IJTID Vol 9 No 3 September-Desember 2021.indd Vol. 9 No. 3 September–December 2021 Available online at IJTID Website: https://e-journal.unair.ac.id/IJTID/ IJTID, p-ISSN 2085-1103, e-ISSN 2356-0991 Open acces under CC-BY-NC-SA Share alike 4.0 * Corresponding Author: budayantinns@unud.ac.id Research Article Antimicrobial Resistance Profi le of MDR & Non-MDR Meropenem- Resistant Pseudomonas aeruginosa Isolates of Patients in Intensive Care Unit of Tertiary Hospital Imaculata Sonia Vidaryo Lameng1, Ni Nyoman Sri Budayanti1,2*, Luh Inta Prilandari2, Agus Indra Adhiputra1 1Clinical Microbiology Study Program, Faculty of Medicine, Udayana University - Sanglah Hospital, Denpasar, Bali 2Clinical Microbiology Departement, Faculty of Medicine, Udayana University – Sanglah Hospital, Denpasar, Bali Received: 18th September 2021; Revised:19th October 2021; Accepted: 13th December 2021 ABSTRACT Pseudomonas aeruginosa is one of the Gram-negative bacteria that frequently causes infection of patients in the Intensive Care Unit (ICU) which is easily resistant to antimicrobial drugs. Patients infected with carbapenem-resistant P. aeruginosa are predicted to have a poor prognosis. This study aims to know the resistance profi le of meropenem-resistant P. aeruginosa of patients in the ICU. The results of this study can be used as a measure on the success of antimicrobial resistance control, infection control programs and become a reference for empirical therapy in the ICU. This study used descriptive research and was carried out at the Clinical Microbiology Laboratory of Sanglah Hospital Denpasar for three years, from 2018 to 2020. The results showed 38 of the 93 isolates of P. aeruginosa in the ICU were resistant to meropenem and were derived from sputum and urine. The percentage of meropenem-resistant P. aeruginosa isolates was higher in the multi-drug-resistant group and mostly came from sputum specimens. In 2018, Non-MDR meropenem-resistant P. aeruginosa isolates was that 100% sensitive to all other antibiotics used to treat P. aeruginosa infections, including; ceftazidime, cefepime, ciprofl oxacin, gentamicin, amikacin, and piperacillin-tazobactam. In 2019 no meropenem-resistant P. aeruginosa isolates were found. In 2020, its sensitivity to antibiotics ceftazidime and piperacillin-tazobactam was 20.0%, ciprofl oxacin 60.0% and to antibiotics gentamicin and amikacin 100%. MDR meropenem-resistant P. aeruginosa isolates in 2018 were still sensitive to ceftazidime (15.4%) and amikacin (69.2%) antibiotics, while in 2019 they were only sensitive to amikacin (37.5%). In 2020, P. aeruginosa isolates were sensitive to the antibiotics ceftazidime and cefepime (11.1%), piperacillin-tazobactam (22.2%), and amikacin (88.9%). Amikacin may be the choice of treatment for MDR meropenem-resistant P. aeruginosa. Keywords: Resistance Profi le; Pseudomonas aeruginosa; ICU; Meropenem; Resistance ABSTRAK Pseudomonas aeruginosa merupakan salah satu bakteri Gram negatif penyebab infeksi pada pasien di Intensive care unit (ICU) yang mudah resisten. Pasien terinfeksi P. aeruginosa yang resistan karbapenem diindikasikan memiliki prognosis yang buruk. pengendalian infeksi dan menjadi acuan pemberian terapi empiris di ICU. Penelitian ini menggunakan metode penelitian deskriptif dan dilakukan di Instalasi Mikrobiologi Klinik Rumah Sakit Sanglah Denpasar selama tiga tahun, dari 2018 hingga 2020. Hasil penelitian menunjukan 38 dari 93 isolat P. aeruginosa di ICU resistan terhadap meropenem dan berasal dari spesimen sputum dan urine. Presentasi isolat P. aeruginosa yang resistan meropenem lebih tinggi pada kelompok multi-drug resistan dan sebagian besar berasal dari spesimen sputum. Pada tahun 2018, isolat P. aeruginosa Non-MDR yang resistan meropenem, 100% sensitif terhadap semua antibiotik lainnya yang digunakan untuk terapi infeksi P. aeruginosa, antara lain ; ceftazidime, cefepime, ciprofl oxacin, gentamicin, amikacin, dan piperacillin-tazobaktam. Pada tahun 2019 tidak ditemukan isolat P. aeruginosa Non-MDR resistan meropenem. Pada tahun 2020, sensitifi tasnya terhadap antibiotik ceftazidime dan piperacillin-tazobactam 20,0%, ciprofl oxacin 60,0% dan terhadap antibiotik gentamicin serta amikacin 100%. Isolat P. aeruginosa MDR resistan meropenem pada tahun 2018 masih sensitif terhadap antibiotik ceftazidime (15,4%) dan amikacin (69,2%), sedangkan pada tahun 2019 hanya sensitif terhadap antibiotik amikacin (37,5%). Pada IJTID, p-ISSN 2085-1103, e-ISSN 2356-0991 Open acces under CC-BY-NC-SA Share alike 4.0 tahun 2020, isolat P. aeruginosa sensitif terhadap antibiotik ceftazidime dan cefepime (11,1%), piperacillin-tazobactam (22,2%), serta amikacin (88,9%). Amikacin dapat menjadi pilihan terapi P. aeruginosa MDR resistan meropenem. Kata kunci: Profi l Resistansi; Pseudomonas aeruginosa; ICU; Meropenem; Resistansi How to Cite: Lameng, I.S.V, Budayanti, N.N.S, Prilandari, L.I, Adhiputra, A.I. Antimicrobial Resistance Profi le of MDR & Non-MDR Meropenem-Resistant Pseudomonas aeruginosa Isolates of Patients in Intensive Care Unit of Tertiary Hospital. Indonesian Journal of Tropical and Infectious Disease, 9(3) INTRODUCTION Pseudomonas aeruginosa is one of the gram- negative bacteria that is often found as a contaminant in hospitals.1,2 This bacterium can be an opportunistic pathogen causing nosocomial infections in the blood, lungs, and other body parts after surgery, especially in immunocompromised patients, patient received appropriate medical procedure, invasive, surgical wound or burns.2,3 Nosocomial infections are estimated to occur annually in 1.75 million hospitalized patients worldwide and result in 175,000 deaths.4 P. aeruginosa accounts for 10%- 20% of Hospital Acquired Infections in Europe.5 The National Healthcare Safety Network (NHSN) reported, P. aeruginosa as the third most common gram-negative bacteria causing nosocomial infections during 2011-2014.6,7 Research by Ribeiro et al. from January 2010 to December 2013 found that P. aeruginosa was the second most common bacterium in the ICU Sao Paulo Hospital Brazil (14.5%), of which 48.7% was multi-resistant drug organism.8 At Sanglah Hospital itself in the second half of 2020, P. aeruginosa ranked third highest bacteria that cause infection in the Intensive Care Unit (ICU) and High Care Unit (HCU).9 Patients admitted to the ICU have a fi ve to ten times higher risk of developing P. aeruginosa infection compared to patients admitted to other inpatients.10 High frequency infection in the ICU is associated with a decrease in the patient’s immunity due to the disease and the use of invasive devices such as catheters, nasogastric tubes, and ventilators.3,10 P. aeruginosa has quorum sensing ability which is associated with the occurrence of biofi lms on invasive medical devices in patients in the ICU.1,2 The spread of P. aeruginosa infection through person-to-person contact is also more prone to occur in the ICU due to several factors a patient is combined in one relatively small room.10 In the management of infection therapy, the selection of empiric antibiotics in the ICU is not easy.4 According to Performance Standard for Antimicrobial Susceptibility Testing on Clinical and Laboratory Standard Institute (2021), P. aeruginosa sensitive to antibiotics, beta-lactam combinations such as piperacillin tazobactam, 3rd generation cephalosporins especially ceftazidime, 4th generation cephalosporins (cefepime), aminoglycosides (gentamicin, amikacin), monobactams (aztreonam), carbapenems (except ertapenem) and fl uoroquinolones (ciprofl oxacin).11 The aztreonam group often becomes resistant.1 Treatment of infectious diseases caused by P. aeruginosa becomes difficult because P. aeruginosa is easily resistant to various types of antibiotics. The prevalence of P. aeruginosa resistance to antibiotics is higher in ICU patient isolates compared to non ICU patients.10,12 The irresponsible use of an antibiotic widely, repeatedly, and over a long period of time can lead to the emergence of antibiotic resistance.10 The increase in treatment costs in cases of infection due to resistant bacteria is caused by various factors, including; patients get longer treatment, longer hospital stays, more intensive attention from health professionals such as doctors and nurses, or the use of newer antibiotics. Newer antibiotics generally cost more than older antibiotics. The potential for increased costs in overcoming cases of infection by resistant bacteria needs attention because it can increase the fi nancial burden that must be borne by the state in the era of implementing the National Health Insurance program (JKN). 14 Carbapenem is a type of beta-lactam antibiotic which has a broad spectrum of antibacterial Imaculata Sonia Vidaryo Lameng, et al.: Antimicrobial Resistance Profile of MDR & Non-MDR 153 IJTID, p-ISSN 2085-1103, e-ISSN 2356-0991 Open acces under CC-BY-NC-SA Share alike 4.0 activity.14 Carbapenems such as meropenem and imipenem are potential antimicrobial agents that also used to treat Multi-Drug Resistant Pseudomonas aeruginosa (MDRPA) infections.14,15 Increasing resistance to carbapenem antibiotics is one of the phenomena that must be watched out for at this time. Patients infected with carbapenem-resistant P. aeruginosa are indicated to have a poor prognosis.16 This study aims to know the resistance profi le of meropenem-resistant P. aeruginosa in the ICU. The results of this study can be used as a measure on the implementation of antimicrobial resistance control, infection control programs and become a reference for empirical therapy in the ICU. MATERIAL AND METHODS This study used a descriptive research and was conducted at the Clinical Microbiology Laboratory of Sanglah Hospital Denpasar for three years, from 2018 to 2020. Sanglah Hospital Denpasar is a tertiary referral hospital and the main health care center for the eastern part of Indonesia with facilities of 710 beds. The sample was clinical isolates of meropenem- resistant P. aeruginosa from patients admitted to ICU. All type of specimens were included in this study. Identifi cation and antimicrobial susceptibility testing were conducted using the VITEK 2 automated system with GN card for identifi cation and AST GN 93 for antimicrobial susceptibility testing, according to the 2020 Clinical Laboratory Standard Institute (CLSI) standard.11,17 Data of antibiotic susceptibility test were collected and resistance profi le was analyzed. Meropenem-resistant P. aeruginosa is a P. aeruginosa isolate with a minimum inhibitory concentration of ≥ 8 g/mL based on a dosage regimen of 1 gram every 8 hours.11 The antibiotics assessed in this study were the antibiotics of choice for P. aeruginosa that were available and included in the Sanglah Hospital formulary, including piperacillin tazobactam, ceftazidime, cefepime, gentamicin, amikacin, and ciprofl oxacin.18 Multidrug-resistant (MDR) is a condition in which bacteria are resistant to at least one type of antibiotic from 3 antibiotic groups.13 MDR P. aeruginosa is a P. aeruginosa isolate that is resistant to at least one of three or more classes of antibiotics of choice for this bacterium, including: quinolones (ciprofl oxacin), extended-spectrum cephalosporins (ceftazidime, cefepime), penicillin (piperacillin tazobactam), aminoglycosides (gentamicin or amikacin) and carbapenems (meropenem).11,13 The exclusion criteria were incomplete data on meropenem- resistant P. aeruginosa isolates from the ICU including the results of antibiotic sensitivity tests as well as data from other treatment rooms including the COVID-19 special ICU. RESULTS This study observe the sensitivity pattern of meropenem-resistant P. aeruginosa in 3 consecutive years, from 2018 to 2020. In general, from 2018 to 2020, 93 P. aeruginosa bacteria were isolated in the ICU Sanglah Hospital Denpasar. The number of non-multidrug-resistant (Non- MDR) P. aeruginosa isolates in the ICU showed an increasing number but the MDR isolates showed a decreasing number (Figure 1). Figure 1. Pseudomonas aeruginosa in ICU during the period of 2018-2020 Most of the P. aeruginosa isolates came from sputum specimens, both Non-MDR and MDR, followed by urine and blood specimens. MDR P. aeruginosa isolates in 2018, 100% came from sputum specimens, while in 2019 and 2020, specimens came from sputum and urine specimens (Table I). Indonesian Journal of Tropical and Infectious Disease, Vol. 9 No. 3 September–December 2021: 152–159 FIRDA Typewritten text 154 IJTID, p-ISSN 2085-1103, e-ISSN 2356-0991 Open acces under CC-BY-NC-SA Share alike 4.0 Table I. Pseudomonas aeruginosa in ICU during the period of 2018-2020 based on specimen Specimen 2018 (%) 2019 (%) 2020 (%) Non-MDR MDR Non-MDR MDR Non-MDR MDR Sputum 9(81.8) 15(100) 19(100) 9(81.8) 25(89.3) 8(88.9) Blood 2(18.2) 0(0) 0(0) 0(0) 0(0) 0(0) Urine 0(0) 0(0) 0(0) 2(18.2) 3(10.7) 1(11.1) Total 11(100) 15(100) 19(100) 11(100) 28(100) 9(100) Of the 93 isolates of P. aeruginosa in the ICU, 38 (40.9%) isolates had developed resistance to meropenem. The meropenem-resistant isolates were obtained from sputum and urine specimens. There were no meropenem-resistant isolates from blood. In 2018, 16 isolates were found from sputum, of which 3 of 9 (33.3%) were Non-MDR and 13 of 15 (86.7%) MDR. In 2019, 8 of 11 MDR isolates were resistant against meropenem, which was 66.7% in sputum and 100% in urine. In the Non-MDR group, no meropenem-resistant isolates were found. In 2020, the number of meropenem- resistant isolates were 14 isolates, 5 Non-MDR isolates came from sputum (20.0%) and 9 isolates from MDR, of which 8 isolates from sputum (100%) and 1 isolate from urine (100%). The percentage of meropenem-resistant P. aeruginosa isolates was higher in the MDR group (Figure 2). Based on table II, in 2018, Non-MDR meropenem-resistant P. aeruginosa isolates was 100% sensitive to all other antibiotics used to treat P. aeruginosa infections, including; ceftazidime, cefepime, ciprofl oxacin, gentamicin, amikacin, and piperacillin-tazobactam. In 2019 no meropenem-resistant P. aeruginosa isolates were found. In 2020, the percentage of sensitivity of other antibiotics used to treat P. aeruginosa infection decreased dramatically compared to 2018, especially ceftazidime and piperacillin- tazobactam (20.0%), followed by ciprofl oxacin (60.0%) while the sensitivity to gentamicin and amikacin was still 100%. MDR meropenem- resistant P. aeruginosa isolates in 2018 were still sensitive to ceftazidime (15.4%) and amikacin (69.2%). In 2019, MDR meropenem-resistant isolates of P. aeruginosa were only 37.5% sensitive to amikacin. The percentage was decreasing compared to 2018 and other antibiotics were already resistant. However, in 2020 the Table II. Results of antibiotic susceptibility test of meropenem-resistant P. aeruginosa isolates in 2018-2020 No Antibiotics Non-MDR(%S) MDR(%S) 2018(N=3) 2019(N=0) 2020(N=5) 2018(N=13) 2019(N=8) 2020(N=9) 1 Ceftazidime 3/3 (100) 0/0 1/5 (20.0) 2/13 (15.4) 0/8 (0.0) 1/9 (11.1) 2 Cefepime 3/3 (100) 0/0 1/5 (100) 0/13 (0.0) 0/8 (0.0) 1/9 (11.1) 3 Ciprofl oxacin 3/3 (100) 0/0 3/5 (60.0) 0/13 (0.0) 0/8 (0.0) 0/9 (0.0) 4 Gentamicin 3/3 (100) 0/0 5/5 (100) 0/13 (0.0) 0/8 (0.0) 0/9 (0.0) 5 Amikacin 3/3 (100) 0/0 5/5 (100) 9/13 (69.2) 3/8 (37.5) 8/9 (88.9) 6 Piperacilin tazobactam 3/3 (100) 0/0 1/5 (20.0) 0/13 (0.0) 0/8 (0.0) 2/9 (22.2) Figure 2. Meropenem-resistant Pseudomonas aeruginosa in ICU (N=38 isolates) Imaculata Sonia Vidaryo Lameng, et al.: Antimicrobial Resistance Profile of MDR & Non-MDR 155 IJTID, p-ISSN 2085-1103, e-ISSN 2356-0991 Open acces under CC-BY-NC-SA Share alike 4.0 sensitivity of meropenem-resistant P. aeruginosa isolates to antibiotics improved, including to the ceftazidime and cefepime (11.1%), piperacillin- tazobactam (22.2%), and amikacin (88.9%). The sensitivity pattern of MDR meropenem- resistant P. aeruginosa isolates (Table 3) showed that there was a pattern of MDR meropenem- resistant P. aeruginosa isolates that were also resistant to all antibiotics in the hospital. This pattern always exists every year with a fl uctuating percentage and a signifi cant decline in 2021. The pattern of MDR meropenem-resistant P. aeruginosa isolates sensitive to ceftazidime and amikacin antibiotics was only found in 2018. In 2021, the pattern of antibiotic sensitivity was more diverse. Most of them were resistant to various antibiotics, but each of these sensitivity patterns was still sensitive to amikacin antibiotics and one isolate of MDR P. aeruginosa was meropenem- resistant, besides being sensitive to amikacin, they were also sensitive to the ceftazidime, cefepime, piperacilin, tazobactam antibiotics. The Non- MDR meropenem-resistant P. aeruginosa isolate in 2018, the sensitivity pattern of 100% showed sensitivity to all anti-pseudomonal antibiotics Table III. Resistance profi le of MDR and Non-MDR meropenem-resistant P. aeruginosa isolates C ef ta zi di m e C ef ep im e P ip er az ili n ta zo ba ct am C ip ro fl o xa ci n G en ta m ic in A m ik ac in 2018 2019 2020 No Meropenem-Resistant Pseudomonas aeruginosa MDR(%) MDR(%) MDR(%) 1 S R R R R S 2/13 (15.4) 0/8 (0.0) 0/9 (0.0) 2 R R R R R S 5/13 (58.8) 3/8(37.5) 6/9 (66.7) 3 R R R R R R 4/13 (30.8) 5/8 (62.5) 1/9 (11.1) 4 R R S R R S 0/13 (0.0) 0/8 (0.0) 1/9 (11.1) 5 S S S R R S 0/13 (0.0) 0/8 (0.0) 1/9 (11.1) No Meropenem-Resistant Pseudomonas aeruginosa Non-MDR (%) Non-MDR (%) Non-MDR (%) 1 S S S S S S 3/3 (100) 0/0 1/5 (20.0) 2 R R R R S S 0/3 (0.0) 0/0 2/5 (40.0) 3 R R R S S S 0/3 (0.0) 0/0 2/5 (40.0) available at Sanglah Hospital Denpasar. However, in 2020, the pattern of sensitivity to antibiotics varied because some antibiotics were already resistant. DISCUSSION Pseudomonas aeruginosa is one of the environmental bacteria that is often found in hospitals.1,2 These bacteria can be opportunistic pathogens that cause nosocomial infections, including pneumonia, urinary tract infections, sepsis, osteomyelitis and skin infections including wounds and burns.2 P. aeruginosa can grow in a variety of environmental conditions. Incidence of infection and resistance is common in the ICU. The bacteria found were often resistant to antibiotics.10,19 Based on data from the antibiogram of Sanglah Hospital for the July- December 2020 period, P. aeruginosa was the third highest bacteria in the ICU and HCU.9 The high rate of frequency of P. aeruginosa in the ICU is related to the decreased immunity itself, as well as the use of invasive devices such as catheters, nasogastric tubes and ventilators.3,10 Indonesian Journal of Tropical and Infectious Disease, Vol. 9 No. 3 September–December 2021: 152–159 FIRDA Typewritten text 156 IJTID, p-ISSN 2085-1103, e-ISSN 2356-0991 Open acces under CC-BY-NC-SA Share alike 4.0 According to the Performance Standard for Antimicrobial Susceptibility Testing at the 2020 edition of the Clinical and Laboratory Standard Institute, P. aeruginosa is sensitive to beta lactam combination antibiotics such as piperacillin tazobactam, 3rd generation cephalosporins especially ceftazidime, 4th g e n e r a t i o n c e p h a l o s p o r i n ( c e f e p i m e ) , aminoglycosides (gentamicin, amikacin), monobactam (aztreonam), carbapenems (except ertapenem) and fl uoroquinolones.11 The aztreonam group often becomes resistant.1 Widespread, repeated, and long-term use of an antibacterial agent can lead to the emergence of antibacterial resistance.15 P. aeruginosa is intrinsically resistant to several antibiotics and has the ability to rapidly generate resistance to new antimicrobials. P. aeruginosa was the fi rst bacterium to show an MDR phenotype.8 Carbapenem antibiotics have become important in clinical management.8,20 Carbapenem-resistant P. aeruginosa infections are common.21 In February 2017, the World Health Organization made a priority list of pathogenic bacteria in the development of new antibiotics. Carbapenem-resistant P. aeruginosa is second ranked in the group of top priority (critical) bacteria because of its high resistance to most antibiotics including carbapenems and third- generation cephalosporins which are the best choices in the treatment of MDR bacteria.22 In the United States, 10%–20 % of clinical isolates of P. aeruginosa identifi ed in health facilities, resistant to at least one carbapenem group antibiotic.23 P. aeruginosa became meropenem-resistant due to upregulation of the effl ux pump.24 In this study, the percentage of meropenem- resistant P. aeruginosa isolates was higher in the multidrug-resistant group and most of them came from sputum specimens. Most of the sputum specimens collected in this study were from endotracheal tube secretions. P. aeruginosa has the ability of a bacterial cell-cell communication mechanism, known as quorum sensing (QS) which plays a role in gene expression and biofi lm formation. The results of this study also support research in New York by Walter et al., that during July-October 2015 carbapenem-resistant P. aeruginosa was most commonly found in sputum specimens followed by urine.18 Research by Asempa TE et al., in 2017-2018 also showed that 89% meropenem-resistant P. aeruginosa was found in respiratory specimens.25 The sensitivity of meropenem-resistant P. aeruginosa isolates varied to various antibiotics. Research carried out by Vitkauskienė A et al., in 2003 and 2008, isolates of P. aeruginosa that were resistant to carbapenems were more often resistant to ciprofl oxacin and gentamicin than isolates sensitive to carbapenems. In 2008, isolates that were carbapenem-resistant were also more frequently resistant to ceftazidime, cefepime, aztreonam, piperacillin, and amikacin.26 Results from the study by Asempa TE et al. in July-October 2017 showed that most of the carbapenem-resistant P. aeruginosa isolates had lower resistance to ceftazidime.25 Research by Garcinuno et al. The data from 2009-2013 found that most of the meropenem-resistant P. aeruginosa isolates were also resistant to fl uoroquinolones. Administration of amikacin therapy resulted in a more than threefold reduction in the risk of resistance.27 Overuse of fl uoroquinolones in the treatment of P. aeruginosa infections increased bacterial resistance to fluoroquinolones in recent years. Resistance to fl uoroquinolones is mainly due to: (1) point mutations in the DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) genes, (2) the presence of transferable plasmid-mediated quinolone resistance (PMQR), and (3) mutations in genes that regulate efflux expression and decreased expression of outer membrane porins.28 From the results of this study, in 2018 Non-MDR meropenem-resistant P. aeruginosa isolates were still sensitive to all antibiotics but in 2020 most of the sensitivity patterns showed sensitivity to gentamicin and amikacin. Although the MDR meropenem-resistant isolates of P. aeruginosa showed less sensitivity to various antibiotics, in 2020 the percentage of sensitivity to antibiotics except ceftazidime increased. Sanglah Hospital published Guidelines for the Use of Prophylactic and Therapeutic Antibiotics in 2019, ceftazidime is included in the Watch group of antibiotics. Ceftazidime not recommended as empiric Imaculata Sonia Vidaryo Lameng, et al.: Antimicrobial Resistance Profile of MDR & Non-MDR 157 IJTID, p-ISSN 2085-1103, e-ISSN 2356-0991 Open acces under CC-BY-NC-SA Share alike 4.0 antibiotic therapy but should be based on the results of bacterial culture (defi nitive therapy) to P. aeruginosa, so its use restricted, in which allows the sensitivity P. aeruginosa to the ceftazidime increased in Sanglah hospital. This can be seen in the pattern of sensitivity, where although there is a pattern that is already resistant to all antibiotics every year, the percentage shows a fl uctuating picture and signifi cantly decreases in 2020. In addition, there were various other sensitivity patterns that showed MDR meropenem-resistant P. aeruginosa isolates were still sensitive to amikacin. The results of this study support the statement of Baseti et al. in 2018 which stated that all antipseudomonal antibiotics except amikacin were associated with the emergence of resistance in P. aeruginosa. Aminoglycosides modifying enzymes (AME) inactivate aminoglycosides by attaching acetyl, phosphate or adenyl groups to the amino and hydroxyl substituents on the antibiotic molecule. This modifi cation signifi cantly reduced the affi nity of the aminoglycoside for the target of the 30S ribosomal subunit and blocks the activity of the aminoglycoside. However, compared to other aminoglycosides, amikacin is usually a poor substrate for this enzyme and is known to provide better antibiotic activity against P. aeruginosa.28 The results of this study also support the study carried out by Khan F et al. in 2012-2013 regarding the Prevalence and Susceptibility Pattern of Multi Drug Resistant Clinical Isolates of Pseudomonas aeruginosa in Karachi and research by Anggraini D et al., regarding the Prevalence and Sensitivity Pattern of Multidrug Resistant Antimicrobial Pseudomonas aeruginosa in Arifin Achmad Pekanbaru Hospital in 2015 that amikacin is a therapeutic option for MDR P. aeruginosa.29,30 CONCLUSION The resistance profi le of meropenem-resistant P. aeruginosa in the ICU varies. Meropenem- resistant P. aeruginosa isolates that were Non- MDR for 3 years were still mostly sensitive to gentamicin and amikacin, while in multi-drug resistant isolates, amikacin was the choice of treatment. ACKNOWLEDGEMENT The authors are grateful for cooperation of: 1. Head and all staff Clinical Microbiology of Sanglah Hospital. 2. Antimicrobials Resistance Control Sub Committee of Sanglah Hospital. CONFLICT OF INTEREST REFERENCES 1. Ryan KJ, Ahmad N, Alspaugh JA, Drew WL, Reller M. Sherris Medical Microbiology. 7th ed. New York: McGraw Hill Education; 2014. 2. Talaro KP, Chess B. Foundation Microbiology. 10th ed. New York: McGraw-Hill Education; 2018. 3. Centers for Disease Control and Prevention. Pseudomonas aeruginosa in Healthcare Settings [Internet]. Centers for Disease Control and Prevention; 2019 [cited 29 April 2021]. Available from: https://www.cdc.gov/hai/ organisms/pseudomonas.html 4. Guggenbichler JP, Assadian O, Boeswald M, Kramer A. Incidence and clinical implication of nosocomial infections associated with implantable biomaterials - catheters, ventilator-associated pneumonia, urinary tract infections. GMS Krankenhhyg Interdiszip. 2011;6(1). doi: 10.3205/dgkh000175 5. 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