a summary of guide to antibiotic choice in hospital critical care set up

1. ANTIBIOTIC CHOICES IN ICU
Dr. Okiko Andrew- Clinical Pharmacist-
Internal med/infectious Disease

2. Introduction
Epidemiological data perspective.
Different ICU profiles
Microbiological data
Principles of antibiotic use
Choice of antibiotics
Antimicrobial resistance & its prevention
Conclusions

3. Introduction
Infections are important cause of morbidity
& mortality in critically ill patients
Type of infection varies according to type
of ICU
Different organisms in different ICU’s
Geographical variation
Increasing resistance to antimicrobials

4. Different infections in Critically sick/
ICU Patients
Bloodstream infections- catheter related
Pneumonias
Gastrointestinal infections
CNS infections
Urinary Tract infections
Skin & Soft Tissue infection
[Crit Care Med, 2004,32, 1510-1526]

5. Results of EPIC Study
34.4
30.1 28.7
19.1
17.1
0
5
10
15
20
25
30
35
Percentage
Enterobacteriaceae
S.aureus
P.aeruginosa
CoNS
Fungi

6. Risk factors for ICU acquired
infections-
Increasing length of ICU stay (>48 hrs)
– Mechanical ventilation
– Diagnosis of trauma
– Central venous catheterization
– Pulmonary artery catheterization
– Urinary tract catheterization
– Stress ulcer prophylaxis

7. Pediatric ICU
• Post operative patients
• Septicemia
• Respiratory tract
infections
• Neurological illnesses
• Others e.g.renal,
gastrointestinal etc

8. Ventilator Associated Pneumonia
(VAP) Pathogens
1. Staph. aureus
2. Pseudomonas aeruginosa
3. Enterobacter spp.
Am J Infect Control 1999, 27, 520-32

9. Urinary Tract Infection (UTI) Pathogens
1. E. coli
2. Candida albicans
3. Enterococcus
[Am J Infect Control 1999, 27, 520-32]

10. Blood Stream Infection (BSI)-
Pathogens
1.Coagulase negative
staphylococci
2.Enterococcus
3.Staphylococcus aureus
[Am J Infect Control 1999, 27, 520-32]

11. Common Pathogens
• Gram negative-
– Acinetobacter spp.
– Pseudomonas spp.
– Klebsiella pneumoniae
– E.coli
– Enterobacter spp.
• Gram positive –
– Staphylococcus aureus
– Coagulase negative
staphylococci (CoNS)
– Enterococcus spp.
– Streptococcus
(Source: Deptt. of Microbiology,AIIMS)

12. Principles of Antibiotic Use
Goal – To choose a drug selectively active
against the most likely infecting organism
& least potential to cause toxicity
Empirical / Definitive /
Prophylactic

13. Choice of Antibiotic in ICU
Community acquired pneumonia
Ventilator associated pneumonia
Intravascular catheter related
infection
Urinary tract infection
Intra abdominal infection
Central nervous system infection

14. Community Acquired Pneumonia
(CAP)
Severe CAP - Etiology
Organisms-
–S.pneumoniae
–Atypical pathogens (Chlamydia pneumoniae,
M.pneumoniae, Legionella)
–Enteric gram negatives
–H.influenzae
– Staph.aureus } specific risk
– Pseudomonas aeruginosa } factors
– Respiratory tract viruses

15. Treatment
Patients with no risk factors for pseudomonas-
–Intravenous β- lactam (Co Amoxyclav or ceftriaxone)
plus either
–Intravenous macrolide (azithromycin)
or
Intravenous fluoroquinolone
[Am J Respir Crit Care Med 2001, 163,1730-54]

16. Treatment
Patients with risk factors for
pseudomonas-
– Selected I.V. antipseudomonal β- lactam
(cefepime, imipenem, meropenem, piperacillin/tazobactam)
plus I.V.antipseudomonal quinolone
(ciprofloxacin,Levofloxacin)
OR
– Selected I.V. antipseudomonal β- lactam plus
I.V. Aminoglycoside Plus either
I.V. macrolide (Azithromycin)
or I.V. fluoroquinolone

17. Treatment
If patient is allergic to β- lactam, it should be
replaced with caftazidime and combined
with aminoglycoside & antipseudomonal FQ
The β- lactam used should be active against
DRSP
Agents active against pseudomonas are not
recommended as primary therapy when this
organism is not suspected

18. Duration Of Treatment
Factors-
– Coexisting illness and/or bacteremia
– Severity of illness at onset of antibiotic therapy
– Subsequent hospital course
In general-
– S.pneumoniae – 7-10 d
– Myco.pneumoniae – 10-14 d
– Chlamydia pneumoniae – 10-14 d
– Legionella – 10-14 d
[Am J Respir Crit Care Med 2001, 163,1730-54]

19. Switch to Oral Therapy
Criteria –
–Improvement in cough & dyspnea
–Afebrile (<100 °F ) on two occasions 8 h apart
–White cell count decreasing
–Functioning G.I. tract with adequate oral intake
Narrowest spectrum agent according to etiologic
organism with an appropriate pharmacokinetic
profile should be chosen
Compliance is very important

20. Ventilator Associated Pneumonia In ICU

21. VAP in ICU
A pneumonia is considered to be ventilator
associated when it occurs after intubation & is
judged not to have incubated before an artificial
airway is put in place
Incidence = 9-68 %
Mortality = 33-71 %
(Am Rev Respir Dis 2009142,523-528)

22. Risk factors for development of VAP
• Shock
• Multiorgan failure
• Worsening respiratory failure
• Ultimately or rapidly fatal underlying illness
• Age > 60 years
• Supine position
• Inappropriate or prior antibiotic treatment
[Chest Surg Clin N Am 2002, 379-395]

23. Microbiology of VAP
• Gram negative bacilli (GNB) and staphylococcus
aureus are the most common causes of VAP
• Among GNB, Pseudomonas aeruginosa and
Acinetobacter baumani are most frequent isolates.
• The role of anaerobes has not been thoroughly
investigated
[CDC NNIS System; Am J Infect Control 1999,27, 520-532]

24. VAP-Empiric or Directed Treatment
Empiric treatment is reasonable
No role of prophylactic antibiotics
Non availability of accurate, cost effective and
rapid diagnostic procedures
Choice of therapy should be based on
–Knowledge of most frequent pathogen and their
pattern of susceptibility
–Specific risk factors esp. prior antibiotic use
–Time since admission to hospital
–Duration of MV before development of VAP

25. VAP-Monotherapy or Combination
Therapy
55 % of VAP are polymicrobial in nature
Combination therapy is preferable
Reduces appearance of resistance
Synergistic effects of antibiotics
Decreases risk of inadequate treatment before
microbiological data are available
(AJRCCM 1998,157,531-9)

26. VAP-Antibiotic Regimen
Early onset VAP & without risk factors-
First choice-
Second or third generation nonpseudomonal
cephalosporins or combined β -lactam/ β -lactamase
inhibitor
If patient is allergic to these-
Fluoroquinolones or clindamycin + ceftazidime

27. VAP-Antibiotic Regimen
• Any onset VAP & with risk factors-
First choice-
– Aminoglycosides or Levofloxacin /ciprofloxacin
plus one of the following:
– Antipseudomonal penicillin
– β-lactam/β-lactamase inhibitor
– Ceftazidime or Cefoperazone
– Imipenem
– Azteonam ± Vancomycin
(AJRCCM 153,1995,1711-25)

28. VAP-Antibiotic Regimen
Patients at risk of aspiration pneumonia should
receive antibiotics with anaerobic activity
A glycopeptide may be added if the prevalence
of MRSA is high & especially if β-lactams
have been given previously

29. VAP-Modification of Initial
Regimen
Adjust therapy after availability of
microbiological data.
Aim – narrower spectrum antibiotics
Therapeutic de-escalation advisable
Modify if appearance of resistant
organisms
Poor clinical response

30. VAP-Duration of Treatment
• There must be clinical improvement & afebrile period of at
least 48 hrs. before stopping antibiotics
• P.aeruginosa or A.baumani infections should be treated for
minimum of 14-21 days
• Patients with multilobar involvement, malnutrition, severe
debilitation, cavitation, or a necrotizing GNB pneumonia
also require 14-21 days treatment
(AJRCCM 1995,153,1711-25)

31. Prevention of VAP – Physical Strategies
• Oral endotracheal tube Recommended
• Ventilator circuit change Recommended
• Heat & moisture exchanger Recommended
• Weekly change of humidifier Recommended
• Closed suction system Recommended
• Change in suction system Recommended
• Drainage of subglottic secretions Consider
• Systematic search for sinusitis No recommendation
• Chest physiotherapy No recommendation
• Early tracheostomy No recommendation
(Ann Intern Med 2004;141:305-313)

32. IVC Related Infections in ICU
Major cause of morbidity & mortality in critically
ill patients
Organisms-
– Coagulase negative staphylococci
– Staph. Aureus
– Aerobic gram negative bacilli
– Candida albicans
(IDSA Guidelines; Clin Infect Dis 2001;32,1249-72)

33. Treatment
Vancomycin – where methicillin resistant
staphylococci (MRSA) is common
Flucloxacillin– where MRSA or MRSE are rare
Linezolid – if pt. is allergic to vancomycin
3rd or 4th Gen. cephalosporin added – in
immunocompromised or severely ill pts.
Amphotericin – if possibility of fungemia
[Clin Chest Med 24(2003) 645-669]

34. Duration of Treatment
Uncomplicated infections – 10-14 d
BSI due to CoNS – 5-7 d (if IVC removed)
10-14 d (if IVC not removed)
BSI due to Candida – 14 d after last positive
culture
[Clin Chest Med 24(2003) 645-669]

35. Complicated Intra-abdominal infections
Infections that extend beyond the hollow viscus of
origin into the peritoneal space & associated
either with abscess formation or peritonitis
Can be –
– Community acquired
– Hospital acquired
(Clin Infect Dis 2003;37, 997-1005)

36. Pathogens
• Hospital acquired:
– P.aeruginosa
– Enterobacter spp.
– Proteus spp.
– MRSA
– Enterococci
– Candida spp.
• Community acquired:
– Gram neagtive aerobes &
facultative organisms e.g.
E.coli
– Anaerobes e.g. B.fragilis
– Streptococci
– Enterococci

37. Treatment-Community Acquired Infection
• MILD-MODERATE
– Single agent –
• Coamxyclav-
Ampicillin/sulbactam
• Ertapenem-costly
– Combination –
• Cefazolin/ cefuroxime plus
Metronidazole
• Cipro /levo/ gati/
moxifloxacin with
Metronidazole
• SEVERE INFECTIONS-
– Single agent-
• Piperacillin/tazobactam
• Imipenem/ cilastatin
• Meropenem
– Combination –
• 3rd / 4th gen. cephalosporin plus
Metronidazole
• Ciprofloxacin plus
Metronidazole
• Aztreonam/ceftazidime plus
Metronidazole

38. Treatment- Hospital Acquired Infection
Complex multidrug regimens (e.g. an
aminoglycoside/ quinolone/ carbapenem &
vancomycin) is recommended
Treat according to local nosocomial
resistance patterns
Modify treatment according to results of
microbiological data

39. Nosocomial UTI
• Risk Factors-
– Presence of indwelling urinary catheter- M. Imp.
– Female gender
– Extended ICU stay
Complications – Urosepsis
– Age >60 years
– Extended hospital stay
– Extended duration of urinary catheterization
(Infection 1999; 27(1); 16-22)

40. Nosocomial UTI -Etiology
E.coli
Candida albicans
P aeruginosa
Enterococcus spp.
Klebsiella
pneumoniae
(Clin Chest Med 2003; 24,645-69)

41. Nosocomial UTI- Treatment
Piperacillin/tazobactam or ticarcillin/clavulanate
Imipenem / Meropenem
Ciprofloxacin / Levofloxacin / Gatifloxacin
Ampicillin with Gentamicin
Ceftazidime with Vancomycin
Antifungal therapy if strong clinical suspicion of
disseminated candidiasis & pt. is unstable
(Clin Chest Med 2003; 24,645-69)

42. CNS Infections in ICU
Pyogenic Meningitis
Organisms
• Hospital acquired:
– Staphylococci
– Gram negatives
including P.aeruginosa
• Community acquired:
– S. pneumoniae
– N. meningitidis
– Gr. B streptococci
– L. monocytogenes
HPIM 16th Ed.

43. Treatment of Pyogenic Meningitis
Community acquired –
– Cefotaxime / Ceftriaxone + Vancomycin
Hospital acquired –
– 3rd gen cephalosporin/ Ceftazidime +
Vancomycin

44. Summary
Optimize antimicrobial effectiveness –
–Avoid inadequate treatment
–Good oral hygiene practice.
–Combination antimicrobial treatment
–Antibiotic cycling & scheduled antibiotic changes
–Area specific empirical antimicrobial therapy
–Limit short course antibiotic prophylaxis to clinically
validated indications
–Avoid routine antimicrobial decontamination of
digestive tract in ICU