Livingstone Hospital Adult Critical Care Protocol

ANTIBIOTIC PROTOCOL:
Including antifungals, antivirals: Dose and Administration in Critical Care
Not including Antiretroviral and Tuberculosis Treatment

In the critical care environment always consider a loading dose of the antibiotic as soon
as an infectious aetiology is considered, or as soon as an organism is considered to be a
pathogen. Also note the doses in this guideline are for the use in the critically ill patient
and are often off-label recommendations as accepted and recommended by the national
and international critical care physicians.

Drug Normal Renal Haemodialysis Pitfalls and Pearls

renal dysfunctio
function n:

Acyclovir Herpes GFR10-50 Dose after dialysis Please note to add Hydrocortisone
simplex give 100% in Varicella Pneumonia at dose
encephalitis of dose12- of 200mg IVI 6hourlyx48hours
(14-21days) 24hourly then 100mgIVI 6hourlyx24hrs
and other GFR<10 Then 100mg 8hourlyx24hrs, then
severe give 50% of continue to taper
varicella- dose 24
zoster hourly
infections
(7-14days):
10mg/kg IVI
8hourly

Amikacin 15mg /kg IVI AVOID Obese patients should be dosed

once daily according to IBW with correction
Amikacin* factor = IBW+
trough level [0,4x(actual body weight-ideal
(taken before body weight)]
next dose)
<1mg/litre

Amphotericin B 0,7mg-1mg/kg Pre-existing Monitor renal function, potassium,

IVI for renal failure magnesium; prolonged therapy
candidaemia does not may lead to risk of anaemia.
given as require Nephrotoxicity is usually
continuous adjusted reversible.
infusion dose but if
1,0mg- on therapy
1,5mg/kg for renal
cryptococcal function
meningitis or deteriorates
filamentous significantly
fungal an
infections echinocandin
or azole will
need to be
considered

Page 1 of 10
 Livingstone Hospital Adult Critical Care Protocol
ANTIBIOTIC PROTOCOL:
Including antifungals, antivirals: Dose and Administration in Critical Care
Not including Antiretroviral and Tuberculosis Treatment

Drug Normal Renal Haemodialysis Pitfalls and Pearls

renal fx dysfunctio
n:
Ampicillin 2g >50 CrCl: no Dose as for For E.faecalis (VSE), leads to
6hrly. (For change CrCl<10, on E.coli resistance.
suspected 30-50:6- dialysis days dose To be added for Listeria in
Listeria 2g 8hrly after dialysis, meningitis if pt. older than 50yrs,
4hrly) 10-29:8- CAPD 250mg immunocompromised, or severely
12hrly 12hrly debilitated
<10:12-
24hrs
Anidulafungin▼ Loading dose: No Can be given Newest echinocandin
200mg IVI, adjustment without regard to Do not give IV bolus
then 100mg haemo-dialysis Not studied for endocarditis,
Infusion rate: osteomyelitis and meningitis.
not to exceed Monitor LFTs, note for
1,1mg/min bronchospasm.Not for Urine, CSF,
vitreous
Azithromycin 500mg IV No No adjustment Due to lower serum levels not
daily adjustment associated with QTc prolongation
Caspofungin 70mg loading No No adjustment Mild hepatic insufficiency(Child-
dose then adjustment Pugh score 5-6) no adjustment;
50mg daily moderate hepatic
IVI if > 80kg insufficiency(Child-Pugh7-9)
then 70mg 35mg daily. C.parapsilosis may be
dailyIVI less susceptible. Not drug of
choice for UTI due to
Candidaemia( use azole or
AmphoB) Echinocandin preferred
in patients who have had recent
azole exposure, whose illness is
severe, or who are at risk to get C.
glabrata or C. krusei. Not for CSF,
vitreous infections
Note: Cephalosporins do not have enterococci/ESBL cover. Cephalosporins are an inappropriate choice for
hospital acquired infections.
Cefepime* 2g IVI stat 30-49 Dose as for Anti-pseudomonal cephalosporin
4-6g daily CrCl:1g over CrCl<10 1g active against ceftazidime resistant
over 24hrs/ 2g 30min 8hrly 24hrly, on dialysis Pseudomonas.
over 3-4 <30 CrCl: 1g day give after Has activity against MSSA.
hours, 8hrly over 30 min dialysis 4th generation cephalosporin
infusions 12hrly CAPD 1g daily
<10 CrCl: 1g
daily
Ceftaroline 600mg IVI 30-50 CrCl: 5th gen Cephalosporin. For skin
12hourly 400mg IVI and skin structure infections. For
over 60 min CAP. Covers MSSA, MRSA(not
12 hourly MRSA Pneumonia). Bacteriocidal.
Covers Strep. Pneum., Strep
pyogenes, Strep agalactiae., Klebs,
E.Coli, Haemophilus. Not active
against ESBL, enterococci,
pseudomonas, bacteroides,
atypicals. Not for osteomyelitis.
No hepatic adjustments.

Page 2 of 10
 Livingstone Hospital Adult Critical Care Protocol
ANTIBIOTIC PROTOCOL:
Including antifungals, antivirals: Dose and Administration in Critical Care
Not including Antiretroviral and Tuberculosis Treatment

Drug Normal Renal Haemodialysis Pitfalls and Pearls

renal fx dysfunctio
n:
Ceftazidime* 2g IVI stat >50 Cr Cl Dose as for CrCl Very little anti- MSSA activity.
and 6g over no dose <10, on dialysis Does not have streptococcal cover.
24hrs/ 2g change days supplement Does have anti-pseudomonal
8hrly 30-50CrCl: 1g after dialysis cover, duration 7-10 days for
1g 12hrly CAPD 500mg pseudomonas.
10-29CrCl: daily
1g 24hrly
<10 CrCl: 1g
48 hrly

Ceftriaxone* 2g IVI 12 No On dialysis days Associated with pseudo-biliary

hourly adjustment give dose after lithiasis. Has activity against
(Meningitis 2g dialysis MSSA. Caution: co-administration
12hourly) of calcium containing solutions
e.g. TPN may lead to intravascular
and pulmonary precipitation.
Cefzolin 2g IVI CrCl>50-90 1-2 gm q24-48h For MSSA cover when cloxacillin
8hourly 1-2 gm q8h (+ extra 0.5-1 gm not available
CrCl 10-50 AD)
1-2 gm q12h
CrCl <10
1-2 gm q24-
48h
Ciprofloxacin 400mg IVI as ≥ 30 no On dialysis days, Lowers seizure threshold.
infusion 8hrly. change dose after dialysis If given via NGT absorption
≤30 GFR decreased ≥30%. Good cover
400mg daily against Haemophilus, Legionella
and gram neg. rods like
Pseudomonas. Drug of choice for
shigellosis, typhoid and
uncomplicated UTIs. Less potent
against Streptococcus pneumonia
and Enterococcus faecalis. May
increase QT.
Clarithromycin 500mg IVI ≥ 30 no Dose after dialysis Interacts with Amiodarone, may
12hrly Do not change On dialysis dose increase QT interval; interacts with
give as bolus <30GFR as for GFR<30 carbamazepine increase
500mg Stat carbamazepine levels
then 250mg Interacts with cyclosporine
12-24hrly increasing levels
Interacts with statins increases risk
for rhabdomyolysis
Clindamycin 600mg IVI No No adjustment Penetrates staphylococcal
6hrly adjustment biofilms, useful adjunctive therapy
when prosthetic devices cannot be
removed. Penetrates well into
avascular infected bone.
Bacteriostatic. Rare but can cause
pseudomembranous colitis.
Reduce exotoxin production by
gram negatives. Used together
with primaquine as alternative
treatment for PCP.

Page 3 of 10
 Livingstone Hospital Adult Critical Care Protocol
ANTIBIOTIC PROTOCOL:
Including antifungals, antivirals: Dose and Administration in Critical Care
Not including Antiretroviral and Tuberculosis Treatment

Drug Normal Renal Haemodialysis Pitfalls and Pearls

renal fx dysfunctio
n
Cloxacillin 2g IVI 4hrly No No adjustment Best agent for staphylococcal
for adjustment clox.-susceptible. But note that
staphylococcal Penicillin, amoxicillin, ampicillin,
bacteraemia. Piperacillin do not cover later
See organism, but in mixed infections
Staphylococca co-amoxiclav. and cephalosporins
l protocol for will cover. Bacteriocidal inhibits
duration. bacterial cell wall synthesis.
Concurrent use of other
hepatotoxic medications with
cloxacillin ... may increase the
potential for hepatotoxicity.
Should not be routinely
administered with Erythromycin.
Co-amoxiclav 1,2g IVI 8- >30 GFR no Dose after Does not cover ESBLs.
6hourly ( if adjustment dialysis Must be given immediately after
creatinine 10-30 GFR reconstituting as it begins to
clearance is 12hrly degrade after 20 minutes.
high use <10GFR Does cover anaerobes.
6 hourly) 24hrly Avoid with hepatic impairment.
Colistin Loading eGFR 30 - 60 Intermittent Always combine with an
Critically ill ml/min give haemodialysis 1 appropriate second agent to limited
• Complete section or severe 3 MU 12- MU 12-hourly resistance. It has no gram positive
21 forms including septic 9 - 12 hourly; plus supplemental or anaerobic cover; poor
consent form MU* eGFR 10 - 30 dose of penetration to lung, pleura,
• Consent must be (12 MU for ml/min give 1 MU after each pericardium, bone and CSF.
obtained prior to 70 kg and 9 2 MU 12- episode of Several pathogens possess intrinsic
first dose (even if MU for 55 hourly; dialysis resistance to the polymyxins:
telephonic) kg patients) eGFR <10 Continuous renal Morganella sp., Proteus spp.,
Maintenance ml/min give replacement : Providencia spp., and most isolates
eGFR >60 1 MU 12- 4.5 MU 12- of Serratia spp. In addition,
ml/min 4.5 hourly hourly isolates of Brucella spp., Neisseria
MU 12- spp., Chromobacterium spp., and
hourly Burkholderia spp. are resistant,
Measures to limit colistin’s
nephrotoxicity include regular
monitoring of renal function with
appropriate dose adjustment
(especially with prolonged use),
adequate hydration and limited use
of concomitant nephrotoxic drugs.
Cotrimoxazole 20mgTMP/kg/ CrCl >30 Dose after dialysis Used for Stenotrophomonas
(TMP/SMX) day in divided ml/min: no bacteraemia in critical care. Avoid
IV 80/400mg/5ml doses 6hrly adjustment in respiratory infections as there is
IVI for sepsis CrCl 15-30 an association with MDR S.
(4 amps 6h if ml/min: Pneumonia
80/400 vial) decrease
dose by 50%
CrCl <15
ml/min: Try
to avoid if
no

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 Livingstone Hospital Adult Critical Care Protocol
ANTIBIOTIC PROTOCOL:
Including antifungals, antivirals: Dose and Administration in Critical Care
Not including Antiretroviral and Tuberculosis Treatment

alternative
use 50% of
dose
Drug Normal Renal Haemodialysis Pitfalls and Pearls
renal fx dysfunctio
n:
Daptomycin 8-10mg/kg for If GFR >40 Give after Bactericidal. Acts on biofilm. No
MRSA, VRE no haemodialysis lung penetration. No blood brain
bacteraemia adjustment If patient on barrier penetration. For
and right sided If <40 give CRRT bacteraemia and right sided
endocarditis 48 hourly 8mg/kg/day endocarditis. For SSTI. Protein
daily in binding. Side-effects; eosinophilic
critically ill pneumonia, elevated CK with
4mg/kg for prolonged use
SSTI
6mg/kg daily
for MRSA
osteomyelitis
Doripenem 1g IVI over 4 >50 CrCl no Post HD 250mg For nosocomial pneumonia and
hours 8 hrly, dose infusion over 4 VAP, complicated intra-abdominal
NOTE OFF adjustment hours infection, complicated UTI
LABEL, and 30-50 CrCl Post PD 500mg
there have give 50% of infusion over 4
been problems dose 8hrly hours
with higher 10-30 CrCl
dose
Doxycycline 100 mg Should be reserved for patients
12hourly p.o. with tick bite fever. But rather use
ciprofloxacin if patient intubated
and/or shocked. Needs to be taken
after meals with lots of water.
Drug interactions with
carbamazepine, phenytoin,
barbiturates, rifampicin
Ertapenem 1g IVI daily, ≤30 GFR Dose after dialysis Does not cover Enterococci,
in critically ill
then dose Pseudomonas or Acinetobacter.
1g 12hrly 500mg IVI Covers ESBL enterobacteraciae
daily
Erythromycin 125mg IVI 6hrly given as prokinetic. Can cause hepatotoxicity. Can cause diarrhoea.
Fidaxomicin 200mg orally Macrolide for C. difficile for initial
twice daily for episode for severe and non-severe
10 days episode. Not for recurrence.
Fluconazole 800mg IVI >50 no dose 200mg after No activity against C.krusei
daily in ICU adjustment dialysis Note drug interactions. In this unit
400mgIVI 20-50 50% there has been resistance to C
daily in of dose glabrata as well as resistance
abdominal 24hourly shown to C parapsolosis. Not drug
surgery <20 25% of of choice if non-albicans species
prophylaxsis dose daily suspected. Recommended as
see Pifalls and prophylaxis against invasive
pearls candidiasis in patients recently
operated (abdominal) and now
have recurrent perforations or
anastomotic leaks.

Page 5 of 10
 Livingstone Hospital Adult Critical Care Protocol
ANTIBIOTIC PROTOCOL:
Including antifungals, antivirals: Dose and Administration in Critical Care
Not including Antiretroviral and Tuberculosis Treatment

Drug Normal Renal Haemodialysis Pitfalls and Pearls

renal fx dysfunctio
n:
Ganciclovir Induction:5mg >50 GFR Give after dialysis Used for sight or life threatening
/kg 12hrly IVI 50% dose and give dose as CMV infection in
for 14-21days, 12-24hrly; for GFR<10 immunocompromised patients and
followed in 10-50 GFR for prevention of CMV in
most cases by 25-50% transplant patients .Neutropenia in
maintenance, 24hrly; 40%, Thrombocytopenia in 20%
but GIT CMV <10 GFR
in HIV does 25% of dose
not routinely 3 times/week
require
maintenance
Gentamycin Daily IVI: 7 AVOID TDS in infective endocarditis.
mg/kg: trough
<1mg/l (daily
level before
next dose)
Imipenem 1g IVI STAT 30-49 CrCl: Dose after dialysis Cyclosporine (↑cyclosporine
over 40-60 500mg over levels),ganciclovir(↑risk of
min then 30 min 8 seizures), valproic acid(↓seizure
1g IVI 6 hrly threshold)
hourly over <30 CrCl:
3hrs 500mg over
30 min 12
hrly
Linezolid 600mg IVI stat No adjustment No dose Bacteriostatic
bolus infusion in renal adjustment but For VRE & MRSA.
Then 600mg insufficiency, shouldbe CI in patients on MAOI, pregnant
over 12 hours CrCl administered after or lactating.
>30ml/min
as infusion haemo-dialysis in Thrombocytopenia has been
every 12 hours patients receiving reported usually related to duration
haemodialysis of therapy
Macrolides: literature supports Azithromycin, Clarithromycin and Erythromycin in treatment of biofilm
in respiratory Pseudomonal infections as in cystic fibrosis and Staphylococcal infection with devices insitu
Metronidazole 500mg IVI 8 Given with ceftriaxone for
hourly anaerobic cover or given with oral
Vancomycin for fulminan C.diff
Meropenem 2g IVI STAT 30-49 CrCl: Dose after dialysis Preferred in CNS infections
over 3-5 min then 500mg over For pneumonia and primary
2g 8 hourly over 30 min 8hrly bacteraemia
3 hours <30 CrCl:
500mg over
30min
12hrly
Micafungin 100mg/day(>40 No dose No dose Echinocandin. Bactericidal. Once
kg) or adjustment. adjustment. opened, it can be stored at 25◦C
2mg/kg/day(<40k for 48 hours in reconstituted form
g) for treatment and 96 hours in diluted form.
of invasive Protect from light.
candidiasis; Not for IV Bolus. Infuse over one
150mg/day (>40 hour.
kg) or Warning: isolated cases of
3mg/kg/day intravascular haemolysis, hepatic
(<40kg) for impairment (monitor AST/ALT);

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 Livingstone Hospital Adult Critical Care Protocol
ANTIBIOTIC PROTOCOL:
Including antifungals, antivirals: Dose and Administration in Critical Care
Not including Antiretroviral and Tuberculosis Treatment

treatment of isolated cases of renal impairment.

oesophageal 99% protein bound. Not
candidiasis; dialyzable. Interactions with
50mg/day Sirolimus, nifedipine.
(>40kg) or Not for Urine, CSF, vitreous
1mg/kg/day for infections
prophylaxis
Moxifloxacin 400mg IVI daily No change None Respiratory quinolone. Cover
same as for other quinolones
except not useful in treatment of
pseudomonas. Currently at GSH
reserved for patients with
Penicillin allergy and MDR-TB
Piperacillin– 18g daily as IVI 30-49 No ESBL cover. Consider adding
tazobactam* infusion CrCl:13,5g Amikacin if you want additional
continuous cover.
infusion
<30 CrCl: 9g
continuous
infusion
Rifampicin 10mg/kg IVI <10 give For MDR Acinetobacter and CRE.
daily 50% of dose In TB when only IV can be given
In Orthopaedic patients as
adjunctive when biofilm on
prosthesis suspected.
Teicoplanin 800mg IVI 12hrly 400mg IVI Bacteriostatic
x2 doses then 12hrly x
400mg 12hrly 1day then
daily
Tigecycline 200mg IVI stat No For complicated intra-abdominal
and 100mg- adjustment and skin infections
150MG BD in Caution in patients with severe
critically ill due liver impairment
to higher volume Treatment for Enterococcus
of distribution faecium (incl.VRE), Staph.
Aureus(MRSA, VISA, VRSA),
Clostridium diff., Acinetobacter(
incl.MDR), enterobacteraciae(
ESBL, AmpC, MBL, CRE),
anaerobes, atypical: Legionella,
Mycoplasma, Streptococci,
Listeria, Corynebacterium,
Stenotrophomonas maltophilia
NOT active against
MORGANELLA,PROTEUS,PSE
UDOMONAS and
PROVIDENTIA
Not to be given in primary
bacteraemia and not in infective
endocarditis. For skin and soft
tissue infections (SSTI), intra-
abdominal infections (IAI) and
secondary bacteraemia. In
combination with polymyxin/
rifampicin in MDR Acinetobacter .
NOT for urinary infections.

Page 7 of 10
 Livingstone Hospital Adult Critical Care Protocol
ANTIBIOTIC PROTOCOL:
Including antifungals, antivirals: Dose and Administration in Critical Care
Not including Antiretroviral and Tuberculosis Treatment

Drug Normal renal Renal Haemodialysis Pitfalls and Pearls

function dysfunctio
n:
Tobramycin Age < 30: 6 AVOID
mg/kg: trough
<1mg/ml (daily
level before next
dose)
Age 30-60:
5mg/kg
Age >60:
4mg/kg
Vancomycin 125 mg Po 6 Initial episode of C.difficile non-
(oral) hourly severe and severe for 10 days
500mg Po 6 Fulminant C.difficile with IV
hourly metronidazole
Vancomycin 500 mg in For fulminant C.difficile with ileus
(rectal) approximately
100 mL normal
saline
per rectum every
6 hours as a
retention enema.
Vancomycin 15-20mg/kg 15mg/kg Does not need to Bactericidal, but bacteriostatic if
(IVI) ABW IVI stat as slow IV - be given post [ ] <4-5 times MIC
minimum 60 min repeat levels dialysis When to suspect MRSA:
Infusion/ 1g then daily before Glycopeptide Resistance
infuse 2g daily as next dose • h-VISA :(MICs 2mg/l): reduces
24 hour infusion (maintain clinical response in HAP & VAP
(maintain trough trough level without impact on mortality
level 15-20mg/L 15-20mg/L • VISA: (MIC 4-8mg/l) modifies
or 10,4- or 10,4- cell wall to “trap”
13,86µmol/L) in 13,86µmol/ glycopeptide: increase mortality
critically ill L) • Occurs with vancomycin
patients with an exposure, esp. inadequate dose
increased volume • VRSA: (MIC 32-1024mg/l)
of distribution acquires VRE vanA gene via
may need transposon (Tn1546)
25mg/kg Only attains steady state after 20-
44 hours
Voriconazole Loading dose: IV Not Indicated for invasive candidiasis
6mg/kg every 12 recommende in non-neutropenic patients with
hours IVI ( d if CrCl other deep tissue Candida
400mg bd) <50, only infections (e.g. Candida albicans,
Maintenance in oral Candida glabrata, Candida krusei,
ICU: 4mg/kg maintenance Candida parapsilosis, Candida
every 12 hours tropicalis)

Please note both CrCl and GFR are used as references as not one entity is used in literature

*To be kept at Temperature < 25ºC

▼To be stored at 2º-8ºC

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 Livingstone Hospital Adult Critical Care Protocol
ANTIBIOTIC PROTOCOL:
Including antifungals, antivirals: Dose and Administration in Critical Care
Not including Antiretroviral and Tuberculosis Treatment

KEY:

ABW- Actual Body Weight

CAP- community acquired pneumonia

CAPD-peritoneal dialysis

CrCl-creatinine clearance

CRE-carbepenamase resistant enterobacteraciae

ESBL-extended spectrum beta lactamase

Fx- function

GFR-glomerular filtration rate

HAP-hospital acquired pneumonia

IAI-intra-abdominal infections

IBW – ideal body weight

ICU-intensive care unit

IVI-intravenous

MDR- multi drug resistant

MIC-minimum inhibitory concentration

MRSA-methicillin resistant staphylococcus aureus

MSSA-methicillin sensitive staphylococcus aureus

MDR-multiple drug resistance

P.o. - per os

SSTI-skin and soft tissue infections

UTI- urinary tract infection

VAP-ventilator acquired pneumonia

VISA-vancomycin intermediate resistant staphylococcus aureus

VRSA- vancomycin resistant staphylococcus aureus

VRE-vancomycin resistant enterococci

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 Livingstone Hospital Adult Critical Care Protocol
ANTIBIOTIC PROTOCOL:
Including antifungals, antivirals: Dose and Administration in Critical Care
Not including Antiretroviral and Tuberculosis Treatment

REFERENCES

American Journal of Medicine 2010

Antibiotic Essentials 2013
Applied Pharmacology in Anaesthesiology and Crit Care
Bariran JAC 2003
CID 2009
CID 2013
Dhand F1000 Med Rep 2012
Doribax Australian approved
Drugs on the Go Nov 2012
ESCMID Candida Guidelines Dec 2012
Front Microbiol. 2014; 5: 643
Garonzik SM, Li J, Thamlikitkul V, et al. Antimicrob Agents Chemother 2011;55(7):3284-3294.
Gilbert et al
Harigaya BMC Infect Dis 2011
Hirata et al Pharmokinetics of Antifungal Agent Micafungin 2007
IDSA MRSA Guideline2011
Khatib JAC 2011
Kuti IDSA 2007 abstract 1026
Mathew J clin Pharm Ther 1994
Mieke Carlier Population pharmacokinetics and dosing simulations of amoxicillin/clavulanic acid in critically ill patients
M Mer, G Richards Chest 1998;114;426-431
Nannini Curr Opin Pharmacol 2010
Park JAC 2012
Richardson JAC 1981
SAASP guidelines
SAMF 11th Edition
Satola J Clin Microbiol 2011
Sanford Guide, Antimicrobial Therapy 2017
Turnidge Infect Dis Clin North Am 2003
Van Hal PLoS ONE 2011
Van Hal AAC 2011

Date: August 2018

Signed:

Designation: Head: ICU

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