Antimicrobial Resistance
Antimicrobial Resistance
Antimicrobial Resistance
Nashreeyn Mohamed Naeemmudeen, MSc1, Nur Ainaa Nabihah Mohd Ghazali, MSc1, Hasnah Bahari, PhD2,
Rosni Ibrahim, MPath1, Ahmad Dzulfikar Samsudin, MClinDent3, Azmiza Syawani Jasni, PhD1
1
Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang,
Selangor, Malaysia, 2Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM
Serdang, Selangor, Malaysia, 3Department of Oral and Maxillofacial Surgery, Pathology and Medicine, Faculty of Dentistry,
Universiti Sains Islam Malaysia, Ampang, Selangor, Malaysia
ABSTRACT
Introduction: Antibiotic resistance is a burgeoning problem
which were obtained from various studies, as well as the
published in English were considered. The World Health Organization (WHO) has come up with a
KEYWORDS:
highlights the urgency of an action plan to combat the issue
comprehensively.
Antimicrobial resistance, Malaysian action plan, antibiotic-
resistant bacteria Prevalence of Antibiotic-Resistant Bacteria in Malaysia
Escherichia coli
INTRODUCTION
The urinary tract infections caused by Escherichia coli (E. coli)
is the most common bacterial infection in patients
Antimicrobial resistance arises as microorganisms survive worldwide7 and its occurrence is estimated to be up to 88.0%.8
and reproduce when exposed to antimicrobial drugs. Back in Malaysia is one of the countries with higher E. coli resistance
1907, Paul Ehrlich, the father of modern chemotherapy towards aminopenicillin.9 Data from various public hospitals
observed that the organism in trypanosome infections in Malaysia revealed that the majority of the tested E. coli
sometimes appears to be resistant to the agent used. Due to isolates showed the highest resistance rate to penicillins
specific resistance, he observed that fuchsin dye-resistant ranging from 68-100% (Table I). This resistance pattern
strain was still susceptible to an arsenic compound, while a remains for years and in fact, some of the isolates were also
strain resistant to the arsenic compound retained sensitivity resistant to two or more antibiotics (multidrug-resistant).10
to the dye. Later in 1908, he proposed that the resistance can Data also showed that from the year 2004 to 2018, the
be steadily inherited once it is acquired.1 resistance of E. coli to carbapenems remains low within the
range of 0-5%, with a steady increment reported over the
This review provides a general overview of the antimicrobial years.11-16
resistance trends of selected clinical isolates in Malaysia
Additionally, an imipenem-resistant E. coli was reported mecA gene.27 One of the earliest reports from Hospital Kuala
between 2006 and 2009 and were among the first resistant Lumpur (HKL) recorded all 539 MRSA isolates were resistant
isolates reported in the country.12 Resistance rates of more to penicillin.28 The resistance rates remained constant until
than 85% for ciprofloxacin and cefuroxime were also 2018 with 100% isolates were resistant (Table IV). Likewise,
reported between 2017 and 2018.15 The data presented the resistance rates to gentamicin persisted over the years
showed that E. coli is resistant to antibiotic groups that have with the highest rates reported between 1990-1991 and 2002-
been widely used for the longest time, although some 2007.28,29 Resistance to erythromycin showed a steady declined
fluctuations were observed which is due to the number of over the years, while the isolates showed an increase in
isolates tested in the individual hospitals. Many studies have resistance patterns to clindamycin, from 0% in 2006-2007 to
suggested that the intrinsic resistance and the expression of an average of 83% in 2011-2013.30-32 Until 2018, none of the
numerous efflux pumps could be the major contributors to S. aureus isolates is resistant to linezolid or vancomycin.28-33
the resistance patterns observed in this organism.
Enterococcus sp.
Acinetobacter baumannii Enterococcus sp. are part of the normal flora and are natural
Acinetobacter baumannii (A. baumannii) is an opportunistic inhabitants of nature. They are also opportunistic pathogens
pathogen that can easily acquire resistance elements such as that can pose serious threats to human life. Treatment for
plasmids and conjugative transposons.17 The broad-spectrum enterococci infections is challenging as they are intrinsically
carbapenems are the antibiotic of choice for complications resistant to multidrug and can develop resistance to other
associated with A. baumannii although the resistance rate has classes of antibiotics. From the year 2007 to 2008,
been increasing in the last two decades. Enterococcus faecium (E. faecium) isolates showed complete
resistance to vancomycin, ampicillin, and teicoplanin.34
A report by University Malaya Medical Centre (UMMC) Although ampicillin-resistant Enterocccus faecalis (E. faecalis)
between 1996 and 1998 showed a 100% carbapenems- was also reported, the rates were much lesser than the ones
resistant Acinetobacter baumannii (CRAB) resistance towards reported in E. faecium.13,35-36
amoxicillin-clavulanate, ampicillin, cefoperazone, and
cefuroxime. Additionally, more than 90% resistance was Despite that 100% vancomycin-resistant E. faecium was
observed for cephalosporins, gentamicin, and ciprofloxacin.18 reported between 2007-2008, the rates fall to 14.1% in 2018.
Over the years, the resistance rates for penicillins showed a Unlike E. faecium, the number of vancomycin-resistant E.
decrement up to 50%.13,16,19-23 faecalis isolates were very less, with the highest rate of 6%
reported over the years.13,35-36 The resistance rates for
The resistance rates for cephalosporins do not show gentamicin and linezolid were reasonably constant over the
substantial change, although in 2018 for the first time in years for both E. faecium and E. faecalis isolates.13,16,34-36
several years, the resistance rate plummeted to 37.9% (Table Conversely, the resistance rates of erythromycin and
II). Conversely, the resistance rates to carbapenems and tetracycline among the enterococci isolates were high with an
aminoglycosides fluctuated with the highest rates reported average of 98% (Table V).36
between 2017 and 2018. The data also showed an increasing
trend of resistance to fluoroquinolones with an average of The Contributing Factors
93% in the last two years.16,23 According to WHO, misuse and overuse of antimicrobial
agents are the main causes of antibiotic resistance.4 As of
Klebsiella pneumoniae 2016, the National Medical Care Survey (NMCS) has
Klebsiella sp. are a reservoir for antibiotic-resistant genes and gathered data of 27,587 patients from 545 healthcare clinics
can transfer the gene to other Gram-negative bacteria. and 5810 (21.1%) patients that received antibiotic
Studies on Klebsiella pneumoniae (K. pneumoniae) infections prescriptions through which 197 (3.4%) of them were
and antibiotic resistance in Malaysia are scanty. Between prescribed with more than one antibiotic.37
2010 and 2012, the majority of the K. pneumoniae isolates
tested were resistant to second and third generations Another observation revealed that the rate of antibiotic
cephalosporins (97-100%).24,25 As shown in Table III, the prescriptions in private clinics (30.8%) is higher than in
ampicillin, amoxicillin-clavulanate acid and aztreonam public or government clinics (6.8%). Almost half of the
resistances were high among K. pneumoniae species with an prescribed antibiotics are for acute upper respiratory tract
average of 94-100%.25 The trends plunged drastically in 2013 infections (URTI) followed by other diagnoses such as fever
and 2017 13 with the lowest resistance rates recorded that is and gastroenteritis.
possibly due to the significant number of isolates tested as
compared to the earlier years. The resistance rate to Consumption of foods contaminated with pathogenic E. coli
gentamicin was recorded between 2010 and 2017, with the may lead to bacterial infections and many studies on E. coli
lowest resistance rate recorded in 2017 (8.5%).13 Data also are concerned with beef samples. A study isolated 55 E. coli
revealed a steady increase in the resistance pattern to strains from ducks in Penang and showed that they are
carbapenems.13 completely resistant to vancomycin and more than 60% are
resistant to tetracycline, ampicillin, and streptomycin.38
Staphylococcus aureus Another study reported that out of 40 beef samples taken
Staphylococcus aureus (S. aureus) possesses the ability to from two local abattoirs in Selangor contains
700
Year Type of Antibiotics Source*
Ampicillin %
Piperacillin %
Amoxicillin %
Cefuroxime %
Ceftazidime %
Cefepime %
Imipenem %
Meropenem %
Amikacin %
Gentamicin %
Ciprofloxacin %
Trimethoprim-
sulfamethoxazole %
2004 77 64 17 6 0 2 21 33 10
(47) (47) (47) (47) (47) (47) (47) (47)
Systematic / Narrative Review Article
Amoxicillin-
Clavulanate %
Ampicillin %
Piperacillin %
Cefoperazone %
Cefuroxime %
Ceftazidime %
Ceftriaxone %
Cefotaxime %
Imipenem %
Ciprofloxacin%
Amikacin %
Gentamicin %
Netilmicin %
Colistin %
1996-1998 100 100 100 100 97.7 97.7 97.7 36.4 90.9 95.5 18
(88) (88) (88) (88) (88) (88) (88) (88) (88) (88)
2008-2009 92 60 59 55 48 0 20
Ampicillin %
Amoxicillin +
clavulanic acid %
Aztreonam %
Cefepime %
Ceftriaxone %
Cefuroxime %
Cefoperazone %
Cefotaxime %
Ceftazidime %
Imipenem %
Gentamicin %
701
Trends in antimicrobial resistance in Malaysia
Table IV: The Prevalence of Antibiotic-Resistant Staphylococcus aureus in Malaysia
702
Year Type of antibiotics Source*
Penicillin %
Oxacillin %
Ampicillin %
Cefoxitin %
Amikacin %
Gentamicin %
Erythromycin %
Ciprofloxacin %
Co-Trimoxazole %
Clindamycin %
Linezolid %
Vancomycin %
1990-1991 100 92 98 94 0 28
(539) (539) (539) (539) (539)
2002-2007 100 92 98 94 0 29
Systematic / Narrative Review Article
Ampicillin %
Vancomycin %
Teicoplanin %
Gentamicin %
Linezolid %
Tazobactam-
piperacillin %
Erythromycin %
Tetracycline %
Enterococcus faecium
2007-2008 100 100 100 50 0 34
(3) (3) (3) (3) (3)
703
Trends in antimicrobial resistance in Malaysia
14-Trends00102_3-PRIMARY.qxd 9/3/21 4:08 PM Page 704
registered with the Ministry of Health for food and animal ETHICAL APPROVAL
practice, the majority of these antibiotics are not advisable This review article does not contain any studies related to
for veterinary purposes by WHO. It was suggested that the human participants or animals performed by any of the
growth of promoter agents that are not used for human authors.
therapeutic reasons should be used in livestock farming
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