Quaic intensive-care-unit-empirical-anti-treatment-guidelines

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Intensive Care Unit
Empirical Antimicrobial Treatment
Guidelines
November 2010

2
Intensive Care Unit
Empirical Antimicrobial Treatment Guidelines
November 2010

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Disclaimer
This guideline is aimed at providing the clinicians of NSW intensive care units (ICU) with
recommendations to frame the development of policies and procedures related to
empirical antimicrobial therapy.
The guideline is not intended to replace the critical evaluation processes that underpin
the development of local policy and procedure nor a clinician‟s judgment in an individual
case. This document is also not intended to replace Therapeutic Guidelines: Antibiotic
version 14, 2010.
Users of this guideline should critically evaluate the content as it relates to local
circumstances and any changes in the literature that may have occurred since October
2010. In addition NSW Health clinicians should review NSW state government policy
documents to identify any directives that may relate to this clinical practice.

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Contents
Disclaimer ...............................................................................................................3
Rationale .................................................................................................................6
General Considerations...........................................................................................6
Prescribing Principles..............................................................................................7
Identification of a potential source for sepsis ...........................................................9
Detection of bloodstream events..........................................................................9
Detecting central line-associated infection .........................................................10
Other diagnostic methods for bloodstream events .............................................11
Suspected endocarditis: additional tests to consider..........................................11
Community presentations......................................................................................11
Management of sepsis, uncertain focus.............................................................12
Management of sick „immunocompromised‟ patient...........................................12
Management of suspected fungal sepsis...........................................................13
Management of respiratory tract: Community acquired pneumonia ...................14
Management of respiratory tract: Aspiration pneumonia ....................................16
Management of suspected community-acquired meningitis...............................17
Management of trauma orthopaedics and multi-trauma .....................................17
Management of urosepsis..................................................................................18
Healthcare-associated presentations ....................................................................20
Hospital Acquired Pneumonia............................................................................20
Management of early Ventilator Associated Pneumonia ...................................20
Management of late Ventilator Associated Pneumonia …………………………..20
Management of intra–abdominal sepsis.............................................................22
Management of cholecystitis or biliary sepsis………………………………….......22
Management of acute pancreatitis.....................................................................23
Document History..................................................................................................24
References............................................................................................................25

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Rationale
Prompt, appropriate, targeted antimicrobial therapy is life-saving. Patients in ICU often
receive antimicrobial therapy that is poorly chosen or is given for too many days. This
excess exposure is a potent driver of colonisation and infection by multi-resistant
bacteria and Clostridium difficile. Prescribed treatment is often empirical and early
decisions to shift to directed therapy or cessation of therapy can reduce antibiotic
exposure significantly. Reduction in antimicrobial exposure leads to reductions in
resistance and less cost. Controlling resistance selection within the ICU has potential
spill-over effects for the general hospital.
General Considerations
Empirical antimicrobial choice should be guided by Therapeutic Guidelines: Antibiotic
version 14, 2010 (Antibiotic Guidelines 14)1
. The drug recommendations in this
document are based on those in Antibiotic Guidelines 14 with variations to reflect
local practice. Only adult doses are provided in this document. Consult Antibiotic
Guidelines 14 for paediatric doses.
In ICU fluid resuscitation and source control are as important as appropriate
antimicrobial prescribing2
.
Time to antibiotic administration should be minimised in severe sepsis. It is
suggested that within 1 hour from triage is a reasonable target (in one recent large
retrospective study, every additional hour to effective antimicrobial initiation in the
first 6 hours after the onset of hypotension was associated with >7% decrease in
survival3
).
Ensure there are processes in place for clear communication of urgent information
between the laboratory and treating medical officers.
Limit the duration of antibiotic therapy when clinically appropriate to minimise the
opportunity for the emergence or selection of multi-drug resistant organisms
(MDRO's) and Clostridium difficile infection. This is particularly relevant to elective
surgical antibiotic prophylaxis where clinicians should be vigilant to ensure
appropriate and timely cessation of antibiotics – a single dose is indicated for nearly
all types of surgery (see Antibiotic Guidelines 14). Trauma patients may require more
prolonged treatment.
Where an aminoglycoside is given for empirical treatment, a maximum of 48 hours is
recommend (equating to 3 daily doses in patients with eGFR > 60mL/min and 1-2
doses in patients with degrees of renal failure) (see Table 24 and 25 from Antibiotic
Guidelines 14, reproduced in table 1 and 2 below). If ongoing aerobic Gram negative
cover is required, then treat with a non-aminoglycoside agent based on organism ID
and susceptibilities if known.

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Prescribing Principles
To ensure that appropriate prescribing is supported in the intensive care setting
adherence to the following principles based on the AIMED model4
are encouraged.
Figure 1: AIMED ANTIMICROBIAL PRESCRIBING MODEL
Select empiric agents in accordance with Antibiotic Guidelines 14 and local
antibiogram data.
Seek Infectious diseases physician /Microbiologist input as required (eg: life
threatening penicillin allergy5
and de-escalation of therapy).
Investigate patients appropriately prior to antimicrobial treatment if possible. See
identification of a potential source and detection of bloodstream events below.
De-escalate or streamline antimicrobial treatment at 48 hrs based on the clinical
picture and relevant microbiological results- where necessary obtain specialist
advice.
Limit duration of therapy according to clinical response, ultimate diagnosis and
available evidence by specifying the indication, evaluating at 48 hrs and
documenting a specific duration or review date for every antimicrobial course.
Consider IV to oral switch as soon as clinically feasible.
Ensure patients discharged from ICU with antimicrobials still prescribed have a
review date provided in the discharge summary.
When prescribing certain agents the need for ongoing therapeutic drug monitoring
should be considered (see Antibiotic Guidelines 14).
Aminoglycosides if used beyond 72 hours to detect accumulation.
Vancomycin to ensure adequacy of dosing. Adjust dose according to renal function to
achieve recommended concentration. For intermittent dosing the target trough
concentration is 12–18 mg/L. For continuous infusion the target concentration is 17–23
mg/L.
If impending renal failure an issue avoid more than 1 dose of gentamicin and
consider an antipseudomonal beta-lactam such as ticarcillin/ clavulanate or
piperacillin/tazobactam as an alternative5
.
If sepsis develops when patient has been on antibiotics for more than 48hrs, discuss
with an infectious disease physician or microbiologist before changing drugs5
.

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Tables 1 and 2 have been adapted with permission from Antibiotic Expert Group, Therapeutic
guidelines: antibiotic, Version 14, Melbourne: Therapeutic Guidelines Limited; 2010, p 360
Table 1: INITIAL AMINOGLYCOSIDE DOSE FOR EMPIRICAL AND DIRECTED THERAPY
1
Age Initial gentamicin/ tobramycin dose [NB1]
10–29 years 6 mg/kg up to 560 mg
30 to 60 years 5 mg/kg up to 480 mg
More than 60 years 4 mg/kg up to 400 mg
10 years or more with severe sepsis
(sepsis syndrome) [NB2]
7 mg/kg up to 640 mg
Any age with streptococcal and
enterococcal endocarditis
3 mg/kg/day [NB3] (use gentamicin only, in
divided doses)
NB1: For subsequent empirical dosing, see Table 2. For subsequent directed dosing,
see Antibiotic Guidelines 14, p 361.
NB2: Patients with severe sepsis have higher volumes of distribution and therefore
require a higher mg/kg dose.
NB3: Lower doses are used for synergistic treatment in endocarditis (see Streptococcal
endocarditis p 57 and Enterococcal endocarditis p 59 in Antibiotic Guidelines 14).
Table 2: AMINOGLYCOSIDE DOSING INTERVAL FOR SUBSEQUENT EMPIRICAL DOSES
1
Creatinine clearance [NB4] Dosing interval doses as
above
Maximum empiric doses
Greater than 60 mL/min 24 hours 3 (at 0, 24 and 48 hours)
40–60 mL/min 36 hours 2 (0 and 36 hours)
30–40 mL/min 48 hours 2 (0 and 48 hours)
Less than 30 mL/min Give initial dose then seek expert advice
NB4: Creatinine clearance estimate should be based on a creatinine measurement
obtained as recently as possible (eg within the last 12 to 24 hours); however, this might
still overestimate renal function in acute renal failure.

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Identification of a potential source for sepsis
Comprehensive physical assessment including examination of: skin, ulcers, inserted
vascular lines and drains, wounds, sinuses, ears, teeth, throat, chest, cardiovascular
system, back, abdomen, perianal, genital/ reproductive, urinary, bones and joints
including spine and for signs of meningism.
Collect blood cultures, sputum, urine specimens.
Culture cutaneous wounds, lesions, invasive devices ulcers, pressure areas
Consider bronchoalveolar lavage, sampling cerebral spinal fluid, pleural fluid,
abdominal collections, stool culture, skin biopsy as clinically appropriate
Obtain x-rays, CT Scans, surgical consultation as clinically appropriate
Mark sterile samples appropriately to ensure prompt laboratory assessment
Where appropriate, also consider non-infective causes of fever or systemic
inflammatory responses such as:
o central cause (eg. Head injured or ICH patient)
o drugs/medications
o pulmonary embolism
o autoimmune disease; e.g. temporal arteritis
o neuroleptic malignant syndrome
o malignancy
o ischaemic gut or other ischaemic tissue
o pyrogens (e.g. from sterile haematoma in pleural, retroperitoneal or pelvic
spaces)
o factitious disease
Detection of bloodstream events5
Detection of bacteraemia or fungaemia in adults is highly dependent on volume of blood
added to blood culture bottles6
. To ensure optimal blood culture collection from septic
patients the following practice is recommended: 5, 7– 9
Collect 2 blood culture sets (a total of 40mL – at least 10mL per bottle –) from
separate venepunctures within 48 hrs to evaluate each sepsis episode9
. In some
circumstances an additional anaerobic bottle may be collected (e.g. neutropaenia,
abdo/pelvic surgery, long term invasive devices in situ)
A blood culture set comprises 2 bottles (aerobic and anaerobic) in an adult or 1
paediatric bottle in infant/ small child although an anaerobic bottle should be added if
anaerobic sepsis is considered a diagnostic possibility (eg neutropenia,
abdominal/pelvic surgery).
Adult: for nearly all systems, 8-10mLs of blood is required for each bottle (avoid
over-filling as it renders the culture less sensitive)
Paediatric: generally 0.5–4mLs required (consult local laboratory)

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Routine collection via old or new central or arterial lines is not recommended due to
the potential for contamination from hub and/or contamination of line. Lines may
have internal colonisation without the patient having systemic sepsis. Studies
evaluating the isolation of coagulase negative staphylococci from blood cultures
collected via lines indicate false positivity in a significant proportion .10–11
Discuss the
diagnostic methods available for catheter-associated infection with the
Microbiologist.
Use aseptic collection technique in order to avoid contamination and maximise
specificity5
:
o Collectors should perform hand hygiene and use personal protective
equipment.
o Disinfect skin and top of blood culture bottles with alcohol with
chlorhexidine 2% and wait for it to dry
o Use no-touch needle insertion (many places specify use of sterile gloves)
o Use vacutainer sleeve with leash for blood culture bottle (safety issue)
o Do not change needle after collection before bottle inoculation (minimal
effect on contamination rates and creates a safety issue)
Persistently febrile patients (eg. neurosurgical) should have regular blood cultures (e.g.
every 48 hrs) to detect line-associated sepsis.
Detecting central line-associated infection (for clinical purposes)5
Ensure appropriate blood culture collection when indicated and ensure appropriate
audit of results to detect central line-associated events.
Examine line exit sites daily for exudate and/or inflammation.
Line-drawn cultures (see cautions above) may be considered in addition to those
collected by venipuncture, provided that they are clearly labelled and interpreted as
such. The diagnostic significance of a line positive / venipuncture negative result,
particularly for common contaminants, will rarely be clear. If line drawn cultures are
used to diagnose line sepsis, request differential quantitative cultures where
available (see other diagnostic methods below)
If line sepsis suspected, collect 2 sets of blood cultures by peripheral venipuncture. If
alternate venous access is feasible remove the line and submit the aseptically
collected tip for semi-quantitative culture. According to a 2005 metanalysis12
;
isolation of 15 or more colonies has 75-84% sensitivity for detection of a true line-
associated infection. Line tip cultures may be falsely negative if microbial
contamination is predominantly intraluminal. Conversely, the estimated specificity of
a positive line tip result is between 71-85%. Isolation of less than 15 colonies from
the tip usually represents contamination of the line by skin flora during removal and
should be generally disregarded. NB. Culture of line tips in asymptomatic patients,
where the line is removed for reasons other than suspected sepsis, is not
recommended13
.
If pathogens are isolated from a line tip culture and coincident blood cultures are
negative, then clinical evaluation should occur to determine whether antimicrobial
treatment is required. In general coagulase negative staph. isolated from line tip will
not require further treatment.

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Other diagnostic methods for bloodstream events
Other diagnostic methods are detailed in the referenced metanalysis12
. Differential
quantitative cultures or differential time to positivity (peripheral blood versus blood
collected via central line) has the disadvantage of requiring blood withdrawal via the
central line with the potential for line contamination. It is a feasible approach for dialysis
lines, although one then has to ensure that all line lumens are sampled; another
complication for the process. There are other potential practical barriers to the success
of this method, in particular ensuring equivalent blood volumes from each sampling site,
and “parallel” handling of samples. Consultation with local laboratories regarding the
feasibility of this technique may be required.
Suspected endocarditis (culture negative): additional tests to consider4
Additional blood cultures (optimum 3 sets if no recent antibiotic exposure; 6 sets if
given antibiotics within the last 30 days)
Serology for Bartonella species and Coxiella burnetii (Q-fever) unless explanted
valve tissue or skin biopsy is available in which case nucleic acid amplification test
(polymerase chain reaction-PCR) should also be performed for these pathogens14
C. burnetti, B. quintana and B. henselae are by far the commonest causes of culture
negative endocarditis in patients who have not been exposed to antibiotics14
.
Community presentations
Community presentations encompass patients that are symptomatic on admission or
within 48 hours of admission. In general, consult Antibiotic Guidelines 14 for treatment
recommendations in accord with likely source of sepsis and local epidemiology of
antimicrobial resistance. Selected syndromes are highlighted below.
Risk factors for MDRO include15
:
indwelling percutaneous medical devices or catheters
visits to high-prevalence country within the past 3-6 months (e.g. India has 70-90%
ESBL rates in E. coli)
Additional risk factors reported in the literature of mostly US publications are16
:
recent hospitalization or surgery (previous 12-24 months)
residence in a long-term care facility
dialysis
prolonged or previous antimicrobial use

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Management of sepsis, uncertain focus
Empiric treatment1
Regimen Drug Dose
1 flucloxacillin 2g IV 6 hourly
gentamicin 7mg/kg for 1 dose, then
determine dosing interval
for a maximum of either 1
or 2 further doses based on
renal function (see Tables 1
and 2)
Special circumstances
In cases presenting with
shock to provide MRSA
cover, add
vancomycin 1.5g IV 12 hourly (adjust
initial dosage for renal
function, and subsequent
doses to achieve
therapeutic range
(Antibiotic Guidelines 14
Table 26 p365). For
information on continuous
infusion, see Antibiotic
Guidelines 14 p365.
For patients with suspected
meningococcal sepsis, add
benzylpenicillin 1.8g IV 4 hourly
In patients with hypersensitivities see Antibiotic Guidelines 14
Management of sick „immunocompromised‟ patient (febrile
neutropaenia)
Neutropaenic patients may present without fever, however, a patient receiving
chemotherapy, whether known to be neutropaenic or not, who presents with fever,
chills, rigors or unwell should receive empiric antibiotic therapy without waiting for the
results of investigations to become available.
Consider previous antimicrobial exposure and prior microbiology to guide empiric
selection.
Consultation with the patient‟s haematologist or oncologist is recommended
Diagnostic Work-up
Aggressive diagnostic workup that includes tests for typical and atypical bacteria,
viruses, parasites and fungi as appropriate.

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Empiric treatment1
Regimen Drug Dose
1 piperacillin /tazobactam 4+0.5g IV 8 hourly
or
In patients with minor
penicillin hypersensitivity,
use
ceftazidime 2g IV 8 hourly
In patients in shock or
known to be colonised with
methicillin-resistant
Staphylococcus aureus
(MRSA) or has clinical
evidence of a catheter-
related infection in a unit
with a high incidence of
MRSA infection add
doses to achieve
therapeutic range
Table 26 p365). For
Guidelines 14 p365.
Management of suspected fungal sepsis
Refer to Antibiotic Guidelines 14
Empiric treatment1
Regimen Drug Dose
1 Azole naïve, No prior
isolates of Candida glabrata
or C. kruzei:
fluconazole 800mg IV first dose and
then 400mg IV daily
or
2 amphotericin B 0.5 to 1.0mg/kg IV daily
or
3 caspofungin 70mg IV first dose, then
50mg IV daily

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Management of respiratory tract: Community acquired pneumonia
(CAP)
Assessment
Explicitly score the severity of pneumonia. There are a number of tools available that
are useful in stratifying patients likely to require ICU management.– CORB or
SMART-COP pneumonia severity assessment tools are, recommended in Antibiotic
Guidelines 14)
Ensure that severe pneumonia is investigated comprehensively- see example
Checklist for severe/ICU community acquired pneumonia investigation (protocols
such as this should be discussed with your Clinical Microbiology Service before
finalisation).
Diagnostic Work-up
Sputum for Gram stain and culture and blood cultures17
In severe pneumonia, send at least 2 blood cultures, consider urinary antigens
testing for Legionella pneumophila type 1 and Streptococcus pneumoniae and a
nasopharyngeal or BAL for respiratory virus and Legionella detection.
In significant pleural effusions or suspected empyema, aspiration for diagnostic +/-
therapeutic purposes should be considered. Pneumococcal antigen testing on
empyema fluid and urine, if available, may be a useful adjunct to conventional culture
in patients already receiving antibiotics.
Empirical treatment1
Initial broad spectrum antimicrobials that provide coverage against S. pneumoniae,
Legionella species and aerobic Gram negatives are used.
Note for Streptococcus pneumoniae there is no evidence that betalactam resistance
alters the outcome in the absence of CNS involvement: Intravenous benzylpenicillin
remains the drug of choice unless the MIC to penicillin is >= 8mg/L (isolates with
MIC> 2 are rarely found in Australia)18
.
In bacteraemic pneumococcal disease with shock a possible benefit from additional
macrolide therapy is probably due to immunomodulatory effects rather than anti-
bacterial effects19-20
.

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Regimen Drug Dose
1 benzylpenicillin 1.2g IV 4 hourly
azithromycin 500mg IV daily
gentamicin 4-6mg/kg (severe sepsis :
7mg/kg) for 1 dose, then
and 2)
or
2 ceftriaxone 1g IV daily
or
In patients with immediate
penicillin hypersensitivity
moxifloxacin NB1 and NB2 400mg IV daily
NB1: Extra caution should be exercised when agents that prolong QT interval such as
amiodarone are being administered
NB2: Excessive fluoroquinolone use may be associated with selection of MRSA and
quinolone-resistant C. difficile.
In any patient with
suspected staphylococcal
pneumonia from Gram stain
of sputum, clinical picture,
radiographic appearance
and/or initial blood culture
result) add
doses to achieve
therapeutic range
Table 26 p365). For
Guidelines 14 p365.
In any patient with severe
pneumonia with a clinical
presentation consistent with
severe influenza, during a
period where Influenza A is
known to be circulating
consider neuramindase
inhibitor (oseltamivir,
zanamivir)
150mg via nasogastric tube
twice daily

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Management of respiratory tract: Aspiration pneumonia (eg. post
cardiac arrest)
Empirical treatment1
Regimen Drug Dose
metronidazole 500mg IV 12 hourly
or
In patients with immediate
penicillin hypersensitivity as
single agent use either
lincomycin or 600mg IV 8 hourly
clindamycin 450mg IV 8 hourly
In patients where aerobic
Gram negatives are
suspected (eg. in alcoholic
patient) add
(Recommendation by QUAIC
Expert Advisory Group not
Antibiotic Guidelines 14)
and 2)
In patients with known or
suspected pseudomonal
pneumonia
(eg. bronchiectasis with
past pseudomonal
colonisation) NB1
piperacillin /tazobactam 4+0.5g IV 6 hourly
and 2)
or
substitute
piperacillin+tazobactam
with
ceftazidime 2g IV 8 hourly
NB1: Use two active drugs initially, especially if bacteraemia is present. For severely ill
patients, infusing each dose of the piperacillin+tazobactam over 4 hrs may achieve
better outcomes.

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Management of suspected community-acquired meningitis
Give steroids (dexamethasone10mg, IV) with first dose of antibiotics then 6 hourly for
four days.
Empiric treatment1
Regimen Drug Dose
2 cefotaxime 2g IV 6 hourly
where there is a risk of
Listeria i.e. very young,
pregnant, or
immunosuppressed add
benzylpenicillin 2.4g IV 4 hourly
if herpes simplex
encephalitic picture
acyclovir 10mg/kg IV 8 hourly for at
least 14 days
Management of trauma orthopaedics and multi-trauma
If a fracture is debrided, fixed and closed within 6 hours or an external fixature is
present, a prophylactic dose of the antibiotic (as per the regimen below) is given with no
further doses required. Most cases are considered to be already infected with no
symptoms present. In these cases presumptive empiric therapy as per the Gustillo
classification in table 3 is recommended. Type I fractures within this classification system
has a low risk of infection whereas fractures classified as type IIIC have a 50% chance
of infection.
Empiric treatment
Regimen Drug Dose
Orthopaedics Non-elective
Trauma
cefazolin 2g IV 8 hourly
or
Orthopaedics Non-elective
Trauma
doses to achieve
therapeutic range
Table 26 p365). For
Guidelines 14 p365.

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Table 3: GUSTILLO CLASSIFICATION OF OPEN FRACTURES
21
Gustillo Type Fracture size Duration of therapy
I Less than 1cm 24 hours after wound
closure or 2 days for open
wounds
II 1–3 cm 24 hours after wound
wounds
III Greater than 3 cm 24 hours after wound
wounds
III A Greater than 3 cm, bone
coverable
24 hours after wound
wounds
III B Greater than 3 cm, bone
not coverable
wounds
III C Greater than 3 cm, arterial
injury, bone not coverable
wounds
Other multi–trauma including brain injury, base of skull
fracture and CSF monitoring in place
24 hours (3 doses)
Management of urosepsis
Escherichia coli is responsible for most cases of complicated and uncomplicated
urosepsis. Other organisms including Staphylococcus saprophyticus, Proteus,
Klebsiella, enterococci and Streptococcus agalactiae (group B streptococcus) may also
be cultured.
Urinary catheters are common in critical care and asymptomatic bacteriuria and /or
pyuria or abnormal urinalysis should not be treated routinely with antimicrobials.
Treatment is required where signs of systemic infection exist or significant risk factors
such as neutropenia, transplantation or pregnancy are present.
If possible, the indwelling catheter should be removed as a form of source control.
Where a catheter is required for ongoing management the catheter should be changed
and a sample collected from the new catheter prior to antimicrobial therapy.

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Diagnostic Work-up
urine and blood cultures
Cultures taken from indwelling catheters are unreliable due to the presence of
biofilms/colonisation in the catheter lumen and should be collected from a newly inserted
catheter.
Empiric treatment1
Regimen Drug Dose
1 ampicillin 2g IV 6 hourly
and 2)
Uncomplicated IDC-related infections (without bacteraemia) can be managed with short
course treatment (5 days) targeted against demonstrated organism. UTI complicated by
bacteraemia, treat for longer 7-10 days, dependent on presence of pyelonephritis and/or
urinary tract obstruction. Early conversion to oral therapy is possible if bacteraemia is
absent1
.

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Healthcare-associated presentations (high risk of
MDRO or known MDRO colonisation)
Hospital Acquired Pneumonia
Recommended assessment
Diagnostic criteria are relatively non specific and there is no gold standard for
achieving a reliable diagnosis.
For practical purposes HAP is divided into early (onset within 5 days of admission)
and late (5 days or more) due to differences in the microbiology of pneumonia.
Diagnostic tests to identify the causative organism should be performed prior to
antibiotics, especially in VAP.
Diagnostic Work-up
Sputum (consider collection by bronchial lavage), blood, urine and
Perform CXR+/- CT22
Management of early Ventilator Associated Pneumonia (VAP)
(provided no known colonisation with MRO):
Empiric treatment1
Regimen Drug Dose
and 2)
or

21
Management of late VAP
Consider previous antibiotic exposure and previous culture results before selection of
regimen.
Empiric treatment1
Regimen Drug Dose
1 piperacillin /tazobactam 4+0.5g IV 6 hourly NB1
If the patient is ventilated,
for a maximum of 48 hrs,
add
and 2)
use as single agent
cefepime 2g IV 8 hourly
If MRSA colonised, add vancomycin 1.5g IV 12 hourly (adjust
doses to achieve
therapeutic range
Table 26 p365). For
Guidelines 14 p365.
NB1: For severely ill patients, infusing each dose of the piperacillin+tazobactam over 4
hrs may achieve better outcomes.
NB2: Review all cases at 3 days to assess response to treatment, likely microbial cause
(if any) and alternative diagnoses. If rapid response to treatment or an alternative non-
infective diagnosis likely, then cease antibiotics at 3 days. Otherwise continue treatment
directed against the demonstrated pathogen(s) for 7-8 days. Pseudomonal infection is
usually treated for longer.
NB3: Candida are not considered to have an important role in causing VAP. Non
bacterial causes of fever and pulmonary infiltrate need to be considered in the
appropriate contexts: HSV, CMV, Aspergillus. Nosocomial Legionella may also require
consideration in some circumstances.

22
Management of intra–abdominal sepsis
Empiric treatment1
Regimen Drug Dose
1 NB1 ampicillin 1g IV 6hourly
and 2)
If still septic, evaluate
source control and,
dependent on
intraoperative or other
microbiology results,
change to mono-therapy
with either:
piperacillin /tazobactam 4+0.5g IV 6 hourly
ticarcillin /clavulanate 3+0.1g IV 6 hourly
NB1: Re-evaluate patient at 48-72 hrs. If source dealt with by surgery (eg. closure of
perforation and peritoneal lavage) and post-operative course uncomplicated by ongoing
sepsis, then cease gentamicin and continue other drugs up a total duration of 5 days.
NB2: If Candida species isolated from intraoperative specimen(s) consider addition of
antifungal therapy as well (usually for 2 weeks).

23
Management of cholecystitis or biliary sepsis
Causative organisms of acute cholecystitis are usually aerobic bowel flora (eg
Escherichia coli, Klebsiella species and, less commonly, Enterococcus faecalis).
Anaerobes are found infrequently, unless biliary obstruction is present. A laparoscopic
cholecystectomy should be considered during the presenting admission.
Empiric treatment1
Regimen Drug Dose
1 ampicillin 1g IV 6 hourly
and 2)
If biliary obstruction is
present, to treat anaerobes
add
Management of acute pancreatitis
Prophylaxis to prevent pancreatic infection is not recommended. Treatment of choice for
infected necrosis is surgical debridement. Patients with severe pancreatitis may appear
septic clinically at various times during a prolonged hospitalisation. Before giving
antibiotics, it is best practice to perform image-guided percutaneous aspiration.
Empiric treatment1
Regimen Drug Dose
1 piperacillin /tazobactam 4+0.5g IV 8 hourly

24
Document History
Document Version Document development Date
Draft ICU
Guidelines for
Empirical
Antimicrobial
Treatment
0.1-0.3 Modified by the QUAIC Expert Advisory
Group from Draft July 6 2004
Recommendations for First Line
Antibiotic Therapy in the ICU, Nepean
Hospital
Sep 2009–
Aug 2010
Draft 0.4-0.6 Modified based on feedback from the
QUAIC Expert Advisory Group
Aug–Sep
2010
Draft 0.7-0.7a Modified based on feedback from the
QUAIC Expert Advisory Group and
Therapeutic Guidelines: Antibiotic 14
2010
Oct 2010
Final 1.0 Additional material added and minor
errors corrected
Nov 2010

25
References
1. Antibiotic Expert Group, Therapeutic guidelines: antibiotic, Version 14, Melbourne:
Therapeutic Guidelines Limited; 2010
2. Royal Adelaide Hospital ICU Medical Manual 2010 accessed 30 March 2010
3. Kumar, A., et al., Duration of hypotension before initiation of effective antimicrobial therapy is
the critical determinant of survival in human septic shock. Critical Care Medicine, 2006. 34(6):
p. 1589-96.
4. Healthcare Infection Control Special Interest Group, A I M E D: 5 principles of good
antimicrobial prescribing practice, accessed October 2010
5. Healthcare Infection Control Special Interest Group, Detection of Bloodstream events
accessed 30 March 2010
6. Li J, Plorde JJ and Carlson LG, Effects of volume and periodicity on blood cultures, Journal of
Clinical Microbiology, Nov. 1994, p. 2829-283, accessed from Detection of Bloodstream
events, 30 March 2010
7. The NSW Health HAI Clinical Indicator Manual, Nov 2008, accessed 30 March 2010
8. Taking Blood Cultures by Syringe, Wentworth Area Health Service, ICU Protocol Committee
April 2004
9. Lee A, Mirrett S, Reller LB, Weinstein MP. Detection of bloodstream infections in adults: how
many blood cultures are needed? J Clin Microbiol. 2007 Nov;45 (11):3546-8.
10. Updated review on blood culture contamination Hall Clin Micro Reviews 2006
11. Sherertz R, et al, 2010, Blood Cultures drawn through valved catheter hubs have a 10-20%
positivity rate with the majority being false positives, Abstract 437, Fifth Decennial
International Conference on Healthcare Associated infections
12. Meta-analysis: methods for diagnosing intravascular device-related bloodstream infection
2005
13. Maki original 1977 paper on roll-tip line culture for diagnosis Still the commonest method in
use
14. Houpikian P, Raoult D. Blood culture-negative endocarditis in a reference center: etiologic
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Intensive Care Med, 36:562–564
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26
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GPO Box 1614
Sydney NSW 2000
Tel 61 2 9382 7600
Fax 61 2 9382 7615
www.cec.health.nsw.gov.au
Offices
Level 3, 65 Martin Place
Sydney NSW 2000
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Sydney NSW 2000

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