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The rapid in-ICU emergence and dissemination of multi-drug resistant microorganisms worldwide
constitute a problem linked directly to inappropriate antimicrobial use.

Time to appropriate antibiotic administration is a major outcome determinant for ICU patients
with severe bacterial infections

Each hour of delay in administering effective antibiotics for septic shock is associated with
increased mortality

Obtaining biological specimens should not postpone timely antibiotic administration to patients
with severe sepsis or septic shock
RATIONAL ANTIBIOTIC USE

Using Pk-Pd
Rapid Identification of characteristics to
Better empirical
patients with bacterial optimize antibiotic
treatment selection
infections dosing and
administration

De-escalation once Reducing numbers of

Shortening therapy
culture results are patients treated
duration
available unnecessarily
RATIONAL ANTIBIOTIC USE: CHALLENGES
Complex decision-
Infection severity
making process
often precludes
frequently involves
withdrawing or
doctors with limited
postponing antibiotics
expertise

Difficult to ensure
disease-long
continuity of care by
the same medical team
24/7
 FACTORS INFLUENCING SELECTION OF
ANTIBIOTIC
Disease Factors Host Factors Organism Factors Drug Factors
• Travel history • Age • Susceptibility • Cost
• Occupation • Clearance • Biology • Toxicity
• Recreational • Genetic variation • Source control • Bioavailability
exposure • Pregnancy and • Duration of • Site penetration
• Recent antibiotic lactation therapy • Bactericidal vs
use • Immuno- • Assessment of bacteriostatic
• Empiric vs competence response • Synergistic
definitive • Allergies combination
• Severity of illness
• Urgency and
timing
• Reliability of
cultures
 SELECTION OF INITIAL ANTIBIOTIC THERAPY
ICU patients with clinically suspected HAIs
 Empirical broad-spectrum antibiotics
 Regimen choice should be based on:
 Local antimicrobial susceptibility patterns
 Anticipated side effects
 Consideration of antibiotics received within the preceeding 2 weeks, and try whenever possible
not to use same class
 Observational study results confirmed that initial regimens combining a broad-spectrum B-lactam
and an aminoglycoside increased the proportion of appropriately treated patients compared with
monotherapy or a combination of B-lactam and flouroquinolone
 Patients with mildly or moderately severe, early-onset infections and no specific risk factors can
receive a relatively narrow-spectrum drug (eg: third generation cephalosporin)
SELECTION OF INITIAL ANTIBIOTIC THERAPY
ICU patients with Health Care Associated or Community Acquired Infections
 More restraint for antimicrobial therapy is possible
 Current criteria for health care associated pneumonia:
 Hospitalization for at least 2 days during the preceding 90 days
 Residence in a nursing home or extended care facility
 Home IV therapy (antibiotics or chemotherapy)
 Chronic dialysis
 Home wound care during the preceding 30 days
 Use of the above criteria as indications for broad spectrum antibiotics may lead to
overtreatment of many patients with pneumonia.
PK-PD OPTIMIZED THERAPY
 There is a need to individually adjust the antibiotic target doses and administration
modalities to treat severe bacterial infection adjusted to
 Patient’s pharmacokinetics
 Patient’s documented pathogens’ susceptability, as assessed by their Minimal
Inhibitory Concentration (MIC)

 Most distinguish antimicrobials by their killing mechanism:

 Concentration-dependent
 Time-dependent
 Antimicrobial Characteristics related to Pk/Pd Behaviour

1) Concentration dependent killing activity and moderate to prolonged

persistent effects (Cmax/MIC, AUC/MIC)
Aminoglycosides
Fluoroquinolones
Metronidazole
Colistin
Rifampicin
Clindamycin
2) Time dependent killing activity and minimal persistent effects (T>MIC)
Beta lactams
Linezolid
3) Time dependent killing activity and moderate to prolonged persistent
effects (AUC/MIC)
Tetracyclines
Vancomycin
The spectrum of critical illness-related altered pathophysiology and its effects on drug
concentrations.
CVS
 Fluid shifts, ‘third spacing’ and fluid overload
 Leads to changes in Vd
 Affects Hydrophilic antibiotics (aminoglycosides, B-lactams, glycopeptides and
linezolid)
 Hypoalbuminaemia
 With decreasing albumin concentrations, increased unbound fraction of protein bound
drugs can occur
 Vd for moderate to highly-protein bound antibiotics including ceftriaxone,
flucloxacilling, ertapenem and daptomycin are found to increase by up to 100% in
critically ill patients with hypoalbuminaemia
 Fluid shifts and altered protein binding will both increase Vd
 Increased Vd reduces the peak concentration of drugs which is problematic for
antibiotics exhibiting concentration dependent effects (eg: aminoglycosides)
CVS
 Tissue perfusion and target site distribution of antibiotics
 Effective antibiotic concentrations need to be achieved in the interstitial fluid of
tissues
 This is the site of most infections
 Sepsis can cause vascular dysfunction, microvascular failure which can impair drug
delivery into body tissues
 Impaired tissue penetration in early phase of treatment
 Piperacillin, levofloxacin
Renal
 Augmented Renal Clearance (ARC)
 Udy et al, demonstrated up to 82% of patients demonstrating ARC will not achieve
therapeutic antibiotic concentrations with standard antibiotic doses
 Renal dysfunction
 Will require appropriate dose decreases to ensure therapeutic and non-toxic
antibiotic exposure
 However, large dose decreases are not required in the presence of AKI for antibiotics
with a wide therapeutic index and where clearance occurs by multiple routes
 Ceftriaxone, Flucloxacillin, Ciprofloxacin- have both hepatic and renal clearance
pathways
Renal
 Renal Replacement Therapy
 In general, drugs that are poorly eliminated by RRT
 High Vd (>1L/kg)
 Lipophylic drugs
 Drugs with high protein binding (>80%)
Pulmonary system
 Pneumonia is the most common infection in critically ill patients
 Important cause of morbidity and mortality in ICU patients
 Providing optimal antibiotic exposure for HAP in ventilated patients is challenging
 Due to various patient, pathology and drug factors that can affect drug concentration
to the site of infection.
 Alveolar compartments
 Epithelial Lining Fluid (ELF) are considered the closest measurable site where
extracellular pathogens accumulate
 Optimal antibiotic concentrations in this area may determine therapeutic success
Pulmonary System
 Following systemic drug administration, the antibiotic must cross the alveolar capillary
barrier to exert activity within the ELF
 Passage across the barrier influenced by:
 Drug pharmacology
 Lipophilicity
 Protein binding
 Patient specific characteristics
 Inflammation
 Chronic Lung Disease
 In general, while blood concentrations may appear “therapeutic”, ELF concentrations
may be insufficient for optimal antibiotic treatment, especially in the case of reduced
bacterial susceptability
Hepatic system
 Hepatic dysfunction may also cause a decrease in drug metabolism and clearance
 However, to date, few data available to guide antibiotic dose adjustments in critically ill
patients with liver dysfunction, regardless of critical illness.
MINIMAL INHIBITORY CONCENTRATION
- Lowest concentration of an antimicrobial that will inhibit the visible growth of a
microorganism following overnight incubation, usually reported as mg/L
- A related concept is the minimum bactericidal concentrations (MBCs), which is
the lowest concentration of antimicrobial that will prevent the growth of an
organism after subculture on to antibiotic-free media
- Importance:
- defines the drug exposure necessary to ensure a patient achieves a predefined PK/PD
target that is associated with maximal efficacy
- research tool to determine the in vitro activity of new antimicrobials and determine
‘MIC breakpoints’
- monitor resistance to antimicrobial agents
- Determination:
- by agar or broth dilution methods
- strips with graded changes in antibiotic concentrations provided
- when placed on plates the point at which the bacterial inhibition intersects with
strip is the MIC
MINIMAL INHIBITORY CONCENTRATION
CLINICAL APPLICATION
 generally drug concentrations need to be 4-5x the MIC to ensure that an antibiotic is
effective
 different antibiotics depend on Cmax, AUC above MIC and time above MIC for
maximal effect
 most laboratories routinely report susceptibility with the classification ‘S, I and R’
(Susceptible, Intermediate-Susceptible and Resistant) based on MIC breakpoints
 The breakpoint is the chosen concentration of an antibiotic which defines whether a
species of bacteria is susceptible or resistant to the antibiotic
 If the MIC is less than or equal to the susceptibility breakpoint the bacteria is
considered susceptible to the antibiotic
Infection and Chemotherapy: Vol 40, No 3, 2008
 Fig 3

BJA Education 2017 17, 111-116DOI: (10.1093/bjaed/mkw059)

Copyright © 2017 The Author(s) Terms and Conditions
MINIMAL INHIBITORY CONCENTRATION
Advantages:
 Easy to perform
 Familar and widely used
 Usually automated
 Highly reproducible (due to simplicity and automation)
 Rapid turnaround of results
MINIMAL INHIBITORY CONCENTRATION
Disadvantages
 MIC can vary greatly with minor variations in methodology can result in large
variations of the MIC.
 e.g. prolonged incubation may increase the apparent MIC
 e.g. smaller inoculum concentrations may decrease the apparent MIC
 e.g. MIC may change with freezer storage of samples
 Comparisons between laboratories are hindered by differences in techniques used
 Inhibition of visible growth does not mean the organisms were killed (cf. minimum
bactericidal concentration)
 MIC is not truly a single number, but a range depending on the dilution series used
during its determination
MINIMAL INHIBITORY CONCENTRATION
Disadvantages (Cont.)
 MIC does not necessarily equate with in vivo efficacy, for example:
 an antibiotic will be ineffective if it does not penetrate the affected tissues
 antibiotics with high MICs may still be effective if concentrated at the site of
infection (e.g. treatment of UTI with gentamicin, which concentrates in the urine)
 antibiotic kill characteristics are important (e.g. concentration versus time dependent
killing)
 critically ill patients may have altered pharmacodynamics and pharmacokinetics
 ‘breakpoints’ are often subjective and may not correlate with clinical outcomes
ANTIMICROBIAL THERAPY DE-ESCALATION
HAP/VAP
 Serial clinical and microbiological evaluations are necessary to re-assess therapy after
48-72 hours and to stop if infection is unlikely
 Antibiotics should be withdrawn when the following 3 criteria are fulfilled on Day 3
 A) The clinical diagnosis of pneumonia is unlikely:
 No definite infiltrates seen on repeat Chest Xray,
 And only one of the following 3 findings is present:
 Temp >38.3’C
 Leucocytosis (>12000/mm3), or Leucopenia (<4000/m3)
 Purulent tracheobronchial secretions – or an alternative non-infectious
diagnosis is confirmed
ANTIMICROBIAL THERAPY DE-ESCALATION
HAP/VAP
 Antibiotics should be withdrawn when the following 3 criteria are fulfilled on Day 3
(Cont.)
 B) Non-significant tracheobronchial aspirate culture results
 C) No severe sepsis or shock
ANTIMICROBIAL THERAPY DE-ESCALATION
 Therapy can be de-escalated for many ICU patients once respiratory tract, blood or
other specimen culture results become available, if no resistant organism (P.
aeruginosa, Acinetobacter spp, MRSA) is recovered or isolated
 Because the isolated pathogen is sensitive to a narrower spectrum antibiotic than
prescribed empirically
 Fluoroquinolones have been associated with emergence of resistant strains
 Their in-ICU use should probably be discouraged
 Antifungals should never be prescribed for Candida isolated from respiratory secretions
alone
ANTIMICROBIAL THERAPY DE-ESCALATION
 2 most commonly cited reasons to prescribe combined antibiotics for the entire
treatment duration are
 To achieve synergy
 To prevent the emergence of resistant strains
 However, antibiotic synergy has been shown to be valuable only in vitro and in patients
with neutropenia, bacteremia or a greater than 25% probability of death.
 Most patients therapy can be safely switched to monotherapy after 3 to 5 days,
provided:
 The initial therapy was appropriate
 Clinical course evolved favorably
 Microbiological data did not indicate difficult to treat microorganisms
SHORTENING TREATMENT DURATION
 Clinicians remain reluctant to prescribe fewer days of antibiotics for patients with
severe HAIs and prefer tailoring antibiotic duration to the ensuing clinical course or
using or using serial biomarker (PCT), or both
 Most patients who had CAIs or HAIs, including VAP and who received appropriate
antimicrobial therapy had good clinical reponses within the first 6 days
 Prolonged therapy facilitates colonization with antibiotic resistant bacteria

 Adapting treatment duration to PCT kinetics seems reasonable and was demonstrated to
be useful in several randomized trials, the largest of which was the PRORATA trial
PROCALCITONIN
 Procalcitonin is the propeptide of calcitonin, a 116-peptide molecule with a molecular
weight of 13 kDa
 Procalcitonin has been studied as a sepsis biomarker, to help with diagnosing/ ruling
out sepsis and to guide the initiation and cessation of antibiotics

PATHOPHYSIOLOGY
 Production:
 Produced by the C-cells of the thyroid gland and released in low concentrations in
health (plasma concentration <0.1 ng/mL)
 In sepsis is has extrathyroidal origin from inflamed/infected tissue, mostly
neuroendocrine cells in the lungs and intestine
 Synthesis is triggered by bacterial endotoxin and inflammatory cytokines
 Levels rise significantly during severe infection or inflammation (particularly in
bacterial origin)
PROCALCITONIN
PATHOPHYSIOLOGY (Cont.)
 Kinetics
 lag time of 2 to 4 h after the onset of sepsis
 peaks at 24-48 h of sepsis
 Cleared by the parathyroid gland; renal clearance is low
 Correlates with extent and severity of bacterial infection
 Circulating procalcitonin levels halve daily when the infection is controlled by the host immune
system or antibiotic therapy (less rapid fall in severe renal dysfunction)

 Biological functions of procalcitonin

 modulation of immunologic functions and vasomotility
 has time-dependent effects
 augments migratory response of monocytic cells initially, but causes inhibition after a period
of hours of incubation with PCT
 inhibits expression of inducible nitric oxide synthase (iNOS) in vascular smooth muscle cells,
but augments it in prestimulated cells
 alters expression of cytokines
 likely has different effects in patients with severe sepsis/ septic shock versus non-septic patients
PROCALCITONIN
ADVANTAGES
 Uses
 potentially useful in identifying occult bacterial infection
 potentially useful for ruling out serious bacterial infection
 Useful in discriminating between bacterial and non-infectious causes of
inflammation, as its synthesis is triggered by bacterial endotoxin
 can help guide duration of antibiotic therapy
 can help with decision to initiate antibiotic therapy in non-ICU patients
 predicts fatal outcome in CAP and critically ill septic patients (high levels correlate
with organ dysfunction; persistently high levels associated with higher mortality)
PROCALCITONIN
ADVANTAGES (Cont.)
 Others:
 strongly correlates with extent and severity of bacterial infections, better indicator of
illness severity than CRP
 Numerous trials (related to industry support) providing evidence for assisting decision
making in RTIs, pyelonephritis, bacteremia and post-operative infections
 levels peak rapidly after the first appearance of endotoxin, i.e. before blood cultures
have time to incubate
 better at differentiating SIRS from sepsis compared to CRP and other biomarkers (e.g.
IL-2, 6, 8 and TNF-alpha)
 can provide a quick result (in around 30 min), whereas blood cultures can take 24 hours
 not elevated in viral infection or autoimmune disorders
 procalcitonin production is not decreased by steroids (up to 30mg prednisolone)
 compared to CRP: more rapid rise and fall, more specific and sensitive for bacterial
sepsis, better correlation with severity
PROCALCITONIN
DISADVANTAGES
 more expensive and less available than other commonly used biomarkers (e.g. CRP)
 can increase in non-septic SIRS conditions characterised by massive cell death (e.g. after
trauma or surgery)
 not useful for identifying local infection/collections without a systemic response (may be
normal in endocarditis)
 not useful for identifying viral infection or fungal infection
 does not identify source of infection
 may not elevate in the immunocompromised
 uncertain role in pancreatitis and intra-abdominal infections
 different studies used different cut-offs (disagreement as to appropriate negative cut-off
point)
 uncertain cost-effectiveness
 Requires serial measurements (more expense)
PROCALCITONIN
DISADVANTAGES (Cont.)
 Non-infective causes of elevation include:
 Burns
 Massive tissue necrosis
 Rhabdomyolysis
 Tumour lysis
 Cardiac or major abdominal surgery
 Multi-organ system failure
 Cardiogenic shock
 Severe liver and renal dysfunction
 Treatment with T-cell antibodies
 Paraneoplastic production, eg. by medullary thyroid carcinoma or by small-cell lung
cancer
PROCALCITONIN
EVIDENCE
 Meta-analysis data is conflicting; some studies suggest procalcitonin is superior to CRP
while others have concluded it is a weak biomarker in critical illness
 A few prospective RCTs (e.g. PRORATA and studies of outpatient management of
respiratory tract infections) have shown a decrease in prescription and cost of antibiotic
therapy with no change in outcome.
PROCALCITONIN
PRORATA STUDY, 2010
 MC-RCT of 8 ICUs, n = 621 patients
 procalcitonin used to determine cessation of antibiotics therapy
 Outcomes:
 no significant difference in outcomes (mortality at 28 days)
 BUT significant reduction in antibiotic use: 6.1 vs. 9.9 days (P<0.0001)
 Commentary and criticisms:
 only 10% were surgical ICU patients
 53% of patients randomized to procalcitonin arm did not follow the algorithm-guided
treatment
 The analysis used a 10% margin of non-inferiority threshold for mortality. If a 5% margin
of non-inferiority for mortality had been used instead, the procalcitonin arm would have
had inferior mortality at 60 days
 cost-effectiveness not assessed
PROCALCITONIN

PRORATA STUDY, 2010

Duration of antibiotic treatment of the first episode in the PRORATA trial,
according to infection site. White bars indicate patients included in the control
group. Hatched bars indicate patients included in the procalcitonin-guided
group. CAP, community-acquired pneumonia; PRORATA, Use of Procalcitonin
to Reduce Patients’ Exposure to Antibiotics in Intensive Care Units; UTI,
urinary tract infection; VAP, ventilator-associated pneumonia.
PROCALCITONIN
Hoeboer et al, 2015; systematic review and meta-analysis:
 58 of 1567 eligible studies were included providing a total of 16 514 patients; of whom
3420 had bacteraemia
 optimal and most widely used procalcitonin cut-off value was 0.5 ng/mL
 overall sensitivity of 76% and specificity of 69%
 least useful in immunocompromised/neutropenic patients and best in ICU patients;
with sensitivities ranging from 66 to 89% and specificities from 55 to 78%
 Conclusions: low procalcitonin levels can be used to rule out the presence of
bacteraemia; further research is needed on the safety and efficacy of procalcitonin as a
single diagnostic tool to avoid taking blood cultures
PROCALCITONIN
SUGGESTED APPROACH (based on Meissner, 2014)
 threshold to exclude sepsis: plasma concentration of ≤0.2 ng/mL (high negative predictive value)
 threshold to diagnose sepsis: plasma concentration of ≥0.5 ng/mL
 check procalcitonin daily in patients with suspected sepsis
 patients with a strong clinical suspicion of sepsis should still be treated as such even if
procalcitonin is not initially elevated; serial levels and clinical assessment should be performed
over the next few days to determine if antibiotics should be ongoing
 as a rule of thumb, a daily drop of >30% in procalcitonin level suggests resolving inflammation
 consider changing antibiotics if the procalcitonin level is≥0.5 ng/mL and not falling
 consider continuing antibiotics if the procalcitonin level is ≥0.5 ng/mL or has fallen by <80%
from peak level
 consider stopping antibiotics if the procalcitonin level is ≤0.5 ng/mL or has fallen by >80%
from peak level
 do not use procalcitonin to guide antibiotic therapy in severe local infections that require
antibiotics (e.g. endocarditis, osteomyelitis) or patients unlikely to mount a procalcitonin response
(e.g. neutropenia, immunosuppression)
 use procalcitonin as part of an antibiotic stewardship programme
ADVERSE EFFECTS OF ANTIBIOTIC USAGE
Penicillins
 Hypersensitivity reactions
 I – Anaphylaxis
 III – Serum sickness reaction: rash, joint pain, fever
 Leucopenia
 Platelet dysfunction (Tazosin)
 Rare: direct toxicity
 Rare: cholestatic jaundice (Flucloxacillin, Augmentin)
 Mental disturbances and convulsions
ADVERSE EFFECTS OF ANTIBIOTIC USAGE

Cephalosporins Carbapenams
 GI distrurbances  GI disturbances
 Rash, Oedema  CNS: confusion,
 Thrush insomnia
 Steven-Johnson  Liver impairment
Syndrome  Seizures, esp if there
 Hemolytic Anemia are pre-existing CNS
 Thrombocytopenia and ailments
bleeding
ADVERSE EFFECTS OF ANTIBIOTIC USAGE
Glycopeptides
 Rash, itching, chills, fever
 Ototoxicity
 Nephrotoxicity
 Rare:
 Red man syndrome (caused by too rapid infusion of vancomycin)
 Leads to widespread histamine release
 Chills, fever
 Tachycardia
 Pruritus with red rash over whole body
ADVERSE EFFECTS OF ANTIBIOTIC USAGE
Macrolides
 Azithromycin
 GI, dizziness, headache
 Rare: interstitial nephritis
 Clarithromycin
 Anorexia, GI, Severe Anemia, abnormal taste
 Rare: C diff, liver failure, thrombocytopenia
 Erythromycin
 GI – reduces GI transit time via action on motilin receptors
 Vaginal thrush
 Rare: hearing loss, pancreatitis, liver failure
 Rapid IV dose can cause vent arrythmias
ADVERSE EFFECTS OF ANTIBIOTIC USAGE
Aminoglycosides
 GI effects
 Tinnitus and ototoxicity (cochlear and vestibular)
 Irreversible damage to sensory cells in cochlea and vestibular organ
 Nephrotoxic
 Tubular damage
 Reversible if medication stopped, more likely in pre-existing renal disease
 Optic nerve dysfunction (Streptomycin)
 NMJ blockade
 Very rare by itself
 With concurrent NDNMB – caused by inhibition of Ca uptake which is required for
exocytotic release of Ach
ADVERSE EFFECTS OF ANTIBIOTIC USAGE
Fluroquinolones
 Cartilage damage (<18 years old)
 GI effects
 Photosensitivity
 Dizziness and drowsiness
 Rare:
 CNS stimulation – psychosis, confusion, hallucinations, tremors
 Steven Johnson Syndrome
 Face/Neck swelling
 SOB
 Interstitial nephritis
 Tendon rupture (higher risk if on concomitant steroids or >60 yo)
ADVERSE EFFECTS OF ANTIBIOTIC USAGE
Clindamycin (Lincosamides) Sulphonamides
 GI distress – pain, diarrhoea,  Nausea and vomiting
vomiting  Headaches
 Candidiasis  Hepatitis
 Neutropenia  Hypersensitivity reactions
 Thrombocytopenia  Bone marrow suppresion
 Pseudomembranous colitis and C  Megaloblastic anemia – folate
diff deficiency
 Most limiting factor in use
 Rashes
 Rare: Methaemoglobinemia
ADVERSE EFFECTS OF ANTIBIOTIC USAGE
Antibiotic Resistance
 Lack of novel antibiotic development
 Infectious Disease Society of America (ISDA) has kick started a global initiative
with aims to develop 10 new antibacterial drugs by 2020
 In critical care:
 Majority of infections are a result of a small group of bacteria, which are becoming
increasingly antibiotic resistant.
 ESCAPE
 ADVERSE EFFECTS OF ANTIBIOTIC USAGE
Antibiotic Resistance
 ESCAPE acronym for increasingly resistant bacteria

E Enterococcus faecium (vancomycin resistance—VRE)

S Staphylococcus aureus (methicillin resistance—MRSA, vancomycin intermediate
resistance—VISA, vancomycin resistance—VRSA). S. pneumoniae (penicillin
resistance)
C Clostridium difficile
A Acinetobacter baumannii (carbapenem, cephalosporin, aminoglycoside and
quinolone resistance)
P Pseudomonas aeruginosa (carbapenem resistance)
E Enterobacteriaceae (which encompasses K. pneumoniae, Enterobacter species and
E. coli—3rd generation cephalosporin and carbapenem resistance)
 CLOSTRIDIUM DIFFICLE
Overview
 Clostridium difficile enterocolitis and pseudomembranous colitis (PMC)
 Acute inflammatory disease of colon commonly associated with antibiotic use
Pathophysiology
 Mechanism
 antibiotic exposure -> overgrowth of C. difficile -> increased toxin production -> mucosal damage ->
inflammation and necrosis
 rarely other organisms have been implicated: Staph aureus, Salmonella, Clostridium perfringens, Yersinia,
Shigella, Campylobacter, CMV, Entamoeba, Listeria
 Complications related to diarrhoea
 Hypovolaemia
 Electrolyte disturbance: hypokalaemia, hypomagnesaemia
 Complications related to intestinal infection
 Sepsis and septic shock
 Perforation
 Toxic megacolon
 Bleeding
 CLOSTRIDIUM DIFFICLE
Clinical features:
 diarrhoea 3-9 days post initiation of antibiotics
 may start weeks after discontinuation of antibiotics
 loose stools -> toxic megacolon and colonic perforation
 profuse, watery/mucoid, foul-smelling stool
 may contain blood and pseudomembranes
 Fever
 rarely: oligoarthritis and iridocyclitis
CLOSTRIDIUM DIFFICLE
Risk factors:
 Antibiotic exposure – any antimicrobial can incite disease
 Likely – beta-lactams, clindamycin
 Uncommon – quinolones, imipenem, metronidazole
 Rare – vancomycin, erythromycin, tetracycline, gentamicin
 Other
 age >65yo
 previous GI surgery
 renal impairment
 prolonged hospitalisation
 gastric acid suppression
 renal failure
 immunocompromised and chemotherapy patients
CONCLUSIONS
 Antibiotic therapy for ICU patients with infections should be viewed as a 2 stage
process:
 First involves administering broad-spectrum antibiotics to avoid inappropriate
treatment of true bacterial infections
 Second focuses on trying to achieve the first without antibiotic overuse or abuse
 Any antibiotic stewardship program should be implemented in a structured manner and
requires an inter-disciplinary team