Antibiotik Pada Pasien Sakit Kritis

Adhrie Sugiarto
FKUI / RSUPN Cipto Mangunkusumo
Jakarta 2014
Pendahuluan
• Pemberian antibiotik dini dan tepat merupakan penentu keberhasilan
tatalaksana pasien sakit kritis dengan sepsis
• Terapi antibiotik yang diberikan harus tepat dalam hal :
• Waktu (Kapan memulai, Durasi)
• Cakupan (Jenis, Kombinasi)
• Dosis (Loading dose, Maintenance dose)
SSC Recommendation on Antimicrobial
Therapy
• 1. Administration of effective intravenous antimicrobials within the first hour of
recognition of septic shock (grade 1B) and severe sepsis without septic shock (grade 1C)
as the goal of therapy.
• 2a. Initial empiric anti-infective therapy of one or more drugs that have activity against
all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate
concentrations into tissues presumed to be the source of sepsis (grade 1B).
• 2b. Antimicrobial regimen should be reassessed daily for potential deescalation (grade
1B).
• 3. Use of low procalcitonin levels or similar biomarkers to assist the clinician in the
discontinuation of empiric antibiotics in patients who initially appeared septic, but have
no subsequent evidence of infection (grade 2C).
• 4a. Combination empirical therapy for neutropenic patients with severe sepsis (grade 2B)
and for patients with difficult-to-treat, multidrugresistant bacterial pathogens such as
Acinetobacter and Pseudomonas spp. (grade 2B).
SSC Recommendation on Antimicrobial
Therapy
• 4b. Empiric combination therapy should not be administered for more than
3–5 days. De-escalation to the most appropriate single therapy should be
performed as soon as the susceptibility profile is known (grade 2B).
• 5. Duration of therapy typically 7–10 days; longer courses may be
appropriate in patients who have a slow clinical response, undrainable foci
of infection, bacteremia with S. aureus; some fungal and viral infections or
immunologic deficiencies, including neutropenia (grade 2C).
• 6. Antiviral therapy initiated as early as possible in patients with severe
sepsis or septic shock of viral origin (grade 2C).
• 7. Antimicrobial agents should not be used in patients with severe
inflammatory states determined to be of noninfectious cause (UG).
Pea F, Viale P: The antimicrobial therapy puzzle: could pharmacokinetic- pharmacodynamic
relationships be helpful in addressing the issue of appropriate pneumonia treatment in critically ill
patients? Clin Infect Dis 2006, 42:1764-1771
McKinnon PS, David SL. Pharmacokinetic and Pharmacodynamic Issues in the Treatment of
Bacterial Infectious Diseases. Eur J Clin Microbiol Infect Dis (2004) 23: 271–288
Waktu pemberian antibiotik

Keterlambatan/ketidaktepatan
terapi antibiotik menjadi
masalah serius

7
Duration of hypotension prior to effective antimicrobial
therapy: impact on survival in septic shock

100

80
Mortailty (%)

60

40

20

0
0–30′ 30′–1h 1–2 2–3 3–4 4–5 5–6 6–9 9–12 12–24 24–36 >36
Time of first dose of antibiotics after
the onset of shock (hours)
Kumar et al. Crit Care Med 2006;34:1589–1596
8
Get it right first time!
Appropriate Inappropriate
100 antibiotic treatment antibiotic treatment
90 *

80
*
Mortality rate (%) 70 * p<0.05
60
50
*
40 *

30
20
10
0
Micek Harbarth Garnacho Dhainaut
(n=102) (n=904) (n=406) (n=1690)

Micek et al. Pharmacotherapy 2005;25:26–34

9
Duration of antibiotic therapy
8 vs 15 days of antibiotic therapy for VAP
—Prospective, randomised, multicentre trial
—Compare outcomes of therapy with ‘short’
(8-day) versus ‘long’ (15-day) courses of antibiotics
– Patients with microbiologically proven VAP
(bronchoscopic bronchoalveolar lavage protected specimen brush
or Combicath)
– Receiving appropriate initial empiric treatment
– Double-blind until Day 8
—Major endpoints (Day 28)
– Mortality
– Recurrence of pulmonary infection
– Antibiotic use
10 Chastre et al. JAMA 2003;290:2588–2598
Pemberian antibiotik yang lama
dapat menyebabkan timbulnya
resistensi
!!!

11
Cakupan Antibiotik

Pola Kuman
Pembiayaan
Guidelines

Hasil kultur
So how do you get it right?

Regional variations in resistance

—Know your local organisms and their sensitivities
– This will largely determine your antibiotic choices

15
Antibiotic susceptibility of Klebsiella pneumoniae,
Enterobacter cloacae and Pseudomonas aeruginosa from Spain and Turkey (MYSTIC
data 2006)

Meropenem Piperacillin–tazobactam Ciprofloxacin

% Susceptibility (CLSI criteria) 100

90
80
70
60
50
40
30
20
10
0
K. pneumoniae E. cloacae P. aeruginosa
(Spain) (Turkey) (Spain) (Turkey) (Spain) (Turkey)
Organisms (country)
16
How do I de-escalate
 Definition of De-escalation
—De-escalation involves the practice of:
– Starting with a broad-spectrum empiric therapy
regimen designed to avoid inappropriate therapy,
combined with a commitment to:
1.Change from broad- to narrow-spectrum therapy
2.Reduce the duration of therapy
3.Stop therapy in selected patients, as dictated by the
patient’s clinical response and by culture results
—Culture data are used to narrow, focus or even stop
therapy

18
Why de-escalate therapy?
—The vicious cycle created by the need for aggressive, broad-spectrum
antibiotic therapy to achieve appropriate therapy, which creates
more resistance and more overuse of antibiotics, can only be broken
by
– De-escalation

19
 Strategi dan pendekatan diagnostik

Dugaan HAP, VAP atau HCAP

Ambil kultur dan pemeriksaan mikroskopik sekret saluran napas bawah

Bila secara klinis tidak curiga pneumonia dan hasil mikroskopi sekret saluran napas bawah negatif,
terapi antimikrobial empirik dimulai dengan menggunakan algoritme Gb.2 dan data mikrobiologi lokal

Hari ke 2 dan 3 : cek hasil kultur dan keadaan klinis (temperatur, leukosit, foto rontgen dada, oksigenasi,
sputum, perubahan hemodinamik dan fungsi organ)

Perbaikan klinis dalam 48 sampai 72 jam

Tidak Ya
Kultur – Kultur + Kultur – Kultur +

Sesuaikan jenis antibiotika, Pertimbangkan De-eskalasi antibiotika,

Cari infeksi dan penyulitnya obati pasien selama 7-8
dan cari kuman lain dan penghentian
di tempat lain. komplikasinya hari dan evaluasi
antibiotika
Dosis Antibiotik Pada Pasien Sakit Kritis
Surviving Sepsis Campaign 2012 :
ANTIBIOTIC DOSING IN CRITICAL ILL

The issue of dosing is of particular relevance in patients with

severe sepsis or septic shock, in whom various
pathophysiological conditions may significantly alter the
pharmacokinetic behaviour of drugs
Importantly, pharmacokinetic studies to define drug dosages for
regulatory purposes are usually carried out in healthy
volunteers, who by definition are not patients.
Consequently, it is not surprising that dosing regimens of several
antimicrobials are expected to be significantly different in ICU
patients from those suggested for clinically stable patients
ANTIBIOTIC DOSING IN CRITICAL ILL

AKI + RRT

Altered Cl
Increased Vd
AKI

?
Plasma
Concentration

Roberts JA, Lipman J. Pharmacokinetic issues for antibiotics in

the critically ill patient. Crit Care Med 2009; 37: 840–851
Kesimpulan
• Penggunaan antibiotik pada sakit kritis :
• Prompt
• Appropriate
• Adequate
• Penentuan dosis antibiotik pada pasien sakit kritis perlu
mempertimbangkan kondisi patofisiologis yang mempengaruhi
farmakokinetik dari antibiotik
• Penggunaan antibiotik dengan tepat dapat mencegah timbulnya kegagalan
terapi dan resistensi terhadap antibiotik
• TDM sangat dianjurkan apabila memungkinkan
• Dosis yang diberikan disesuaikan dengan kondisi terakhir dari pasien