Fighting Difficult Pathogens Resistance

in HAP/VAP. What Should We Do?

Rezki Tantular
Pendahuluan
• Antibiotika dikembangkan untuk menangani berbagai penyakit
infeksi bakteri
• Tujuannya: menurunkan morbiditas dan mortalitas akibat
penyakit infeksi
• Ada hubungan langsung antara penggunaan antibiotika dengan
peningkatan kejadian resistensi antibiotika
→ masalah global
Antibiotika
• Ideal: antibiotika sesuai hasil uji resistensi → lama , sehingga
→ terapi empirik
• Empirik → mencakup 90% patogen penyebab → butuh pola
resistensi setempat
• De-eskalasi setelah ada hasil kultur dan perbaikan klinis
• Kombinasi AB → kecurigaan MDR
• Jangan ganti AB bila <72 jam, kecuali perburukan klinis
Pendahuluan
• Pneumonia merupakan penyakit infeksi dengan tingkat
mortalitas yang tinggi di dunia

Sumber: Global Burden of Disease Study, IHME, 2018

 Definisi

HAP VAP
zv zv
Hospital-acquired Ventilator-associated
Pneumonia1-3 Pneumonia1-3

Pneumonia yang terjadi > 48 jam

setelah masuk rumah sakit, Pneumonia yang terjadi > 48 jam
Ventilator-associated
tetapi tidak dalam masa inkubasi setelah ventilasi mekanik
1-3
saat masuk
Pneumonia (VAP)

1. Kalil AC et al. Clin Infect Dis. 2016;63(5):e61–e111. 2. Cilloniz C et al. Int J Mol Sci. 2016;17(12):2120. doi:10.3390/ijms17122120. 3. FNIH. Foundation for the NIH Biomarkers Consortium HABP/VABP Project
Team, May 26, 2017. fnih.org/what-we-do/biomarkers-consortium/programs/ventilator-acquired-bacterial-pneumonia. Accessed September 4, 2019. 4. Food and Drug Administration. Guidance for industry.
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. Accessed September 23, 2019.
 Perjalanan penyakit HAP

Zaragoza R, Vidal-Cortés P, Aguilar G, Borges M, Diaz E, Ferrer R, et al. Update of the treatment of nosocomial pneumonia in the ICU. Crit Care. 2020 Dec;24(1):383.
Waters, B., & Muscedere, J. (2015). A 2015 update on ventilator-associated pneumonia: new insights on its prevention, diagnosis,
and treatment. Current infectious disease reports, 17(8), 41.
 Ketepatan Waktu Pemberian Terapi adalah Prediktor Mortalitas

Dalam sebuah decisional model framework

Mortalitas di Rumah Sakit Pasien VAP1,2

Dalam sebuah meta-analisis
Penggunaan antibiotik inisial yang
tidak tepat meningkatkan
mortalitas dan lama perawatan
pasien di ICU3*

Terapi antimikrobial diberikan <2 hari
dari indeks kultur
Tujuan Studi
• Menilai cosf-effectiveness beberapa study
Keterbatasan
• Penggunaan model hanya penyederhanaan dari
realita, membutuhkan asumsi, dan merumuskan input
dari berbagai sumber, hasil mungkin tidak
mencermikan studi tunggal
Terapi antimikrobial diberikan >2
hari dari indeks kultur

ICU, intensive care unit; VAP, ventilator-associated pneumonia.

*A meta-analysis of 57 studies assessed the consequences of appropriate vs inappropriate antibiotic therapy in the treatment of Gram-negative bacterial infections in the hospital setting.
In the majority of the studies, appropriate antibiotic therapy was defined based on susceptibility and timeliness of treatment.
1. Tsalik EL et al. Ann Am Thorac Soc. 2016;13(3):401-413. 2. Bonine NG et al. Am J Med Sci. 2019;357(2):103-110. 3. Raman G et al. BMC Infect Dis. 2015;15(395):1-11.
 Prevalensi Patogen Gram Negatif yang Dikumpulkan dari Infeksi
Saluran Napas di ICU

Pseudomonas
aeruginosa, Escherichia
coli, dan Klebsiella
pneumoniae
mencangkup hampir
59% dari semua jenis
infeksi saluran napas
yang disebabkan oleh
bakteri gram-negatif1;
20% resisten
meropenem
Deskripsi studi1: Keterbatasan2:
• Program SMART memonitor sensitivitas in vitro dari isolate bakteri dari • Jumlah peneliti SMART berbeda-
antimikroba pilihan di seluruh dunia beda tiap tahun
• Pengumpulan 17.629 isolat infeksi saluran napas pada tahun 2015-2017

RTI, respiratory tract infection; SMART, Study for Monitoring Antimicrobial Resistance Trends.
1. Global SMART Data 2017. 2. Karlowsky et al. J Med Microbiol. 2017;66:61-69.
 Patogen Resisten
• MDR:
Berdasarkan uji kepekaan → resisten terhadap
banyak antimikroba, dengan kelas atau sub klas
yang berbeda; resisten terhadap 3 atau lebih
kelas antimikroba; resistensi silang atau ko-
resisten banyak kelas antimikroba
• XDR:
Resisten terhadap hampir semua atau semua
agen antimikroba yang disetujui
• PDR:
Resisten terhadap semua antimikroba
 Patogen MDR (Multi Drug Resistant)
• Patogen MDR merupakan tantangan dalam terapi dan
tatalaksana di mana semakin hari, resistensi juga semakin
meningkat, sehingga pilihan terapi menjadi semakin terbatas
• Patogen MDR → Morbiditas dan mortalitas ↑
• Menunda terapi → semakin memperburuk outcome
• Overuse / misuse antibiotika → WHO mengingatkan tentang
resistensi antibiotika
• Antibiotika yang tepat sedini mungkin →Penting untuk
keselamatan pasien
• ESKAPE = Enterococcus faecium, Staphylococcus aureus, Klebsiela
pneumoniae, Acinobacter baumanii, Pseudomas aeruginosa, Enterobacter
species
• Pemilihan, optimasi, dan durasi terapi → individual
• Rapid diagnosis & early phenotypic and genotypic → early appropriate AB
• Patogen MDR berhubungan dengan hospital-acquired pneumonia (HAP)
dan ventilator-associated pneumonia (VAP)
– Infeksi patogen MDR, baik bakteri Gram positif dan Gram negatif
umumnya terjadi pada pasien dengan HAP atau VAP
– Strategi efektif untuk pencegahan HAP dan VAP dan antibiotika baru diperlukan
untuk memerangi patogen MDR.
 Faktor Risiko Infeksi Bakteri MDR
Faktor Risiko Infeksi Bakteri MDR
VAP
Penggunaan antibiotic IV sebelumnya dalam 90 hari terakhir
Syok sepsis saat VAP
ARDS
Telah dirawat di RS ≥ 5 hari sebelum terkena VAP
Acite renal replacement therapy sebelum awitan VAP
HAP
Penggunaan antibiotic IV sebelumnya dalam 90 hari terakhir
HAP/VAP MRSA
Penggunaan antibiotic IV sebelumnya dalam 90 hari terakhir
HAP/VAP Pseudomonas MDR
Penggunaan antibiotic IV sebelumnya dalam 90 hari terakhir

Perhimpunan Dokter Paru Indonesia. Hospital Acquired Pneumonia (HAP) dan Ventilator Acquired Pneumonia (VAP): Pedoman Diagnosis dan Penatalaksanaan di Indonesia. 2018
 Potensi Resistansi:
Tidak sama untuk setiap AB
P. aeruginosa
Anti - P. aeruginosa Resistance
Antibiotik Activity Potential
Piperacillin-tazobactam ++++ +
Ceftazidime ++++ ++++
Cefepime ++++ +
Imipenem ++++ ++++
Meropenem ++++ +
Gentamicin + ++++
Amikacin ++ +
Levofloxacin ++ +
Ciprofloxacin +++ ++++

Cunha BA. Semin Respir Infect. 2002;17:231-239.

 Faktor yang harus dipertimbangkan dalam
pemberian antibiotik
• Data mikrobiologi
• Monoterapi vs. kombinasi terapi
• Dosis obat
• Penetrasi
• Waktu
• Toksisitas
• Risiko Resistensi
• Pemakaian antibiotik sebelumnya

Kollef MH. Clin Infect Dis 2000;31(suppl 4): S131-S138 Ibrahim EH et al. Chest
2000; 118:146-155
 Penetrasi Paru Merupakan Pertimbangan yang Penting dalam
Memilih Terapi

Antibiotik harus menunjukkan penetrasi ke epithelial lining fluid (ELF) paru-paru yang baik
yang merupakan lokasi infeksi

Penetrasi ke paru
dianggap berhasil bila
terdapat nilai kritis
ELF : konsentrasi
plasma pada
pengobatan HAP/VAP

AB, antibiotic; HAP, hospital-acquired pneumonia; IV, intravenous; VAP, ventilator-associated pneumonia.
1. Välitalo PAJ et al. Pharm Res. 2016;33:856-867.
Strategi
Penatalaksanaan MDRO Pencegahan HAP
• Pencegahan dan pengendalian transmisi • Cuci tangan
MDRO • Perawatan kebersihan rongga mulut
– Cuci tangan • Pencegahan aspirasi dan disfagia
– Kewaspadaan kontak
• Positioning di atas bed
– Surveilance → Kultur permukaan
– Edukasi • Mobilisasi
– Pembersihan lingkungan yang lebih baik • Pencegahan infeksi viral
– Komunikasi
• Pemilihan antibiotika empirik yang
adekuat
• Tempatkan pasien MDRO di ruangan
tersendiri
 Antibiotik
• Adjuvan:
– Potensiator antibiotika atau “resistance breakers” merupakan
senyawa yang tidak memiliki aktivitas antimikroba namun ketika
dikombinasikan dengan antibiotika → meningkatkan efektivitas
antibiotika atau mencegah terjadinya resistensi obat tersebut,
contoh: penghambat beta laktam, penghambat pompa efluks, dsb
– Mekanisme: bermacam2, tergantung dari adjuvan nya
 Hopital-acquired Pneumonia (HAP)

Risk of mortality (-) Risk of mortality (-) Risk of mortality (+)

Risk factors of MRSA (-) Risk factors of MRSA (+) Risk factors of MRSA (+)

Piperacillin tazobactam 4.6 g IV q6 h Piperacillin tazobactam 4.6 g IV q6 h

Or
Or Cefepim 2 g IV8h
Piperacillin tazobactam 4.6 g IV q6 h
Or
Cefepim 2 g IV8h Imipenem 500 mg IV q6h
Or
Meropenem 1 g IV 8h
Or
Cefepim 2 g IV8h
Plus
Levofloxacin 750 IV daily
Or
Levofloxacin 750 IV daily
Or Ciprofloxacin 400 mgIV q8h
Levofloxacin 750 IV daily
Or
Imipenem 500 mg IV q6h Amikacin 15-20 mg/kg IV daily
Or
Gentamisin 5-7 mg/kg IV daily
Meropenem 1 g IV 8h Tobramycine 5-7 mg/kg IV daily
Imipenem 500 mg IV q6h
Plus Plus
Meropenem 1 g IV 8h
Vancomycine 15 mg/kg IV q8-12h Vancomycine 15 mg/kg IV q8-12h
Or
Or Lineezolid 600 mg IV q12h

Lineezolid 600 mg IV q12h

ATS IDSA. Management of Adults with HAP/VAP. 2016;63(5):575-82.

 Antibiotik Definitif untuk HAP/VAP
Pemilihan Antibiotik Definitif pada HAP/VAP

Jenis Mikroba Jenis Antibiotik Dosis

Methicilin Resistant S. aureus Vankomisin 15 mg/kgBB/12 jam

(MRSA) Linezolid 600 mg 2x/hari dalam 30 menit
Methicilin Sensitive S. aureus Amoksilin klavulanat 3 x 2.2 gr
(MSSA) Seftriakson 1 gr IV / hari
Sefotaksim 3 x 2 gr
Levofloksasin 750 mg IV per hari dalam 30 menit
P. aeruginosa Sefepime 2 gr IV 2-3x/hari (infus 3 jam)
Seftazidim 2 gr IV 3x/hari
Levofloksasin 750 mg IV per hari dalam 30 menit
Siprofloksasin 400 mg IV 3x/hari dalam 30 menit
Meropenem 1 gr IV 3x/hari (infus 3 jam)
Imipenem 0.5 – 1 gr IV 4x/hari (infus 2 jam)
Klebsiela pneumonia Amoksilin klavulanat 3 x 2.2 gr
Seftriakson 1 gr IV / hari
Sefotaksim 3 x 2 gr
Levofloksasin 750 mg IV per hari dalam 30 menit
Acinetobacter baumanii Ampisilin sulbactam 3 x 3 gr
Meropenem 1 gr IV 3x/hari (infus 3 jam)
Imipenem 0.5 – 1 gr IV 4x/hari (infus 2 jam)
Perhimpunan Dokter Paru Indonesia. Hospital Acquired Pneumonia (HAP) dan Ventilator
Acquired Pneumonia (VAP): Pedoman Diagnosis dan Penatalaksanaan di Indonesia. 2018
 Recommended antibiotic treatment options for difficult-to-treat (DTR)
Pseudomonas aeruginosa, assuming in vitro susceptibility to agents in table

HAP/VAP

Ceftazidime-avibactam (CZA) is a combination of the third-generation cephalosporin ceftazidime and a novel non-beta-lactam beta-lactamase inhibitor
avibactam. It is a first line therapy for dicult-to-treat infections due to Gram-negative bacilli (GNB).

the U.S. Food and Drug Administration (FDA) approved CZA in 2015 for the treatment of complicated intra-abdominal infections (cIAI), complicated
urinary tract infections (cUTI). The European Medicines Agency (EMA) approved CZA in 2016 for the treatment of adults with cUTIs, cIAIs, and hospital-
acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP).

IDSA Antimicrobial Resistant Treatment Guidance: Gram-Negative Bacterial Infections. 2020.

Antibiotics. 2020; 9: 388. doi:10.3390/antibiotics9070388.
 Ceftazidime-avibactam: clinical considerations in serious
Gram-negative bacterial infections

• Has excellent in vitro activity against many important Gram-negative

pathogens, including many ceftazidime-non susceptible
Enterobacteriaceae and P. aeruginosa
• Non-inferior to carbapenem comparators in cUTI/acute pyelonephritis,
cIAI (in combination with metronidazole) and HAP/VAP
• Generally well tolerated, with a tolerability profile consistent with that of
ceftazidime alone
• Administered intravenously at a fixed ceftazidime:avibactam ratio of 4:1

Drugs. 2018; 78: 675-692.

Avibactam:
first-in-class of novel β-lactamase inhibitors
• Avibactam is a novel, first-in-class, non-β-lactam β-lactamase
inhibitor from a new chemical class, diazabicyclooctane
(DBOs)
• Avibactam differs from these agents in all three respects
▪ Expanded spectrum of β-lactamase inhibition
▪ Mechanism of inhibition is reversible

Clavulanic acid Sulbactam Avibactam

Tazobactam

β-lactam ring β-lactam ring

β-lactam ring
Lahiri SD, et al. Antimicrob Agents Chemother 2013;57:2496–505.

1:1 randomization EOT
REPROVE study in HAP/VAP
Study design Ceftazidime–avibactam
(2–0.5 g, 2 h i.v. infusion, q8h)
Hospitalized adult patients Final
>18 years old with
TOC protocol
HAP/VAP* (7–14 days of therapy) follow-up
(N=817)
Meropenem
21–25 days 28–32 days
1 g, i.v. infusion, q8h
after randomization after randomization

• Prospective, randomized, multicenter, double-blind study comparing the efficacy, safety and tolerability of
ceftazidime–avibactam versus meropenem

Primary endpoint:
Proportion of patients with clinical cure at the TOC visit in the cMITT and CE analysis sets (co-primary analyses)†

*HAP defined as pneumonia with onset ≥48 h after admission or <7 days after discharge from an inpatient care facility; VAP defined as parenchymal lung infection with onset ≥48 hours after endotracheal intubation and
mechanical ventilation; Diagnosis based on clinical assessment (new worsening infiltrate on chest X-ray within 48 h of randomization), and ≥2 respiratory signs of pneumonia.
†Assessed by non-inferiority, concluded if the lower limit of the 2-sided 95% CI for treatment difference was greater than -12·5% in the co-primary cMITT and CE populations. All criteria for non-inferiority of ceftazidime–
avibactam vs meropenem were met in both co-primary analysis populations. Clinical cure defined as resolution of all signs and symptoms of pneumonia such that no antibacterial therapy for HAP was taken between EOT
and TOC inclusive.

CE, clinically evaluable; cMITT, clinically modified intent-to-treat; HAP, hospital-acquired pneumonia;
TOC, test of cure; VAP, ventilator-associated pneumonia.
Torres A, et al. Lancet Infect Dis 2018;18(3):285–95.

Analysis populations*
Safety All patients who received any amount of study therapy

All patients meeting minimum disease requirements who received any amount of study therapy, but
cMITT excluding patients with only non-target pathogens

All patients in the cMITT population who received an adequate course of treatment, had an
CE evaluable assessment, no protocol deviations that affected the assessment of efficacy and no
unacceptable prior or concomitant antibiotics

All patients in the CE population who had at least one aetiologic pathogen from an adequate
ME baseline culture that was susceptible to both ceftazidime–avibactam and meropenem

eME All patients in the CE population who had at least one aetiologic pathogen from an adequate baseline
culture regardless of susceptibility to study therapy

*Patients with moderate/severe renal impairment enrolled prior to protocol amendment to the new dosing regimen were excluded from all analysis populations

CE, clinically evaluable; cMITT, clinically modified intent-to-treat; eME, extended microbiologically
evaluable; ME, microbiologically evaluable.
Torres A, et al. Lancet Infect Dis. 2018;18(3):285–95; Supplement to: Torres A, et al. Lancet Infect Dis
2018;18(3):285–95.

879 patients randomized

62 patients with moderate/severe renal

impairment enrolled prior to protocol amendment
to the dose regimen excluded from all analyses

409 randomized to ceftazidime–avibactam 408 randomized to meropenem

4 did not receive study treatment 5 did not receive study treatment
1 patient decision 1 eligibility criteria not fulfilled
2 died 1 died
1 for other reasons 3 for other reasons

405 received ceftazidime–avibactam 403 received meropenem

50 discontinued the study

Safety (n=405) 39 discontinued the study* Safety (n=403)
8 patient decision
4 patient decision
cMITT (n=356) 37 died cMITT (n=370)
27 died
CE (n=257) 3 lost to follow-up CE (n=270)
7 lost to follow-up
eME (n=125) 2 for other reasons eME (n=131)
1 for other reasons

355 completed study (FPFU visit) 363 completed study (FPFU visit)

*One meropenem patient completed the TOC visit (outside the window) and the FPFU visit on the same day, and was considered neither to have completed the study nor discontinued the study.

CE, clinically evaluable; cMITT, clinically modified intention-to-treat; eME, extended microbiologically
evaluable; FPFU, final patient follow-up; TOC, test of cure.
Torres A, et al. Lancet Infect Dis. 2018;18(3):285–95.
 Gram-negative pathogens identified at baseline with a combined
frequency of ≥10 (mMITT population)
Patients, n (%)

Ceftazidime–avibactam Meropenem Total

(n=171) (n=184) (N=355)
Enterobacteriaceae 121 (70.8) 138 (75.0) 259 (73.0)
Klebsiella pneumoniae 59 (34.5) 71 (38.6) 130 (36.6)
Enterobacter cloacae 26 (15.2) 22 (12.0) 48 (13.5)
Escherichia coli 17 (9.9) 20 (10.9) 37 (10.4)
Serratia marcescens 15 (8.8) 13 (7.1) 28 (7.9)
Proteus mirabilis 14 (8.2) 12 (6.5) 26 (7.3)
Enterobacter aerogenes 8 (4.7) 8 (4.3) 16 (4.5)
Gram-negative pathogens other than
79 (46.2) 80 (43.5) 159 (44.8)
Enterobacteriaceae
Pseudomonas aeruginosa 58 (33.9) 47 (25.5) 105 (29.6)
Haemophilus influenzae 16 (9.4) 25 (13.6) 41 (11.5)

• Overall, 28% of isolates were ceftazidime-non-susceptible:

o 2 K. pneumoniae and 9 P. aeruginosa isolates were resistant to ceftazidime–avibactam
o 5 K. pneumoniae and 31 P. aeruginosa were non-susceptible to meropenem
mMITT, microbiologically modified intention-to-treat.
Torres A, et al. Lancet Infect Dis 2018;18(3):285–95.

Ceftazidime–avibactam was non-inferior to meropenem for the treatment of HAP/VAP in this setting

Clinical cure rate at TOC

Primary endpoint efficacy:

Patient with favorable clinical response

CE Population cMITT Population
100%
clinical cure rates at TOC (CE
90%
and cMITT populations) 77.4% 78.1%

at test of cure (%)

80% 73.0%
68.8%
70%
60%
Ceftazidime-avibactam
50%
40% Meropenem

30%
20%
10%
0%
Difference (95% CI). -0.7% Difference (95% CI). -4.2%
(-7.86, 6.39) (-10.76, 2.46)
(n=199/257) (n=211/270) (n=245/356) (n=270/370)

Adapted from: Torres A, et al. 2018

CE, clinically evaluable; cMITT, clinically modified intention-to-treat; HAP, hospital-acquired

pneumonia; TOC, test of cure; VAP, ventilator-associated pneumonia.
Torres A, et al. Lancet Infect Dis 2018;18(3):285–95.
Secondary endpoint efficacy: per-pathogen clinical cure rates and favorable
microbiological response rates
Per-pathogen eradication rates at TOC were similar between groups, with numerical
differences containing wide CIs among individual bacterial species
Patients with favorable microbiological
Patients with clinical cure at TOC (CE) response at TOC (eME)

Ceftazidime– Ceftazidime–
Meropenem Meropenem
avibactam Difference avibactam Difference
(n=270) (n=131)
(n=257) (n=125)

Enterobacteriaceae
Klebsiella pneumoniae 83.8% 79.6% 4.2% 78.4% 79.6% -1.2%
Enterobacter cloacae 95.2% 63.6% 31.6% 85.7% 63.6% 22.1%
Escherichia coli 72.7% 77.8% -5.1% 90.9% 88.9% 2.0%
Proteus mirabilis 100.0% 87.5% 12.5% 81.8% 75.0% 6.8%
Serratia marcescens 83.3% 100.0% -16.7% 75.0% 62.5% 12.5%
Enterobacter aerogenes 66.7% 40.0% 26.7% 83.3% 60.0% 23.3%
Gram-negative pathogens other than Enterobacteriaceae
Pseudomonas aeruginosa 64.3% 77.1% -12.9% 42.9% 40.0% 2.9%
Haemophilus influenzae 90.9% 84.6% 6.3% 100.0% 92.3% 7.7%
Data are patients with clinical cure/number of patients in subgroup (%) and % difference.
Torres A, et al. Lancet Infect Dis 2018;18(3):285–95.
Antimicrobial activity of ceftazidime–avibactam against MDR Enterobacteriaceae and P. aeruginosa
isolates from US medical centers (2013–2016)
% susceptibility

n=36,380 n=2,953 n=448 n=513 n=7,868 n=1,562 n=628

Enterobacteriaceae MDR MER, PIP/TAZ
MDR XDR CRE P. aeruginosa
P. aeruginosa and
EnterobacteriaceaeEnterobacteriaceae
ceftazidime-R
P. aeruginosa
CRE, carbapenem-resistant Enterobacteriaceae; MDR, multidrug resistant; PIP/TAZ, piperacillin/tazobactam;
MER, meropenem; R, resistant; XDR, extensively drug resistant.
Adapted from Sader, HS, et al. Antimicrob Agents Chemother 2017;61:e01045.
 Strategi Terapi Antibiotika pada HAP/VAP

Jean et al. J. Clin. Med. 2020, 9, 275; doi:10.3390/jcm9010275.

 Dosis rekomendasi
• The recommended dosage is 1 vial where each vial contains 2 g
ceftazidime and 0.5 g avibactam administered by intravenous (IV) infusion
in a volume of 100 ml at a constant rate over 120 minutes in patients aged
18 years or older. Treatment is repeated every 8 hours.
• For patients with renal impairment where CrCl ≤50 ml/min, see dose
recommendations below
In patients with impaired renal function,
regular monitoring of estimated creatinine
clearance is advised as in some patients,
especially early in the course of their
infection, the creatinine clearance estimated
from serum creatinine can change quickly.

Haemodialysis
Both ceftazidime and avibactam are
haemodialyzable; thus, ceftazidime-avibactam
should be administered after haemodialysis on
It
haemodialysis day.
 Ringkasan
• HAP / VAP merupakan pneumonia dengan risiko tinggi disebabkan oleh
patogen MDR
• MDRO → meningkatkan morbiditas dan mortalitas
• MDRO → sulit diobati
• Perlu strategi pencegahan terjadinya HAP dan strategi penatalaksanaan
MDRO, termasuk di dalamnya pemilihan antibiotika yang tepat
• Ceftazidime / avibactam merupakan kombinasi obat yang baru, berguna pada
kasus infeksi gram negatif yang sulit diobati, ketika pilihan antibiotika
semakin sempit atau tidak ada sama sekali
TERIMA KASIH