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Article

The Characterisation of Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in a Teaching Hospital in Malaysia

by
Min Yi Lau
1,
Sasheela Ponnampalavanar
2,3,*,
Chun Wie Chong
4,
Jacky Dwiyanto
1,
Yee Qing Lee
1,
Jia Jie Woon
1,
Zhi Xian Kong
1,
Azmiza Syawani Jasni
5,
Michelle Chin Chin Lee
6,
Unaizah Hanum Obaidellah
7 and
Cindy Shuan Ju Teh
1,*
1
Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia
2
Infectious Disease Unit, Department of Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia
3
Department of Infectious Control, Universiti Malaya Medical Centre, Kuala Lumpur 50603, Malaysia
4
School of Pharmacy, Monash University Malaysia, Subang Jaya 47500, Malaysia
5
Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia
6
School of Psychology, Massey University, Albany, Auckland 0745, New Zealand
7
Department of Artificial Intelligence, Faculty of Computer Science and Information Technology, University Malaya, Kuala Lumpur 50603, Malaysia
*
Authors to whom correspondence should be addressed.
Antibiotics 2024, 13(11), 1107; https://doi.org/10.3390/antibiotics13111107
Submission received: 18 October 2024 / Revised: 15 November 2024 / Accepted: 18 November 2024 / Published: 20 November 2024
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Abstract

:
Background/Objectives: The emergence and dissemination of carbapenem-resistant organisms, particularly Acinetobacter baumannii and Klebsiella pneumoniae, pose a significant threat to healthcare systems worldwide. This retrospective study aims to characterise carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains in a teaching hospital and to determine the risk factors associated with patients’ in-hospital mortality. Methods: A total of 90 CRAB and 63 CRKP were included in this study. Carbapenemase genes and MLST types of CRAB and CRKP were determined using specific primers. Risk factors associated with in-hospital mortality were analysed with collected data. Results: All the CRAB strains consisted of OXA carbapenemase genes, with 98% of the strains co-harbouring blaOXA-23-like and blaOXA-51-like carbapenemase genes. Conversely, blaNDM is the predominant carbapenemase gene in CRKP, followed by blaOXA-48-like carbapenemase genes. ST2 and ST20 are the dominant MLST types in CRAB and CRKP, respectively. In CRAB, multivariate analysis identified age, ethnicity, the presence of a mechanical ventilator, and patients who experienced previous exposure to clindamycin in the last 90 days as associated with an increased risk of in-hospital mortality. In contrast, older age, male, ICU admission, and the presence of an indwelling urinary catheter were significantly associated with an increased risk of mortality for patients with CRKP. Conclusions: Both CRAB and CRKP lead to high rates of mortality. The MLST profile showed that the genomic patterns of CRKP were highly diverse, whereas CRAB strains had low genetic diversity. To tackle these challenging pathogens, robust surveillance and an in-depth understanding of molecular epidemiology and genomics studies are needed to tailor infection control strategies and individualise treatment approaches.

1. Introduction

Carbapenem is commonly used as the ‘last line’ antibiotic to treat severe antimicrobial-resistant Gram-negative infections [1]. However, in recent decades, there has been a notable increase in the prevalence of Carbapenem-resistant organisms (CROs) worldwide, particularly carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP), highlighting a concerning trend in antimicrobial resistance [2]. CRAB and CRKP have been listed as critical pathogens in the World Health Organization (WHO) priority list of antibiotic-resistant bacteria [3]. Carbapenem-resistant Enterobacterales (CRE), A. baumannii, and ESBL K. pneumoniae are the top three healthcare-associated multidrug-resistant organisms (HA-MDRO) in Malaysia hospitals [4]. It has become a major concern for public health.
Several mechanisms drive carbapenem resistance among Gram-negative bacteria. These include the production of carbapenemases, the loss or alteration of outer membrane porin, the influence of efflux pump and hyperproduction, or the depression of Amp C β-lactamases [5]. In Gram-negative bacteria, the primary factor contributing to resistance is the presence of β-lactamases (carbapenemases) [6]. Class D carbapenemase (oxacillinase), including blaOXA-23-like, blaOXA-24-like, and blaOXA-58-like, are the most prevalent genes and formed the major cause of carbapenem resistance in A. baumannii [7]. In contrast, the key mechanisms contributing to carbapenem resistance in CRKP include all classes of carbapenemase, such as Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), and OXA-type beta-lactamases [8]. These enzymatic activities disrupt the bactericidal action of carbapenems, leading to treatment failures and limited therapeutic options. Understanding the production of carbapenemase genes in CROs is crucial for developing effective strategies to combat the spread of this multidrug-resistant pathogen and ensure optimal patient care.
The number of CRKPs has doubled from 2016 to 2021, while an increase in CRAB has been observed in hospitals in Malaysia. According to the National Surveillance of Antimicrobial Resistance (NSAR) in Malaysia, the prevalence of A. baumanii resistant to meropenem has risen from 41.1% in 2018 to 63.3% in 2022 [9]. Besides that, the prevalence of CRKP resistant to meropenem also significantly increased from 0.3% in 2011 to 5.0% in 2022 [9]. Approximately 2500 CRE cases were reported in Malaysia hospitals in 2022, of which almost half were due to infection, and the mortality rate was 34% [10]. Despite the rising number of cases of CRAB and CRKP in Malaysia, comprehensive data related to its epidemiology remain scarce. To address this, we studied the epidemiology, resistance mechanisms, and risk factors associated with CRKP and CRAB in a tertiary teaching hospital in Kuala Lumpur. The result of this study will be crucial in devising effective infection control measures, optimising treatment strategies, and preventing further dissemination of these antibiotic-resistant strains in healthcare facilities and the community.

2. Results

2.1. Overview of CRAB Cases

A total of 90 CRAB strains were retrospectively collected in the years 2019 and 2020. The sample sources include wound swabs, sacral swabs, tracheal secretions, sputum, bronchoalveolar lavage, and others. This study comprised 90 patients, including individuals of Malay (26.7%), Chinese (28.9%), and Indian descent (36.7%), as well as other racial groups (7.8%), with 60 male (66.7%) and 30 female (33.3%) patients (Table 1). The mean age of the patients was 54.8, ranging from 1 month to 88 years old. A total of 42 patients (46.7%) passed away while receiving hospital care, and the remaining 48 patients recovered or were discharged from the hospital. A total of 36 (40.0%) patients were colonised with CRAB, and 54 (60.0%) were infected with CRAB.
Nearly 98% of the patients had been exposed to antibiotics in the past 90 days before the isolation of CRAB. The most common antibiotics were piperacillin-tazobactam (65.6%), meropenem (50.0%), augmentin/unasyn (42.2%), and vancomycin (42.2%). A total of 47 (87.0%) of the 54 infected patients were prescribed empiric antibiotics. Seven patients did not receive empiric treatment because they passed away on the day of diagnosis or the attending doctor opted not to treat the patient with systemic antibiotics. Meropenem (42.6%) and piperacillin-tazobactam (31.9%) were the frequently used empiric antibiotics treatment in this study. A total of 93.6% of treatment were inappropriate. Three patients received appropriate empiric treatment, whereby two patients received polymyxin B monotherapy and one patient received a combination of polymyxin B with meropenem. After obtaining culture results, 40 of 54 patients received definitive treatment, of which 36 (90.0%) were appropriate. This included polymyxin monotherapy (n = 5, 12.5%) and polymyxin combination therapy (n = 29, 72.5%). The combination therapy of polymyxin B and meropenem (n = 5, 12.5%) or polymyxin B and ampicillin-sulbactam (n = 18, 45.0%) was frequently used to treat CRAB in the hospital setting. Ten patients did not receive definitive treatment as they died or were discharged before microbiological susceptibility results were available. Three patients with superficial skin or soft tissue infection were not treated with systemic antibiotic.
A total of 90 CRAB patients with complete data were included in the R statistical analysis. Univariate analysis indicated that factors including age, ethnicity, the presence of a mechanical ventilator, cardiovascular disease, and previous exposure to clindamycin and meropenem were significantly associated with in-hospital mortality (p value < 0.1) and were included in the multivariate models (Table 2). The multivariate model showed that age, ethnic, mechanical ventilation, and patients who had previous exposure to clindamycin in last 90 days (AIC: 110.76) were associated with an increased risk of in-hospital mortality.

2.2. Overview of CRKP Cases

Sixty-three CRKP strains were collected from rectal swabs, blood, tracheal secretion, urine, sputum, pus, and aspirate. This study comprised 63 patients, including individuals of Malay (39.7%), Chinese (33.3%), and Indian descent (20.6%), as well as other racial groups (6.3%), with the majority of 39 male (61.9%) patients (Table 1). A total of 28.6% of the patients died during hospital admission. Forty-seven (74.6%) of the patients were colonised, whereas the remaining were infected (n = 16, 25.4%). Of the 63 patients, 48 (76.2%) were admitted to ICU during hospitalisation.
A total of 96.8% of the patients had exposure to antibiotics in the last 90 days prior to CRKP isolation. The most common antibiotics they were exposed to were piperacillin-tazobactam (52.4%), meropenem (46.0%), augmentin/unasyn (41.3%), and third-generation cephalosporin (34.9%). A total of 15 of the 16 infected patients received empiric antibiotics, of which 13 (86.7%) were inappropriate. Three patients received appropriate empiric treatment, with one polymyxin B and meropenem combination therapy and two meropenem therapies. After antibiotic susceptibility test results were available, 14 of the patients received definitive treatment, of which 10 (71.4%) were appropriate. One patient received polymyxin monotherapy, eight patients received polymyxin and meropenem combination therapy, and one patient received meropenem monotherapy appropriately. Four patients received inappropriate antibiotics such as meropenem, augmentin, and piperacillin-tazobactam. Two patients died after isolation, and therefore, no treatment was given.
Univariate analysis CRKP cases indicated that age, gender, ICU admission, the use of an invasive device (such as indwelling urinary catheter, mechanical ventilator, central venous catheter, and NG tubes), comorbidity (diabetes mellitus and malignancy), and previous exposure to vancomycin and macrolides were significantly associated with patient in-hospital mortality (p-value < 0.1). These predictors were then included in the multivariate analysis, which showed that gender; patients with invasive devices, including central venous catheters, mechanical ventilators, and NG tubes; patients with malignancy; and previous exposure to macrolides are associated with a high risk of in-hospital mortality. However, an infinity 95% CI was obtained in this model; hence, high-probability predictors, including the use of a mechanical ventilator, central venous catheter, NG tubes, and malignancy, were excluded from the multivariate analysis. The final multivariate model showed that a combination of older age, male patients, admission to ICU, and indwelling urinary catheters is significantly associated with increased risk of mortality (AIC 68.89).

2.3. Determination of Carbapenemase Genes Among CRAB and CRKP Strains

All CRAB strains harboured at least one carbapenemase gene, with nearly 98% co-harbouring dual carbapenemase genes blaOXA-23 and blaOXA-51. The blaOXA-58 was detected in 2 of the 90 CRAB strains. It is noteworthy that the carbapenem-hydrolysing Class D lactamase (CHDL) genes were the only carbapenemase genes found in A. baumannii isolated from UMMC.
Among 63 CRKP strains, 73% harbour carbapenemase genes, with blaNDM (71.7%) as the predominant carbapenemase gene, followed by blaOXA-48 (6.3%). No carbapenemase genes were detected in 17 CRKP strains (27%). blaKPC, blaVIM, and blaIMP were not detected in this study, but one CRKP strain that carried dual carbapenemase genes (blaNDM + blaOXA48) was detected.

2.4. Genetic Relatedness of CRAB and CRKP Strains

ST2 (77.53%) was the dominant MLST type of CRAB in this study (Figure 1), followed by other STs, including ST164, ST642, ST25, ST81, ST643, and ST150.
The MLST profile of CRKP is genetically diverse as compared to the CRAB profile (Figure 2). ST20 (16.13%) was the most prevalent MLST type in CRKP strains, followed by ST17 (11.29%). Other STs included three or fewer strains in each ST. CRKP strains showed 35 different sequence types.
BURST analysis was conducted to visualise the MLST data set into groups of related strains and clonal complexes. STs were grouped together only if they shared five or more matches of the seven loci with at least one ST in the group. In CRAB strains, only one group was identified, which is ST642 and ST81 as DLV, whereas other STs were singletons. Six groups were identified for CRKP strains. All in all, 19 singletons were detected from the CRKP strains.
The relationships between each ST are represented in MST (Figure 3). The numbers on the connecting line between each STs correspond to the numbers of allelic differences.

2.5. Antimicrobial Susceptibility Profiles and Modified Hodge Test

The complete antimicrobial susceptibility profiles for 84 CRAB and 62 CRKP strains are summarised in Table 3. All the CRAB strains were resistant to cefepime, imipenem, meropenem, and ampicillin-sulbactam, and more than 80% of the strains were resistant to amikacin, ceftazidime, ciprofloxacin, ceftriaxone, cefotaxime, and gentamicin. Ertapenem and trimethoprim-sulfamethoxazole showed activities against CRAB, with resistant rates of 78.57% and 64.29%, respectively.
All CRKP strains were resistant to amoxicillin-clavulanate, ampicillin, ampicillin-sulbactam, and piperacillin-tazobactam. However, these strains showed low resistance to amikacin (14.52%) and gentamicin (20.97%). CRKP strains showed more than 80% resistance to the remaining tested antibiotics, except for cefuroxime axetil (41.94%), cefepime (45.16%), cefoxitin (41.94%), imipenem (75.81%), and trimethoprim-sulfamethoxazole (74.19%).
Phenotypic carbapenemase detection using MHT was performed on the 63 CRKP strains. A total of 30 out of 63 strains were MHT-positive, 26 were negative, and 7 strains were undetected. Among the MHT-negative strains, 14 harboured carbapenemase genes.

3. Discussion

Carbapenem-resistant organisms (CROs) have been a significant problem for healthcare institutions worldwide for over two decades. The increase in the number of CRO cases in our hospital is of concern. Among the 90 patients with CRAB in this study, 58.8% were admitted into the ICU. All were hospital-acquired, of which 54 (60%) were infections, with an inpatient mortality rate of 57.4%, whereas 36 (40%) were colonised, with an in-hospital mortality rate of 30.6%. In this institution, 134 CRAB cases were reported in the general ICU in 2015 and 2016, with a mortality rate of more than 50% [11]. Additionally, an outbreak of CRAB was recorded in the Neonatal Intensive Care Unit (NICU) between December 2016 and February 2017, leading to the death of three neonates [12]. CRAB often tends to affect debilitated patients, especially those with underlying health conditions or compromised immune systems, those with invasive devices, and those managed in the ICU [13]. This may be one of the main contributing factors to the high mortality rate of patients with CRAB.
Enzymatic inactivation, porin alteration, and the actions of the efflux pump are recognised as important mechanisms of carbapenem resistance in A. baumannii [7,14]. Nevertheless, the production of enzymes, including metallo-β-lactamases and oxacillinases, continues to be the most frequent and widespread resistance mechanism in CRAB. Metallo-β-lactamase genes (MBLs), including blaNDM, blaIMP, and blaVIM, were absent in our CRAB strains. blaIMP was found in CRAB strains in this hospital nearly ten years ago; however, it has not been reported in recent studies [11,15]. MBLs are less commonly identified in A. baumannii compared to OXA-type carbapenemase [16]. All CRAB strains in this study harboured at least one OXA-type carbapenemase gene, and 98% of them harboured dual carbapenemases, with blaOXA-23-like and blaOXA-51-like as predominant carbapenemase genes. The prevalence rates in this study are in concordance with most of the studies in Malaysia and other Asian and Southeast Asian countries [16,17,18,19]. OXA-type carbapenemases, which are class D β-lactamases, have been reported as the most widespread carbapenemase in A. baumannii, especially blaOXA-23-like [7,14]. blaOXA-23-like is mainly plasmid-encoded, which allows for horizontal transfer and facilitates the spread of this gene to different bacterial populations [20]. blaOXA-23-like was the first OXA-type carbapenemase identified from CRAB and remains the most prevalent worldwide today [16]. This gene has been implicated in numerous outbreaks of CRAB in healthcare settings, particularly in ICUs [21,22]. blaOXA-51-like genes are found to be naturally occurring in A. baumannii and are chromosomally located, which may explain their high prevalence [7]. Both blaOXA-23-like and blaOXA-51-like are the most prevalent carbapenemases in CRAB worldwide. The phylogenetic tree in this study (Figure 1) suggests that these genes are persistent within the healthcare setting and may serve as an ongoing source of transmission in HAI. Studies have shown that these organisms can survive on inanimate surfaces for months if environment cleaning is poor [23]. Thus, continuous surveillance and improvement in infection control measures are pivotal in healthcare facilities to manage and prevent outbreaks [12].
In contrast, the prevalence of blaOXA-58 is considered low as compared to blaOXA-23-like and blaOXA-51-like in CRAB in the Asian Pacific [24]. blaOXA-58 is mostly reported in the Western hemisphere, especially France, Spain, Italy, and the US, but rarely reported in Malaysia and other Asian countries [19,25]. Based on a previous study, blaOXA-58 was absent in our hospital settings in 2015 and 2016 [11]. In this study, the emergence of blaOXA-58 in our hospital is concerning and requires immediate attention, as this gene is plasmid-mediated [26] and has been associated with various HAIs and implicated in outbreaks [27]. Further, it represents a new challenge in the treatment and management of carbapenem-resistant infections. It is worth mentioning that the sequence type of CRAB strains harbouring blaOXA-58 is ST150 and ST643 and is different from the majority gene (blaOXA-23-like and blaOXA-51-like), which is mainly ST2. ST2 (77.5%) was our hospital’s dominant MLST type of CRAB. ST2 was the predominant sequence type of CRAB reported in Malaysia [19,28,29] and was also reported as the most prevalent sequence type of CRAB in Southeast Asia [30] and the United States [31]. A comparison between MLST profiles of all CRAB strains in this study showed low genetic diversity, with only seven sequence types detected among 90 CRAB strains. The presence of a dominant genotype among 77.5% of strains suggested the clonal spread of this pathogen in the hospital, emphasising the need to improve infection control measures.
Based on the 2022 National Antimicrobial Utilization Report, the use of broad-spectrum antibiotics is higher in teaching hospitals [9]. Once A. baumannii exhibits carbapenem resistance, it generally has acquired resistance to most other antibiotics, limiting its treatment options [32]. Furthermore, current treatment options and regimens are based on limited and conflicting data [33]. In resource-limited settings such as ours, where newer therapeutic options are not available, high-dose ampicillin-sulbactam in combination with polymyxin B is usually used [34,35]. It has been reported that a combination of polymyxin and ampicillin-sulbactam demonstrated high synergistic activity in vitro, especially in colistin-resistant strains [36]. However, the use of polymyxin is associated with an increased risk of nephrotoxicity [37]. The resistance rate of polymyxin B is also increasing, reported at 5.6% in 2022 [9]. The mortality rate associated with CRAB infections remains high (30.6%) even with appropriate polymyxin B treatment [38]. In this study, 3 out of 5 (60%) patients who received polymyxin B monotherapy and 15 out of 29 (51.7%) who received combination therapy died during hospitalisation.
Risk factors of mortality in patients with CRAB in this study include older age, Malay descent, the presence of a mechanical ventilator, and previous exposure to clindamycin. A total of 46.7% (n = 42) of patients died during their hospital stay. Infections with CRAB in healthcare settings are often seen in patients undergoing invasive procedures [35]. The contamination of mechanical ventilators has been reported as a source of outbreaks leading to high mortality [39,40]. Biofilm-forming A. baumannii contributes to its persistence in invasive devices and hospital environments [41]. The hydrophobic ability enables this organism to survive on abiotic surfaces and is hard to eliminate, even after four rounds of routine cleaning and disinfection [42]. Low immunity change in microbiota [43] may predispose older and ventilated patients to CRAB infection and an increased mortality rate. A specific link between ethnicity and CRAB infections was not established. Additionally, the small sample size in this study limits the ability to draw definitive conclusions about this factor. A further study on host genetic contributions to susceptibility to CRO infection is needed.
Interestingly, patients with prior exposure to clindamycin showed a lower risk of mortality in this study. Clindamycin, which is a lincosamide compound, is often used for anaerobic bacteria infection and has limited use as a single antimicrobial agent in A. baumannnii infections. A study of the activity of the efflux pump inhibitor phenylalanine-arginine β-naphthylamide (PaβN) against the AdeFGH pump of A. baumannii showed that PaβN had a greater inhibitory effect on the efflux of clindamycin compared to trimethoprim and chloramphenicol mediated by the AdeFGH efflux pump in A. baumannii [44]. Clindamycin can prevent the derepression of β-lactamases in certain bacterial strains without affecting the synthesis of other proteins or the bacterial replication process [45]. This suggests the potential of clindamycin as a unique therapeutic agent that not only directly targets bacterial growth but also disrupts the mechanisms of antibiotic resistance, particularly by inhibiting the induction of β-lactamase production. However, only a few patients had previous exposure to clindamycin in this study, and further analysis is required when more cases are included in the future.
In this study, 63 CRKP were collected, of which 47 were carbapenemase-producing CRKP (CP-CRKP), and 16 were non-carbapenemase-producing CRKP (NC-CRKP), with a mortality rate of 28.6%. Based on the trend in UMMC, the number of CRKP strains gradually increased from 17 strains in 2013 [46] to 115 strains in 2015 [47]. Importantly, there was an overall increase in CRKP, encompassing both CP-CRKP and NC-CRKP strains [48]. The only carbapenemase genes detected in this study are blaNDM (68.3%) and blaOXA-48-like (6.3%). Our previous studies suggest that the prevalence and persistence of blaNDM and blaOXA-48-like carbapenemase genes in our hospital setting have remained consistent over time [49]. However, the trend of CRKP has changed. Based on previous reports, the predominant carbapenemase gene in our hospital setting is the blaOXA-48-like gene [46,47,49]. Data suggested that blaNDM has replaced blaOXA-48-like as the predominant carbapenemase gene in CRKP strains in UMMC. This is not surprising as blaNDM predominates in Asia [50] and is leading cause of CRE in Malaysia [10]. Although NDM producers originated from the Indian subcontinent, their rapid dissemination worldwide, including Western Europe, North America, and the Far East, has been reported [8]. The increased prevalence of blaNDM among CRKP strains implied that the high transmissibility and plasticity of blaNDM-positive plasmids might have contributed substantially to its spread among existing bacterial populations in UMMC. IncL and IncFIIK plasmids carried by blaOXA-48 and blaNDM contributed to the conjugation and high plasmid stability of these genes [51]. Recently, the high prevalence of blaOXA-48 and blaNDM has been reported in Iran and Southern California [52,53,54]. This was similar to the carbapenemase trends observed in Malaysia. In this study, a K. pneumoniae strain carrying dual carbapenemase genes was identified, as previously reported [49]. Strains with dual carbapenemase genes are associated with higher levels of carbapenem resistance, which can lead to treatment complications and increased morbidity and mortality [55]. Other major carbapenemase genes, such as blaKPC, blaIMP, and blaVIM, have been reported in Malaysia but were absent in this study [46,47,56]. blaKPC was mainly reported in North America and slowly disseminated to other European countries but still remains less prevalent in Asian continents, whereas blaVIM was frequently isolated in Mediterranean countries. blaIMP was primarily described in Japan; however, the dissemination of IMP-producing K. pneumoniae in the rest of the world appears to be limited [8].
MLST analysis revealed that 34 sequence types were detected among 63 CRKP strains, indicating greater diversity in CRKP compared to CRAB strains. ST20 (16.13%) was the most prevalent ST in CRKP strains in this study, which is in contrast to 2017, where the predominant ST in our hospital was ST101 [46]. This demonstrates that the genomic patterns of CRKP can be highly diverse and dynamic, even within the same hospital setting. MLST analysis revealed genetic diversity among the CRKP strains, highlighting their complex and heterogeneous nature. This diversity indicates that multiple different lineages of K. pneumoniae are circulating and contributing to carbapenem resistance within the hospital and likely arising from multiple independent sources circulating within the hospital rather than from a single clonal outbreak.
Based on the previous report, the in-hospital mortality rate of CRKP in 2013, 2014, 2015, and 2016 to 2017 was 35.3%, 27.3%, 42.6%, and 43.4%, respectively [46,47,49]. In this study, the rate was higher at 73%. However, this may be an overestimation and may not reflect the annual mortality rate. Nevertheless, one of the main reasons for the high mortality of CRKP in this region is the limited effective treatment options. The first-line therapy that is mostly used in resource-limited settings is polymyxin combination therapy, which has been shown to be significantly inferior to newer β-lactam/β-lactamase inhibitor (BLBI) combinations, like ceftazidime-avibactam (CAZ/AVI) and meropenem-vaborbactam, in randomised controlled trials [57]. Unfortunately, many of these trials have focused on KPC-producing CRE, and their efficacy against metallo-β-lactamase (MBL)-producing strains like NDM is limited, necessitating the exploration of other combination therapies. In a prospective study by Falcone et al., the mortality rate was significantly lower when using a combination of ceftazidime-avibactam (CAZ/AVI) with aztreonam (9.2%) compared to polymyxin-based combination therapy (44%) for treating NDM-producing Enterobacterales [58]. However, the ability of these antibiotics in resource-limited settings is often limited due to high costs, a lack of approval, or restricted access.
Older age, male, ICU admission, and indwelling urinary catheters are significantly associated with an increased risk of mortality. Patients who were admitted to the ICU have more severe illnesses, numerous comorbidities, and invasive devices; are often immunocompromised; and have a greater susceptibility to infections. Therefore, they are exposed to more antibiotics [59]. Frequent invasive procedures and indwelling tubes can damage the mucosal barrier, leading to a further increased risk of CRKP exogenous and endogenous infection [60]. CRKP can form biofilms on the surfaces of indwelling devices, making the infection more difficult to treat and more persistent, leading to a higher risk of in-hospital mortality [61].
The limitation of the current study is the limited number of selected CROs from a teaching hospital due to limited resources. Hence, not all CROs are included; the small sample size may include potential bias and lead to deviation in statistical analysis. This study could only represent the current assessment of CRAB and CRKP in our hospital at the present time. In this study, several confounders, such as polymicrobial infections and other underlying diseases, might affect the risk factor of in-hospital mortality analysis.

4. Materials and Methods

4.1. Ethics Statement

The medical ethics approval was obtained from the Universiti Malaya Medical Centre Medical Ethics Committee before extracting clinical data from the hospital database (MREC No: 2020117-8191).

4.2. Bacterial Strain Collection and Hospital Setting

This retrospective study was conducted at the Universiti Malaya Medical Centre (UMMC), a 1600-bed tertiary public teaching hospital in Kuala Lumpur, Malaysia, from May 2019 to December 2020. In 2019, there were 155 reported cases of CRAB and 66 of CRE. In 2020, the reported cases increased to 161 for CRAB and 140 for CRE. Approximately 30% of the strains from both years, including 90 CRAB and 63 CRKP, were randomly selected. The selected strains were revived from the collection in the microbiology laboratory and were included for analysis in this study. CRAB and CRKP that exhibited resistance or intermediate resistance to at least one carbapenem (imipenem, meropenem or ertapenem), as determined by Clinical and Laboratory Standards Institute (CLSI) 2017 guidelines, were included in this study [62]. The strains were collected from various samples, including swabs, sputum, tracheal secretions, bronchoalveolar lavage, urine, blood, and tissue. All bacterial strains were revived from glycerol stock culture and checked for purity before the commencement of benchwork. Crude DNA was extracted by using the direct boiling method [49].

4.3. Detection of Carbapenemase Genes

The presence of carbapenemase genes in CRAB, which included blaOXA [63], blaIMP [64], blaVIM [65], and blaNDM [66], and carbapenemase genes in CRKP such as blaKPC [67], blaOXA-48-like [68], blaIMP, blaVIM, and blaNDM [69], were detected by using polymerase chain reaction (PCR) with specific primers and cycling parameters, as previously described. The amplicon was then analysed using 1.0% agarose gel.

4.4. Clonal Relatedness of Strains

Multi-locus sequence typing (MLST) was performed on CRAB and CRKP strains by using Pasteur Institute scheme (http://pubmlst.org/abaumannii/, accessed on 14 February 2023 and http://www.pasteur.fr/mlst/, accessed on 15 February 2023) [70,71,72]. Seven housekeeping genes for each species (CRAB: cpn60, fusA, gltA, pyrG, recA, rplB, rpoB; CRKP: gapA, infB, mdh, pgi, phoE, rpoB, tonB) were amplified and sequenced to determine the sequence types and clonal relatedness among strains. Phylogenetic trees were constructed with the maximum likelihood method by using MEGA software version 10.1.7 [73]. The differences in allelic profiles were determined by using the BURST plugin with BIGSdb database software in PubMLST (https://pubmlst.org/software/bigsdb, accessed on 12 January 2024) [70]. Allelic profiles that differ from one another at one of the seven MLST loci are called single-locus variants (SLVs), two of the seven loci are called double-locus variants (DLVs), and three of the seven loci are called triple-locus variants (TLVs) [74]. STs that cannot be assigned to any groups are defined as singletons. A minimum spanning tree (MST) was created with the goeBURST algorithm in PHYLOViS 2.0 software to identify the clonal complexes (CC) [74,75]. Untypeable strains were removed from the analysis.

4.5. Antimicrobial Susceptibility Testing and Modified Hodge Test

Bacterial identification and antimicrobial susceptibility testing (AST) were performed by an automated system (Vitek® 2; BioMérieux, Marcy L’Etoile, France). A total of 13 antibiotics were tested for CRAB strains, including amikacin (AN), ceftazidime (CAZ), ciprofloxacin (CIP), ceftriaxone (CRO), cefotaxime (CTX), ertapenem (ETP), cefepime (FEP), gentamicin (GM), imipenem (IPM), meropenem (MEM), ampicillin-sulbactam (SAM), trimethoprim-sulfamethoxazole (SXT), and piperacillin-tazobactam (TZP). In contrast, five additional antibiotics, which consist of amoxicillin-clavulanate (AMC), ampicillin (AMP), cefuroxime (CXM), cefuroxime axetil (CXMA), and cefoxitin (FOX), were tested for CRKP strains. AST was determined by using the AST-N314 card (BioMérieux, Marcy L’Etoile, France) under the Vitek 2 system. Susceptibility breakpoints were interpreted based on the recommendations of the CLSI 2017 (http://www.clsi.org/). Colistin susceptibility test was not included because broth microdilution was the only recommended testing standard for colistin by CLSI and the European Committee on Antimicrobial Susceptibility Testing (EUCAST).
The detection of carbapenemase production in K. pneumoniae was carried out using the Modified Hodge Test (MHT), with K. pneumoniae ATCC BAA-1705 and K. pneumoniae ATCC BAA-1706 being utilised as MHT-positive and -negative controls, respectively, according to CLSI guideline [62].

4.6. Clinical Data Collection and Statistical Analysis

All patients’ data were retrieved from the electrical medical record (EMR), including patient demographics, length of hospital stay, isolation date, sample sources, previous hospitalisation, intensive care unit (ICU) admission, presence of invasive device, comorbidity, antimicrobial exposure within 90 days of CROs isolation, empirical treatment, definitive treatment, and treatment outcome. An empiric antibiotic is defined as the initial antibiotic treatment given within 48 h of obtaining culture, prior to the availability of microbiological results. The empiric antibiotic was deemed appropriate if its spectrum included coverage for CRAB or CRKP [76,77]. Definitive treatment is defined as antibiotics administered to the patient based on the microbiological susceptibility results once they are available [77]. Patients were classified as having an infection when clinical and biochemical evidence of infection was present, while patients who exhibited no signs or symptoms were categorised as colonisation [78]. The location of acquisition of CROs is categorised as follows: (1) Hospital-acquired infection (HAI), which is defined as the isolation of a microorganism from patients more than 48 h after hospitalisation who did not show any signs or symptoms during admission [79]. (2) Community-acquired infection (CAI), which is defined as the isolation of microorganisms from patients less than 48 h after admission who showed symptoms and did not come into contact with healthcare facilities in the past 3 months [79]. (3) Healthcare-associated infection (HCAI), which refers to the isolation of microorganisms from patients less than 48 h after admission who had contact with healthcare in the previous three months [79,80]. (4) Colonisation (HAC) is defined as the isolation of microorganisms from any non-sterile body site with the absence of clinical findings of infection [81].
Risk factors associated with in-hospital mortality were first compared using IBM SPSS™ Statistic software (New York, NY, USA), version 28. A chi-square test or Fisher’s exact test was performed for categorical variables. In contrast, continuous variables were analysed using either the Mann–Whitney U test or Student’s t-test based on data normality. All statistical analysis was further conducted in R version 4.2.2. Completed clinical data for 90 CRAB and 63 CRKP strains were included in the analysis. A collinearity test was carried out to test the reliability of regression coefficients. Logistic regression analysis using the ‘glmer()’ function was conducted in R to determine the risk factors associated with in-hospital mortality with CROs. Empiric and definitive treatments were analysed with infected patients only. Variables with a p value less than 0.1 were selected for inclusion in multivariate logistic regression analysis, which run in the build model in the R package. ‘Dredge’ command was implemented in the R MuMIn package to identify the parsimonious model.

5. Conclusions

In conclusion, OXA-type carbapenemase genes were the only carbapenemases detected in CRAB strains in this study. blaOXA-58, which is rare in local findings, was detected in this study. In contrast, the trend of CRKP strains in this hospital changed from blaOXA-48 into the blaNDM carbapenemase gene. The dominant sequence types of CRAB and CRKP are ST2 and ST20, respectively. The squence type of CRKP is more diverse than CRAB in this study. Early detection, effective preventive measures, and the development of novel agents with reliable clinical efficacy are crucial in addressing the spread of CROs. The findings in this study may assist support the prevalence and epidemiology data of CROs in the hospital in Malaysia. The identification of carbapenem-resistant genes assisted in selecting appropriate antibiotic treatment and guiding future interventions and infection control of CROs in Malaysia.

Author Contributions

Conceptualisation, C.S.J.T. and S.P.; methodology, C.S.J.T. and M.Y.L.; software, C.W.C. and J.D; validation, C.S.J.T., C.W.C. and S.P.; formal analysis, C.W.C. and J.D.; investigation, C.S.J.T.; resources, S.P.; data curation, C.W.C.; writing—original draft preparation, M.Y.L.; writing—review and editing, Y.Q.L., J.J.W. and Z.X.K.; visualisation, A.S.J., Y.Q.L., J.J.W. and Z.X.K.; supervision, C.S.J.T., S.P. and U.H.O.; project administration, C.S.J.T. and M.Y.L. funding acquisition, A.S.J., C.W.C., M.C.C.L., U.H.O. and C.S.J.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Ministry of Higher Education (Malaysia), Transdisciplinary Research Grant Scheme TRGS (TRGS/1/2020/UM/02/2/2), grant number TR001B-2020, and the MRUN Young Researchers Grant Scheme, grant number MR002-2019.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

The study conducted was approved by UMMC Medical Ethics Committee (MREC ID: 2020117-8191) to conduct research on clinical isolates and to access clinical data.

Data Availability Statement

Data are contained within the article.

Acknowledgments

We thank the University of Malaya for its support and facilities.

Conflicts of Interest

The authors declare no conflicts of interest.

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Antibiotics 13 01107 g001
Figure 1. Phylogenetic tree of CRAB isolates.
Figure 1. Phylogenetic tree of CRAB isolates.
Antibiotics 13 01107 g001
Antibiotics 13 01107 g002
Figure 2. Phylogenetic tree of CRKP isolates. NO: No carbapenemase genes.
Figure 2. Phylogenetic tree of CRKP isolates. NO: No carbapenemase genes.
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Antibiotics 13 01107 g003
Figure 3. (a) Minimum spanning trees of CRAB strains. The ST prefix is not shown (i.e., 2 corresponds to ST2). (b) Minimum spanning tree of CRKP strains. The ST prefix is not shown (i.e., 20 corresponds to ST20).
Figure 3. (a) Minimum spanning trees of CRAB strains. The ST prefix is not shown (i.e., 2 corresponds to ST2). (b) Minimum spanning tree of CRKP strains. The ST prefix is not shown (i.e., 20 corresponds to ST20).
Antibiotics 13 01107 g003
Table 1. Risk factors for in-hospital mortality for patients with CRAB and CRKP isolation.
Table 1. Risk factors for in-hospital mortality for patients with CRAB and CRKP isolation.
Risk FactorsIn-Hospital Mortality CRABChi Square (p Value)In-Hospital Mortality CRKPChi Square (p Value)
No (n = 48)Yes (n = 42)No (n = 45)Yes (n = 18)
Gender 1 0.027 *
Female16 (53.3%)14 (46.7%) 21 (87.5%)3 (22.5%)
Male32 (53.3%)28 (46.7%) 24 (61.5%)15 (38.5%)
Ethnic 0.106 0.645
Malay9 (37.5%)15 (62.5%) 16 (64.0%)9 (36.0%)
Chinese16 (61.5%)10 (39.5%) 17 (81.0%)4 (19.0%)
India17 (51.5%)16 (48.5%) 9 (69.2%)4 (30.8%)
Others6 (85.7%)1 (14.3%) 3 (75.0%)1 (25.0%)
ICU admission26 (49.1%)27 (50.9%)0.33031 (64.6%)17 (35.4%)0.047 *a
Infection acquire model 0.021 * 0.292
CAI0 (0%)0 (0%) 0 (0%)0 (0%)
HAI23 (44.2%)29 (55.8%) 8 (57.1%)6 (42.9%)
HAC25 (69.4%)11 (30.6%) 36 (76.6%)11 (23.4%)
HCAI0 (0%)2 (100%) 1 (50%)1 (50%)
Invasive device
Indwelling urinary catheter41 (50.6%)40 (49.4%)0.166 a32 (65.3%)17 (34.7%)0.051 a
Mechanical ventilator33 (47.1%)37 (52.9%)0.028 *32 (64.0%)18 (36.0%)0.013 *a
Tracheostomy13 (54.2%)11 (45.8%)0.92410 (71.4%)4 (28.6%)1.000 a
Central veneous catheter35 (49.3%)36 (50.7%)0.13826 (59.1%)18 (40.9%)<0.001 *a
Art line26 (49.1%)27 (50.9%)0.33028 (65.1%)15 (34.9%)0.104
Peripheral veneous line40 (52.6%)36 (47.4%)0.75640 (71.4%)16 (28.6%)1.000
NG tube36 (50.0%)36 (50.0%)0.20527 (60.0%)18 (40.0%)0.001 *a
Stoma4 (57.1%)3 (42.9%)1.000 a4 (80.0%)1 (20.0%)1.000 a
Specimen sources 0.048 * 0.197
Respiratory30 (46.2%)35 (53.8%) 7 (77.8%)2 (22.2%)
Urinary2 (100%)0 (0%) 4 (100%)0 (0%)
Blood1 (25.0%)3 (75.0%) 5 (83.3%)1 (16.7%)
Skin and soft tissue14 (77.8%)4 (22.2%) 5 (100%)0 (0%)
Rectal swabs0 (0%)0 (0%) 23 (63.9%)13 (36.1%)
Others1 (100%)0 (0%) 1 (33.3%)2 (66.7%)
Previous hospitalisation
>1 year2 (100%)0 (0%)0.497 a2 (66.7%)1 (33.3%)1.000 a
6–12 months5 (55.6%)4 (44.4%)1.000 a4 (100%)0 (0%)0.317 a
3–6 months2 (33.3%)4 (66.7%)0.412 a4 (100%)0 (0%)0.317 a
<3 months26 (61.9%)16 (38.1%)0.12727 (71.1%)11 (28.9%)0.935
none13 (48.1%)14 (51.9%)0.5198 (61.5%)5 (38.5%)0.492 a
Previous contact to health care facilities29 (53.7%)25 (46.3%)0.93134 (72.3%)13 (27.7%)0.760 a
Comorbidity
CKD19 (45.2%)23 (54.8%)0.15023 (67.6%)11 (32.4%)0.472
DM22 (47.8%)24 (52.2%)0.28419 (61.3%)12 (38.7%)0.080
CVD8 (36.4%)14 (63.6%)0.0669 (56.3%)7 (43.8%)0.198 a
Malignancy14 (63.6%)8 (36.4%)0.2657 (100%)0 (0%)0.177 a
HPT20 (46.5%)23 (53.5%)0.21524 (64.9%)13 (35.1%)0.169
Previous antibiotic exposure in last 90 days48 (54.5%)40 (45.5%)0.215 a43 (70.5%)18 (29.5%)1.000 a
Conventional Penicillin8 (72.7%)3 (27.3%)0.1693 (75.0%)1 (25.0%)1.000 a
Cloaxacillin5 (55.6%)4 (44.4%)1.000 a9 (81.8%)2 (18.2%)0.489 a
Augmentin/Unasyn17 (44.7%)21 (55.3%)0.16220 (76.9%)6 (23.1%)0.418
Piperacillin-tazobactam31 (52.5%)28 (47.5%)0.83622 (66.7%)11 (33.3%)0.380
Aminoglycoside6 (60.0%)4 (40%)0.745 a3 (75.0%)1 (25.0%)1.000 a
Vancomycin23 (60.5%)15 (39.5%)0.2429 (52.9%)8 (47.1%)0.063 a
1st-generation cephalosporin0 (0%)1 (100%)0.467 a4 (100%)0 (0%)0.317 a
2nd-generation cephalosporin9 (56.3%)7 (43.7%)0.7967 (87.5%)1 (12.5%)0.421 a
3rd-generation cephalosporin17 (63.0%)10 (37.0%)0.23116 (72.7%)6 (27.3%)0.867
4th-generation cephalosporin5 (50.0%)5 (50.0%)1.000 a6 (60.0%)4 (40.0%)0.452 a
5th-generation cephalosporin1 (100%)0 (0%)1.000 a---
Clindamycin8 (88.9%)1 (11.1%)0.033 a2 (100%)0 (0%)1.000 a
Metronidazole10 (55.6%)8 (44.4%)0.8335 (71.4%)2 (28.6%)1.000 a
Polymyxin B1 (20.0%)4 (80.0%)0.181 a4 (66.7%)2 (33.3%)1.000 a
Meropenem20 (44.4%)25 (55.6%)0.09121 (72.4%)8 (27.6%)0.873
Macrolides6 (46.2%)7 (53.8%)0.5757 (100%)0 (0%)0.177 a
Fluoroquinolones2 (40.0%)3 (60.0%)0.661 a2 (100%)0 (0%)1.000 a
Bactrim2 (40.0%)3 (60.0%)0.661 a2 (50.0%)2 (50.0%)0.571 a
Monoinfection6 (40.0%)9 (60.0%)0.25710 (76.9%)3 (23.1%)0.741 a
Carbapenemase genes
OXA-2347 (53.4%)41 (46.6%)1.000 a---
OXA-5147 (52.8%)42 (47.2%)1.000 a---
OXA-581 (50.0%)1 (50.0)1.000 a---
OXA-48 3 (75.0%)1 (25.0%)1.000 a
NDM 31 (72.1%)12 (27.9%)0.864
No carbapenemase 12 (75.0%)4 (25.0%)1.000 a
Empiric antibiotics
(Patients received treatmemt: CRAB = 47; CRKP = 15)		21 (44.7%)26 (55.3%)0.685 a9 (60.0%)6 (40.0%)0.438 a
Appropriate treatment (CRAB = 3; CRKP = 3)1 (33.3%)2 (66.7%)1.000 a1 (33.3%)2 (66.7%)0.525 a
Polymyxin B monotherapy1 (50.0%)1 (50.0%)1.000 a---
Polymyxin B and Meropenem therapy0 (0.0%)1 (100.0%)1.000 a1 (100.0%)0 (0.0%)1.000 a
Meropenem---0 (0.0%)2 (100.0%)0.143 a
Inappropriate treatment20 (45.5%)24 (54.5%)1.000 a8 (66.7%)4 (33.3%)0.525 a
Definitive Treatment
(Patients received treatment: CRAB = 40; CRKP = 14)		19 (47.5%)21 (52.5%)0.2189 (64.3%)5 (35.7%)0.175 a
Appropriate treatment (CRAB = 36; CRKP = 10)18 (50.0%)18 (50.0%)0.607 a6 (60.0%)4 (40.0%)1.000 a
Polymyxin B monotherapy2 (40.0%)3 (60.0%)1.000 a1 (100.0%)0 (0.0%)1.000 a
Polymyxin B and Unasyn therapy10 (43.5%)8 (44.4%)0.356---
Polymyxin B and Meropenem therapy2 (22.2%)7 (77.8%)0.133 a5 (62.5%)3 (37.5%)1.000 a
Polymyxin B and other therapy2 (100.0%)0 (0.0%)0.219 a---
Ciprofloxacin1 (100.0%)0 (0.0%)0.475 a---
Ceftazidime1 (100.0%)0 (0.0%)0.475 a---
Meropenem---0 (0.0%)1 (100.0%)1.000 a
Inappropriate treatment1 (25.0%)3 (75.0%)0.607 a3 (75.0%)1 (25.0%)1.000 a
* p < 0.05. a p value obtained using Fisher’s exact test. CKD: chronic kidney disease; DM: diabetes mellitus; CVD: cardiovascular disease; HPT: hypertension.
Table 2. Logistic regression analysis for mortality associated with CRAB and CRKP infection.
Table 2. Logistic regression analysis for mortality associated with CRAB and CRKP infection.
Risk FactorsCRAB (Total Infected Patients = 54)Odd Ratio (95% CI)CRKP (Total Infected Patients = 16)Odd Ratio (95% CI)
Univariate AnalysisMultivariate AnalysisUnivariate AnalysisMultivariate Analysis
Gender1.000 0.0270.073 [0.015]3.86 (0.88–16.93) [8.75 (1.53–50.11)]
Age0.0200.0260.10 (0.01–0.76)0.0360.0881.04 (0.99–1.08)
Ethnic0.0830.0620.60 (0.35–1.03)0.582
ICU admission0.336 0.0320.1605.10 (0.52–49.59)
Infection acquire model0.155 0.356
Invasive device
Indwelling urinary catheter		0.124 0.0450.1215.48 (0.57–52.77)
Mechanical ventilator0.0280.0075.16 (1.56–17.09)0.001[0.997][5.92 (0–Inf)]
Tracheostomy0.925 1.000
Central veneous catheter0.141 0.001[0.997][4.80 (0–Inf)]
Art line0.335 0.107
Peripheral veneous line0.759 1.000
NG tube0.209 0.001[0.996]6.71 [(0–Inf)]
Stoma0.835 0.665
Previous hospitalisation
<3 months0.130 0.936
none0.524 0.384
Previous contact to health care facilities0.932 0.788
Comorbidity
CKD0.153 0.480
DM0.290 0.082
CVD0.068 0.124
Malignancy0.270 0.078[0.997][5.92 (0–Inf)]
HPT0.219 0.174
Dyslipidemia- 0.185
Previous antibiotic exposure in last 90 days
Conventional Penicillin0.173 -
Cloaxacillin0.890 0.409
Augmentin/Unasyn0.170 0.427
Piperacillin-tazobactam0.838 0.388
Aminoglycoside0.658 -
Vancomycin0.247 0.049
2nd-generation cephalosporin0.799 0.289
3rd-generation cephalosporin0.235 0.870
4th-generation cephalosporin0.825 0.391
Clindamycin0.0240.0160.07 (0.007–0.60)-
Metronidazole0.835 1.000
Polymyxin B- 0.790
Meropenem0.093 0.875
Macrolides0.580 0.078[0.998][3.89 (0–Inf)]
Monoinfection0.262 0.629
Carbapenemase genes
OXA-230.925 -
OXA-510.352 -
OXA-580.925 -
OXA-48- 0.873
NDM- 0.867
No carbapenemase- 0.930
Empiric antibiotics
(Total infected patients: CRAB = 54; CRKP = 16)
Appropriate treatment0.380 0.133
Definitive Treatment
(Total infected patients: CRAB = 54; CRKP = 16)
Appropriate treatment0.535 0.131
Polymyxin B monotherapy0.180 0.396
Polymyxin B and Unasyn therapy0.382 -
Polymyxin B and Meropenem therapy0.744 0.642
Polymyxin B and other therapy0.833 -
Remarks: values in brankets [] indicate results before excluding high-probability variables. CKD: chronic kidney disease; DM: diabetes mellitus; CVD: cardiovascular disease; HPT: hypertension; Inf: infinity.
Table 3. Antimicrobial susceptibility profile for CRAB and CRKP strains.
Table 3. Antimicrobial susceptibility profile for CRAB and CRKP strains.
AntibioticsCRAB (n = 84)CRKP (n = 62)
Amoxicillin-clavulanate (AMC)-62 (100.00%)
Ampicillin (AMP)-62 (100.00%)
Amikacin (AN)70 (83.33%)9 (14.52%)
Ceftazidime (CAZ)82 (97.62%)61 (98.39%)
Ciprofloxacin (CIP)75 (89.29%)51 (82.26%)
Ceftriaxone (CRO)82 (97.62%)61 (98.39%)
Cefotaxime (CTX)83 (98.81%)61 (98.39%)
Cefuroxime (CXM)-61 (98.39%)
Cefuroxime Axetil (CXMA)-26 (41.94%)
Ertapenem (ETP)66 (78.57%)59 (95.16%)
Cefepime (FEP)84 (100.00%)28 (45.16%)
Cefoxitin (FOX)-26 (41.94%)
Gentamicin (GM)71 (84.52%)13 (20.97%)
Imipenem (IPM)84 (100.00%)47 (75.81%)
Meropenem (MEM)84 (100.00%)50 (80.65%)
Ampicillin-sulbactam (SAM)84 (100.00%)62 (100.00%)
Trimethoprim-sulfamethoxazole (SXT)54 (64.29%)46 (74.19%)
Piperacillin-tazobactam (TZP)84 (100.00%)62 (100.00%)
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Lau, M.Y.; Ponnampalavanar, S.; Chong, C.W.; Dwiyanto, J.; Lee, Y.Q.; Woon, J.J.; Kong, Z.X.; Jasni, A.S.; Lee, M.C.C.; Obaidellah, U.H.; et al. The Characterisation of Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in a Teaching Hospital in Malaysia. Antibiotics 2024, 13, 1107. https://doi.org/10.3390/antibiotics13111107

AMA Style

Lau MY, Ponnampalavanar S, Chong CW, Dwiyanto J, Lee YQ, Woon JJ, Kong ZX, Jasni AS, Lee MCC, Obaidellah UH, et al. The Characterisation of Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in a Teaching Hospital in Malaysia. Antibiotics. 2024; 13(11):1107. https://doi.org/10.3390/antibiotics13111107

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Lau, Min Yi, Sasheela Ponnampalavanar, Chun Wie Chong, Jacky Dwiyanto, Yee Qing Lee, Jia Jie Woon, Zhi Xian Kong, Azmiza Syawani Jasni, Michelle Chin Chin Lee, Unaizah Hanum Obaidellah, and et al. 2024. "The Characterisation of Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in a Teaching Hospital in Malaysia" Antibiotics 13, no. 11: 1107. https://doi.org/10.3390/antibiotics13111107

APA Style

Lau, M. Y., Ponnampalavanar, S., Chong, C. W., Dwiyanto, J., Lee, Y. Q., Woon, J. J., Kong, Z. X., Jasni, A. S., Lee, M. C. C., Obaidellah, U. H., & Teh, C. S. J. (2024). The Characterisation of Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae in a Teaching Hospital in Malaysia. Antibiotics, 13(11), 1107. https://doi.org/10.3390/antibiotics13111107

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