acquired pneumonia Symptoms > 48 hours post admission Aztreonam 2 grams every 8 hours (as NHS Tayside), can increase to 6 hourly dosing if required PLUS vancomycin
Second line: ciprofloxacin 400mg every 8 hours (see BNF warnings and MHRA Drug Safety Alert (updated 22 January 2024)) PLUS vancomycin		  
Severe community-acquired pneumonia where MSSA/MRSA suspected eg recent influenza or IVDU Discuss with microbiologist ADD linezolid 600mg x 2
For treatment of microbiologically proven MSSA pneumonia: levofloxacin 500mg x 2 (see BNF warnings and MHRA Drug Safety Alert (updated 22 January 2024)) PLUS flucloxacillin 2g x 4		 Note: Hypertensive crises have occurred in patients taking MAOIs (linezolid is one) and metaraminol.  The pressor effects of adrenaline, isoprenaline and noradrenaline may be unchanged or moderately increased.
Suspected necrotising staphylococcal lung infection Suspect Panton-Valentine Leukocidin (PVL) toxin producing S. aureus strain: levofloxacin 500mg x 2 (see BNF warnings and MHRA Drug Safety Alert (updated 22 January 2024)) PLUS linezolid 600mg x 2 If deteriorating or severe disease consider IV immunoglobulin.
Aspiration pneumonia
Aspiration often leads to chemical pneumonitis - use antibiotics only treat where infection suspected		 Metronidazole 500mg x 3 PLUS amoxicillin 1g x 3
Penicillin allergy: metronidazole PLUS clarithromycin 500mg x 2
Severe infection or previous antibiotics*: aztreonam 2g x 4 PLUS amoxicillin 1g x 3 PLUS metronidazole 500mg x 3
Severe infection, penicillin allergy: levofloxacin 500mg x 2 (see BNF warnings and MHRA Drug Safety Alert (updated 22 January 2024)) PLUS metronidazole 500mg x 3		 Infection indicated by change in sputum quality to purulent/mucropurulent or fever and new chest X-ray changes.
* Antibiotics in the last 2 weeks increases colonisation of oropharynx and gram negative organisms.
Intra-abdominal sepsis Aztreonam 2g every 8 hours (as NHS Tayside), can increase to 6 hourly dosing if required PLUS amoxicillin 1g x 3 PLUS metronidazole 500mg x 3
Penicillin allergy: aztreonam 2g every 8 hours (as NHS Tayside), can increase to 6 hourly dosing if required PLUS vancomycin PLUS metronidazole 500mg x 3		 Discuss with microbiologist if illness unresponsive or severe illness.
Necrotising fasciitis Meropenem 2g x 3 PLUS clindamycin 1.2g x 4 Seek urgent surgical opinion and consult microbiology (notify Public Health).

Matrix of selected antimicrobial/antibacterial agent combination activity

Combinations

Drug information (fluid restriction, renal dysfunction, obesity)

SELECTED DRUG INFORMATION(taken from IV Administration Guide, Renal Drug Database, SPC etc)

DRUG Usual dose (IV) Renal dosing Administration Fluid restriction Actual or Ideal BW?
Amoxicillin 1 to 2g every 6 hours (up to 2g every 4 hours for listeria) GFR (ml/min): <10: 250mg to 1g every 8 hours, max 6g/day
CVVHD: dialysed, dose as normal
HDF/high flux: dialysed, dose as GFR <10ml/min		 Slow IV injection OR infusion over 20 to 60 mins Slow IV injection ABW - give max dose
Aztreonam 1 gram every 8 hours to 2 grams every 6 hours GFR (ml/min):10 to 20: 1g x 3 <10: 1 to 2g loading then 500mg x 3
CVVHD/HDF: 2g every 12 hours		 Slow IV injection OR infusion over 20 to 60 mins Slow IV injection ABW - give 2g every 6 hours by infusion
Benzyl penicillin 1·2g every 6 hours (up to 2·4g every 4 hours for endocarditis) GFR (ml/min): 10 to 20: 600mg to 2·4g every 6 hours
GFR (ml/min): >10: 600mg to 1·2g every 6 hours
CVVHD: dialysed, dose as GFR 10 to 20ml/min
HDF: dialysed, dose as GFR <10ml/min		 Slow IV injection OR infusion over 20 to 60 mins.  Dose over 1.2g give at 300mg/min Slow IV injection ABW - give max dose
Ciprofloxacin 400mg every 8 hours
(see BNF warnings and MHRA Drug Safety Alert (updated 22 January 2024))		 GFR (ml/min): <10: 50% of normal dose
CVVHD/HDF: dose as normal		 Infusion over 60 mins Pre-made bag* (100ml) ABW - give 800mg x 2 if BMI >40
Clarithromycin 500mg every 12 hours GFR (ml/min): <10 to 30: oral/IV 250mg to 500mg every 12 hours
CVVHD/HDF: unknown dialysis ability, dose as in GFR <10 to 30ml/min		 Infusion over 60 mins Can dilute in 100ml for CVC admin Unknown, max dose 500mg x 3
Clindamycin 1·2g every 6 hours No adjustments required Infusion over 60 mins Max 18mg/ml  
Co-amoxiclav 1·2g every 8 hours GFR (ml/min): <30
CVVHD/HDF: 1·2g x 2		 Slow IV injection OR infusion over 30 to 40 mins Slow IV injection Consider giving same dose by infusion
Co-trimoxazole 960mg every 12 hours
PJP: 120mg/kg/day in 2 to 4 doses
S.maltophilia: 90mg/kg/day in 2 to 4 doses		 GFR (ml/min): 15 to 30: PCP = 60mg/kg 12 hourly for 3 days then 30mg/kg 12 hours.  Other indications = 50% of dose.
GFR (ml/min): <15: PCP = 30mg/kg 12 hourly.  Other indications = 50% of dose.
CVVHD/HDF: dose as in GFR 15 to 30ml/min		 Dilute ampoules and give over 60 to 90 mins Can administer undiluted via a CVC over 90 to 120 minutes Unknown, suggest IBW +20% and check levels
Levofloxacin 500mg every 12 hours
(see BNF warnings and MHRA Drug Safety Alert (updated 22 January 2024))		 GFR (ml/min): 20 to 50: 500mg loading dose then 250mg x 2
GFR (ml/min): 10 to 20: 500mg loading then 125mg x 2
GFR (ml/min): <10: 500mg loading then 125mg x 1
CVVHD/HDF: loading 500mg then 250mg x 1		 Infusion over 60 mins Pre-made bag* (100ml) Max dose 500mg x 2
Linezolid 600mg every 12 hours No adjustments required Infusion over 30 to 120 mins Pre-made bag* (300ml) If raised MIC (4mg/ml), consider 600mg every 8 hours
Meropenem 1 to 2g every 8 hours GFR (ml/min): 10 to 25: 1g x 3
GFR (ml/min): <10: 1g x 1
CVVHD/HDF: 1g every 8 hours		 Slow IV injection OR infusion over 30 mins Slow IV injection Consider 2g every 8 hours by infusion
Metronidazole 500mg every 8 hours No adjustments required
HDF: dialysed, dose as normal
CVVHD: unknown dialysis ability, dose as normal		 Infuse over 20 mins Pre-made bag* (100ml) Unknown, max dose 1g x 4
Piperacillin/tazobactam 4·5g every 6 hours GFR (ml/min): <20: 4·5g x 2
CVVHD/HDF: 4·5g x 3		 Infusion over 3 to 4 hours Slow IV injection ABW - give 4·5g every 6 hours by infusion

*NB if fluid restricted and drug only available as pre-made bag, discuss antibiotic choices with microbiology

Editorial Information

Last reviewed: 25/08/2022

Next review date: 25/08/2025

Author(s): Antimicrobial Management Team.

Version: 2.2

Approved By: TAM Subgroup of ADTC

Reviewer name(s): Alison Macdonald, Area Antimicrobial Pharmacist.

Document Id: AMT105