Next Article in Journal
Occurrence and Quantitative Microbial Risk Assessment of Methicillin-Resistant Staphylococcus aureus (MRSA) in a Sub-Catchment of the Yodo River Basin, Japan
Previous Article in Journal
Occurrence and Molecular Characterization of Multidrug-Resistant Vegetable-Borne Listeria monocytogenes Isolates
Previous Article in Special Issue
The Molecular Characterization of Virulence Determinants and Antibiotic Resistance Patterns in Human Bacterial Uropathogens
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Antibiotics
Volume 11
Issue 10
10.3390/antibiotics11101354
antibiotics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Extended Spectrum- and Carbapenemase-Based β-Lactam Resistance in the Arabian Peninsula—A Descriptive Review of Recent Years

by
John Philip Hays
1,
Kazi Sarjana Safain
2,
Mohammed Suliman Almogbel
3,
Ihab Habib
4 and
Mushtaq Ahmad Khan
5,6,*
1
Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Centre (Erasmus MC), Rotterdam 3015 GD, the Netherlands
2
Department of Microbiological Sciences, North Dakota State University, Fargo, ND 58108, USA
3
College of Applied Medical Sciences, University of Hail, Hail 4030, Saudi Arabia
4
Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, United Arab Emirates University, Al Ain P.O. Box 1555, United Arab Emirates
5
Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University (UAEU), Al Ain P.O. Box 15551, United Arab Emirates
6
Zayed Center for Health Sciences, United Arab Emirates University (UAEU), Al Ain P.O. Box 15551, United Arab Emirates
*
Author to whom correspondence should be addressed.
Antibiotics 2022, 11(10), 1354; https://doi.org/10.3390/antibiotics11101354
Submission received: 29 July 2022 / Revised: 29 September 2022 / Accepted: 1 October 2022 / Published: 5 October 2022
(This article belongs to the Special Issue Antibiotic-Resistant Enterobacteriaceae)
Browse Figure
Review Reports Versions Notes

Abstract

:
Antimicrobial resistance (AMR) is a global problem that also includes countries of the Arabian Peninsula. Of particular concern, is the continuing development of extended-spectrum β-lactamases (ESBLs) in the countries of this region. Additionally, antibiotic treatment options for ESBL-producing bacteria are becoming limited, primarily due to the continuing development of carbapenem resistance (CR), carbapenems being frequently used to treat such infections. An overview of recent publications (2018–2021) indicates the presence of ESBL and/or CR in patients and hospitals in most countries of the Arabian Peninsula, although the delay between microbial isolation and publication inevitably makes an accurate analysis of the current situation rather difficult. However, there appears to be greater emphasis on CR (including combined ESBL and CR) in recent publications. Furthermore, although publications from Saudi Arabia are the most prevalent, this may simply reflect the increased interest in ESBL and CR within the country. Enhanced ESBL/CR surveillance is recommended for all countries in the Arabian Peninsula.

1. Introduction

The bacterial extended-spectrum β-lactamase (ESBL) phenotype is mainly associated with members of the Enterobacteriaceae family, which are part of the normal gut microbiota. However, these bacteria may become pathogenic when associated with urinary tract and bloodstream infections [1]. Multiple enzymes and genes may confer the ESBL phenotype [2], thereby making treatment with β-lactam antibiotics, such as third-generation cephalosporins (e.g., cefotaxime, ceftriaxone, ceftazidime) problematic. Of particular concern is the rapid rise in the blaCTX-M-15 enzyme, which was first detected in Escherichia coli isolated from India in 2001 [3] and has rapidly spread worldwide [4,5]. This type of AMR (i.e., CTX-M extended-spectrum β-lactamases) has been shown to have an environmental origin [6].
The consequence of the increasing resistance to cephalosporins has been a worldwide surge in the use of carbapenem antibiotics (originally effective against ESBL-positive bacteria). This phenomenon, in turn, is leading to the global and regional emergence and spread of carbapenem-resistant bacteria (mainly Enterobacteriaceae), potentially representing another formidable threat to public health [7,8,9,10]. Currently, carbapenem antibiotics, such as imipenem, ertapenem, meropenem, and doripenem, have a broad spectrum of activity and are crucial for treating life-threatening nosocomial (hospital-acquired) ESBL and MDR infections. However, the emergence of resistance to carbapenem antibiotics (mainly via the production of carbapenem-cleaving enzymes) is jeopardizing their use globally. The carbapenemase enzymes are categorized into four ‘Ambler’ classes based on their protein sequence similarity or their substrate and inhibitor profiles (Bush–Jacoby–Medeiros classification) [11]. The global spread of both ESBL and CR (sometimes carried in the same bacterial isolate) is a huge challenge to global healthcare systems, including those of countries in the Arabian Peninsula.
Countries in the Arabian Peninsula include Bahrain, Iraq, Jordan, Kuwait, Oman, Qatar, the Kingdom of Saudi Arabia (KSA), the United Arab Emirates (UAE), and Yemen [12]. Among the most common resistance phenotypes that have appeared in this region and globally within the past few decades are the ESBL and CR phenotypes. In this update, the authors highlight the most recent publications available in PubMed (https://pubmed.ncbi.nlm.nih.gov/) relating to ESBL and CR in the Arabian Peninsula between 2018 and 2021.

2. Results

The majority of recent publications in the Arabian Peninsula (from 2018 to 2021) relate to carbapenem-resistant bacteria. This emphasis is most likely due to the recent development of CR in this region. Additionally, Saudi Arabia had the most publications relating to ESBL and CR, which probably reflects differences in the amount of AMR research being performed in countries of the Arabian Peninsula rather than differences in AMR incidence.

2.1. Extended-Spectrum β-Lactamase Infections in the Arabian Peninsula

JORDAN: Between June and October 2016, the analysis of 121 E. coli isolates from urinary tract infections among patients in two tertiary hospitals in Amman, Jordan, found that 62% (75/121) of the isolates were ESBL producers. blaCTX-M-group-1 genes were the most predominant (32/75), followed by combined blaCTX-M-group-1 and blaSHV genes (15/75). Risk factors included previous hospitalization and use of a urinary catheter [13].
IRAQ: In Erbil, Iraqi Kurdistan, 81 P. aeruginosa isolates collected from hospitalized patients between 2012 and 2013 showed the presence of blaVEB (30%), blaprn (17%), and ESBL blaPME (5%) [14]. In 2019, a study performed in the same city using urinary tract infection-associated isolates of E. coli (48 isolates) and K. pneumoniae (20 isolates) from 2016 indicated that the ESBL genes were distributed as follows: 81% blaTEM, 16.2% blaSHV, 32.4% blaCTX-M and 64.7% blaTEM, 35.2% blaSHV, 41.1% blaCTX-M, respectively. The isolates were obtained from patients with thalassemia [15].
QATAR: Perez-Lopez et al. used whole-genome sequencing to determine the molecular characteristics of 254 E. coli and 73 K. pneumoniae isolates from children in Qatar, with the most frequent sequence types being ST131 and ST307, respectively. blaCTX-M-type ESBLs were found in 326 isolates, with the majority consisting of blaCTX-M-15 (87.8%) [16]. The presence of recently described colistin-resistance genes (mcr-9 and mcr-1) has also been reported in ESBL-producing K. oxytoca and E. coli isolates from Qatar [17,18].
SAUDI ARABIA: A retrospective research of 72 (24 E. coli and 48 K. pneumoniae) suspected Neonatal Intensive Care Unit (NICU) outbreaks in Ha’il in 2014 showed that the majority of isolates (61 of E. coli and K. pneumoniae) were ESBL-positive, with high-level resistance to oxyimino-cephalosporins via the simultaneous production of blaCTX-M-15 and blaSHV-12. All K. pneumoniae isolates (42) were ST14, and all E. coli isolates (19) were ST131 [19]. Records from 2016 of a medical complex in Dammam (Eastern region of Saudi Arabia) showed that the ESBL isolates comprised 50% of the 176 E. coli and 42.1% of the 148 K. pneumoniae isolates [20]. Investigation of 211 clinical ESBL-producing E. coli isolates showed that 16 isolates were resistant to >10 antibiotics and the most common sequence type was ST131. The primary ESBL genes found were blaCTX-M and blaTEM [21]. From 2017 to 2018, 351 out of 1151 (30.5%) isolates obtained from clinical specimens at a University Medical college in Taif were found to be ESBL producers. These comprised 62.7% (220/351) E. coli and 23.6% (83/351) K. pneumoniae, with the distribution of the blaCTX-M gene being higher (87%) than that of the blaTEM (74.9%) and blaSHV (29.4%) genes [22]. Sixty-seven of one hundred E. coli urine isolates from a hospital in Riyadh in 2018 had the ESBL phenotype; 31/33 (93.94%) of the isolates were associated with the blaCTX-M gene, and all of them contained at least the blaCTX-M-15 gene [23]. A prospective, cross-sectional study of 311 Gram-negative bacteria (GNB) recovered from various clinical samples from a hospital in the Bisha Province between 2017 and 2018 indicated that 27% of the isolates were ESBL producers, most commonly of E. coli and K. pneumoniae. Interestingly, ESBL-producing GNB were most commonly found in the surgical and ICU departments, and co-production of ESBL and AmpC β-lactamases was found in 11.6% of GNB [24]. Diverse ESBL genes were found in MDR Enterobacteriaceae and Acinetobacter baumannii from clinical samples collected between 2017 and 2018. Seventy-eight out of one hundred seventy-three MDR isolates exhibited ESBL production in the presence of blaTEM (84.7%), blaCTX-M-15 (33.3%), and blaSHV (2.7%), as confirmed by PCR and sequencing [25]. The blaCTX-M Group 1 and blaCTX-M Group 26 genes were recently reported for the first time in 2018–2019 clinical isolates obtained from the Jizan region [26]. The presence of MDR (including ESBL- and carbapenem-resistant) hospital isolates of clonally related K. pneumoniae was reported in 2019 [27]. Alasmary reported that 8.94% (11/123) of uropathogens (mainly E. coli [58.5%] and K. pneumoniae [8.1%]) isolated in 2020 from three government hospitals showed ESBL resistance, stating that patients with UTIs in the Najran region are at a high risk of antibiotic resistance, which may be leading to significant problems in outpatient department treatment outcomes [28].
UAE: Ranjan Dash et al. reported that ESBL-producing E. coli and K. pneumoniae were responsible for 75% of community-acquired UTI in a hospital study between 2014 and 2016. The majority of these 399 ESBL isolates were also resistant to antibiotics (ciprofloxacin, 74% and trimethoprim-sulphamethoxazole, 73%) used to treat community-acquired infections [29]. In the same year, blaCTX-M-28 was reported in a setting where blaCTX-M-15 was predominant [30].
YEMEN: In 2013, 41 ciprofloxacin-resistant E. coli strains were isolated from a variety of clinical specimens, of which 63.4% (26/41) were ESBL producers. blaCTX-M-15 was detected in all the isolates. Additionally, 36.5% (15/41) of these isolates were genotyped as ST131 E. coli strains [31]. A study in two hospitals in Sana’a City, during 2014–2015, indicated that 44/130 ESBL-producing E. coli (33.8%) could be isolated from a range of clinical samples, including urine, wound exudates, sputum samples, blood, peritoneal fluid, vaginal swabs, and cerebrospinal fluid (CSF). These isolates were associated with the elderly, previously hospitalized patients with a hospital stay of more than 22 days, diabetic patients, and patients who had received a third-generation antibiotic therapy [32].
For a brief overview of the text see Table 1.

2.2. Carbapenemase-Based Infections in the Arabian Peninsula

In a study of double-carbapenemase producers in the Arabian Peninsula, it was found that the location of the carbapenemase genes on transposons (Tn2013) and plasmids (IncHI1b, IncFIb/FII, and IncL/M) contributed equally to their emergence [33].
BAHRAIN: Of the 50 P. aeruginosa isolates from three hospitals in Bahrain (year of isolation not reported), 19 were found to carry blaVIM, one blaNDM-1, and one both blaVIM and blaNDM-1 [34]. In another study, 549 of the 631 carbapenem-resistant Enterobacteriaceae (CRE) isolates collected within a 6-year period (2012–2017) were found to be K. pneumoniae, followed by E. coli (50/631). The elderly population and an ICU admission were found to be important risk factors for CRE acquisition. Notably, there was a rapid increase in CRE up to 2015 (45.4 cases per 10,000 patient admissions), followed by a gradual decrease in 2016–2017, which was attributed to the introduction of an ‘intense CRE control program’ involving infection control units and microbiology laboratories [35].
IRAQ: Using a PubMed literature search, Moghnieh et al. found 67 relevant articles from 2015 to 2020 related to AMR trends in Iraq, Jordan, and Lebanon and noted an increased CR in the A. baumannii species in all the three countries. Publications from Iraq and Jordan indicate that Enterobacteriaceae possess high rates of cephalosporin resistance. The most frequently observed resistance mechanisms in Gram-negative bacteria are genetic modifications, which facilitate the increased expression of antibiotic-inactivating enzymes and reduce bacterial cell permeability. Their conclusion was that there was a “concerning rise in AMR,” as well as a need for an improved understanding of the underlying mechanisms [36].
JORDAN: In Amman, 1% of clinical specimens (23/2759 isolates between 2013 and 2014) were found to have CR, including K. pneumoniae, Enterobacter cloacae complex, and E. coli, with the presence of blaNDM-1, blaOXA-48, and blaVIM-4 genes [37]. Subsequently, the analysis of 86 A. baumannii and Acinetobacter species isolates from three major hospitals in 2018 showed that 90.6% of them were carbapenem-resistant, with expression of the blaOXA-51-like (89.5%), blaOXA-23-like (88.3%), and blaNDM-1 (10.4%) genes. The number of extensively drug-resistant (XDR) isolates was reportedly ‘alarming’ [38]. Hayajneh et al. used non-linear time-series methods to inform antibiotic policies to determine a threshold for third-generation cephalosporin and carbapenem use in a 533-bed tertiary teaching hospital in Irbid. Additionally, the use of alcohol-based hand rubs significantly reduced the incidence of carbapenem-resistant A. baumannii (CRAb), according to a retrospective study of ecological data collected between 2014 and 2019 [39]. In the same hospital, another retrospective study conducted between 2014 and 2019 concluded that antibiotic stewardship interventions led to significant reductions in antibiotic use (including third-generation cephalosporin and carbapenems) and had a significant impact on reducing the CRAb levels [40].
KUWAIT: The emergence of blaOXA-181 was found to be of concern in CRE from rectal swabs in two major hospitals between 2017 and 2018. Of the 590 patients examined, 58 were positive for CRE, with 38 colonized by blaOXA-181, 5 by blaOXA-48, and 1 by blaKPC-2 [41]. Asymptomatic intestinal carriage of carbapenem- and multidrug-resistant, ESBL-producing Enterobacteriaceae (mainly associated with E. coli and K. pneumoniae) was found to be relatively common in 405 food handlers (FH) in Kuwait between 2016 and 2018 [42]. Moghnia et al. also compared fecal CRE isolates between FH (n = 681) and patients in intensive care (ICP; n = 95) during the same period. Heterogeneous isolates were detected, with the distribution of E. coli in FH and ICP being 62.4% and 16.8%, respectively; the distribution was 2.6% and 72.6%, respectively, for K. pneumoniae. Thirty-six isolates were CRE (5.3%) in FHs, and 87 (91.6%) in ICPs, with a relatively high incidence of blaKPC in FHs and blaOXA in ICPs [43].
More recently, the presence of β-lactamase genes, reduced bacterial permeability, and overexpression of MDR efflux pumps have been associated with 14 non-carbapenemase-resistant Enterobacterales in the same country [44].
OMAN: Whole-genome sequencing was performed on 35 putative carbapenem-resistant E. coli isolates recovered from patients at multiple centers in 2015. CRE (E. coli and K. pneumoniae) was found to be mediated by the production of blaNDM and blaOXA-48 carbapenemases. Twenty-eight percent of these were blaCTX-M-15 producers [45].
QATAR: Qatar has also recently reported on CRE, focusing on the mcr-1 (colistin resistance) gene in two E. coli isolates carrying blaCTX-M-15 and blaNDM-1, in pediatric ICU patients on routine screening [18,46]. Additionally, Pérez-López et al. investigated 72 carbapenemase-producing Enterobacterales from pediatric fecal specimen (61 children <18 years old) between 2018 and 2020 and found that E. coli (65.3%) and K. pneumoniae (30.6%) were the most common species. Genetic characterization of the 72 isolates indicated the presence of blaNDM-5 (30.8%), blaNDM-1 (19.2%), and blaOXA-181 (19.2%). The authors referred to the apparent sporadic introduction of antibiotic resistance within the healthcare setting in the Arabian Peninsula via asymptomatic carriers, particularly, those who visited or received healthcare in (nearby) countries with endemic antibiotic resistance [47]. In another study, 149 CRE (89 K. pneumoniae and 38 E. coli) isolates were found between 2014 and 2017, and the associated genes included blaNDM-1 (30.2%) and blaOXA-48 (19.5%) [48].
SAUDI ARABIA: Alotaibi reported on CRE during 2010–2018, indicating that 88% of the CRE isolates belonged to K. pneumoniae, and 11% to E. coli species [49]. In another study, K. pneumoniae and Enterobacter cloacae isolates from 2015 were found to contain blaNDM-1 and blaVIM-1, respectively [27]. The carriage of these genes was found to be related to two large plasmids (>60kb), with isolates being MDR. Seventy-one K. pneumoniae isolates from Riyadh between 2011 and 2012 carried either blaOXA-48 (67.6%) or blaNDM-1 (8.5%), with blaCTX-M-15 (66.2%) and blaCTX-M-14 (21%) also being detected. Alsaleh et al. evaluated the appropriateness of carbapenem and piperacillin–tazobactam use in a tertiary-care hospital between 2016 and 2017. Of the 4929 prescriptions, only 2787 (58.6%) were considered to have been appropriately prescribed, with inappropriateness being attributed to too-broad a spectrum of activity (44.6%), antimicrobial use without culture (32.4%), and failure to suitably de-escalate the antimicrobials (19.9%) [50]. FIIK and L/M were the most predominant plasmid replicon types detected (69% and 67%, respectively) [51]. In Southern Saudi Arabia in 2015, a survey of 54 K. pneumoniae isolates with reduced sensitivity to carbapenem antibiotics indicated that the majority of isolates carried blaOXA-48 (81.5%), and 7.4% carried blaNDM-1 (7.4%) [52]. Three years later, a collection of 519 carbapenem-resistant isolates from 13 Ministry of Health tertiary-care hospitals in five different regions of Saudi Arabia indicated that 84.7% (440/519) were CRE, with K. pneumoniae (456/591) being the most prevalent species. blaOXA-48, blaNDM-1, blaOXA-48, and blaNDM-1 were the most prevalent carbapenemase genes detected [53]. A range of CR genes were found in 32 A. baumannii isolates from Taif in 2017, including blaOXA-51, blaIPM, blaNDM, and blaOXA-23 [54]. In addition, in 2017, K. pneumoniae isolates from the western region of Saudi Arabia were found to co-harbor the triple carbapenemase genes blaKPC, blaNDM-1, and blaOXA-48 [55]. In a selection of 200 carbapenem-resistant isolates (K. pneumoniae, E. coli, and P. aeruginosa) between 2014 and 2019, the most prevalent carbapenemase genes were blaOXA-48 (n=83, 41.5%), blaNDM-1 (n=19, 2.5%), and both blaOXA-48 and blaNDM-1 (n=5, 2.5%) [56]. In the Jizan province, 50 third-generation cephalosporin- and carbapenem-resistant isolates were collected between 2018 and 2019; there was a high incidence of blaCTX-M-Group1 cephalosporin resistance [26]. Worryingly, Al-Hamad et al. reported on clinical and environmental isolates from a hospital in the eastern region of Saudi Arabia in 2014, where 74 of the 208 (35.5%) surfaces tested were contaminated with carbapenem-resistant A. baumannii. Furthermore, all clinical and environmental isolates were found to be multidrug- or extremely drug-resistant. The range of carbapenemase genes found included blaOXA-66, blaOXA-69, ISAba1-linked blaOXA-23, ISAba1-linked blaOXA-94, blaGES-1, and blaNDM-1 [57]. High rates of MDR and blaOXA-23 and blaOXA-51 in A. baumannii were reported in isolates collected from 2006 to 2014 [58]. In 2018, the first report of carbapenem-resistant Providencia stuartii was published, although no genetic analysis was performed [59]. A Salmonella enterica serovar Kentucky isolate (first described in poultry) carrying blaOXA-48 was isolated from a Sudanese patient in Riyadh during a visit to Saudi Arabia in 2020 [60]. However, a preliminary search in PubMed indicated no further detection of this blaOXA-48-carrying strain in Saudi Arabia. Unsurprisingly, CR genes (in this case, blaKPC) have been found in a hospital sewage tank and municipal sewage treatment plant [61]. A retrospective, matched case–control study of pediatric patients with CRE infection in Riyadh, between January 2016 and 2017 indicated that recent surgery, antibiotic exposure, and the use of invasive procedures were significant risk factors for CRE colonization and infection [62].
UAE: Analysis of 295 carbapenem-producing Enterobacteriaceae from 2009 to 2014 indicated that 10.2% of them carried IncX3 plasmids, with blaNDM-1, blaNDM-4, blaNDM-5, blaNDM-7, blaOXA-181, or blaKPC-2 genes. The species represented were 13 E. coli, 13 K. pneumoniae, 2 Enterobacter cloacae, 1 Citrobacter freundii, and 1 Morganella morganii [63]. In a comparative study of two detection methods for carbapenem-resistant bacteria, a screening of 1813 rectal swabs from a clinic in Abu Dhabi over a period of 7 months yielded a positivity rate of 3.4%, mostly K. pneumoniae (22/61), with nine of these carrying the blaOXA-48-like and blaNDM-2 genes [64].
YEMEN: Recently, Alsharapy et al. provided the first description of OXA-48-like-producing Enterobacteriaceae and NDM-5-producing E. coli in a hospital in Sana’a. Investigations into 27 isolates having decreased carbapenem-sensitivity (from a range of clinical specimens) showed that the majority of species were K. pneumoniae (18/27) and E. coli (6/27), with blaNDM-1 and blaOXA-48, and carrying the blaOXA-232 and blaOXA-181 genes [65].
Finally, although the situation may have changed in recent years, the majority (95.5%) of 1192 non-repeat CRE isolates from the Arabian Peninsula (as a whole) between 2009 and 2017 were found to be aztreonam–avibactam susceptible, followed by colistin- (79.8%), fosfomycin- (71.8%), and tigecycline- (59.9%) susceptible isolates [66]. In their study on FHs and ICPs, Moghnia et al. recommended that a multinational study be conducted to monitor the spread of AMR genes in the Arabian Peninsula [43]. In addition, the presence of blaNDM-1, blaOXA-48, blaOXA-162, blaOXA-232, blaKPC-2, and blaNDM-1 + blaOXA-48 was observed in 39 carbapenem-resistant K. pneumoniae ST14 strains isolated from 13 hospitals in Bahrain, Saudi Arabia, and the UAE between 2011 and 2016 [67].
For a brief overview of the text see Table 2.

3. Materials and Methods

A PubMed literature search was performed up to 23 December, 2021, using the following search criteria: ("extended spectrum beta lactamase"[Title] OR "extended-spectrum beta lactamase"[Title] OR "extended spectrum beta-lactamase"[Title] OR "extended-spectrum beta-lactamase"[Title] OR "extended spectrum β lactamase"[Title] OR "extended-spectrum β lactamase"[Title] OR "extended spectrum β-lactamase"[Title] OR "extended-spectrum β-lactamase"[Title] OR "ESBL"[Title] OR "ctx-m"[Title] OR "carbapenem"[Title] OR "carbapenemase"[Title]) AND ("Arabian peninsula"[Title] OR "bahrain"[Title] OR "iraq"[Title] OR "jordan"[Title] OR "kuwait"[Title] OR "oman"[Title] OR "qatar"[Title] OR "saudi arabia"[Title] OR "united arab emirates"[Title] OR "uae"[Title] OR "yemen"[Title]) AND ("2018/01/01"[Date - Publication]: "3000"[Date - Publication]). This generated 56 results, including one corrigendum. All publications were included in the current study and some publications (e.g., review articles) described research performed prior to 2018. Only English language articles were included (Figure 1), and where appropriate, risk factors associated with AMR were described. Searches of databases other than PubMed may have yielded different results.

4. Discussion

There is an inevitable lag between the initial isolation of microbial strains and the eventual publication of AMR results. Therefore, most of the studies published in 2018–2021 relate to isolates obtained several years before their publication. This makes an accurate analysis of the current state of affairs regarding the epidemiology of ESBL and CR in the Arabian Peninsula difficult, although this aspect of AMR epidemiological reporting is not restricted to this region of the world. However, recent publications have shown that there is an increasing interest in the epidemiology of CR in this region, most likely due to the increasing number of CR isolations from patients. Further, it is inevitable that the increasing use of carbapenem antibiotics to treat ESBL-related infections will lead to an eventual increase in CR globally, including in the Arabian Peninsula. As such, the steps required to help prevent or slow down the global emergence of CR infections include: i) recognition of the impact of carbapenem prescribing on regional infections and ii) ensuring that appropriate measures are taken towards the responsible prescription of antibiotics. In this respect, the need for a doctor’s prescription, a consultation with infection control teams, an accurate diagnosis of bacterial infections, and antibiotic sensitivity is essential [50]. It is encouraging to note that some of these steps are currently being implemented in the Arabian Peninsula [68,69,70,71].
From this review, it is obvious that most country-specific publications related to ESBL and CR infections were from Saudi Arabia. However, it should be remembered that this does not mean that Saudi Arabia has a larger AMR problem than other countries in the Arabian Peninsula, but suggests that the problem is potentially being more thoroughly investigated in this country [72].
Focusing on publications in PubMed may mean that a few relevant publications could have been omitted from this review. However, we described data obtained from 56 relevant publications, and it is unlikely that the impression obtained by this review would be altered by the addition of any additional publications that may have been missed.

5. Conclusion

Based on the current review, continued and expanded surveillance of ESBL and CR in hospitals and the environment is recommended for all countries in the Arabian Peninsula. Increased funding and the implementation of relevant AMR policies directed at non-specific and specific attributes associated with countries of the Arabian Peninsula, such as migration, religious pilgrimages, and food imports, are particularly recommended.

Author Contributions

K.S.S., M.S.A., I.H. and J.P.H. conceived, read, and approved the manuscript. J.P.H., K.S.S. and M.A.K. contributed to the manuscript writing. M.S.A. and I.H. performed the electronic database search, article screening, data abstraction, and analysis. All authors have read and agreed to the published version of the manuscript

Funding

This work was funded by a grant from the UAE University Start-up Grant Fund (No: G00003463).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable

Conflicts of Interest

The authors declare that they have no competing interests. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

References

  1. Bezabih, Y.M.; Sabiiti, W.; Alamneh, E.; Bezabih, A.; Peterson, G.M.; Bezabhe, W.M.; Roujeinikova, A. The global prevalence and trend of human intestinal carriage of ESBL-producing Escherichia coli in the community. J. Antimicrob. Chemother 2021, 76, 22–29. [Google Scholar] [CrossRef] [PubMed]
  2. Sawa, T.; Kooguchi, K.; Moriyama, K. Molecular diversity of extended-spectrum beta-lactamases and carbapenemases, and antimicrobial resistance. J. Intensive Care 2020, 8, 13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Karim, A.; Poirel, L.; Nagarajan, S.; Nordmann, P. Plasmid-mediated extended-spectrum β-lactamase (CTX-M-3 like) from India and gene association with insertion sequence IS Ecp1. FEMS Microbiol. Lett. 2001, 201, 237–241. [Google Scholar] [PubMed] [Green Version]
  4. Palmeira, J.D.; Cunha, M.V.; Carvalho, J.; Ferreira, H.; Fonseca, C.; Torres, R.T. Emergence and Spread of Cephalosporinases in Wildlife: A Review. Animals 2021, 11, 1765. [Google Scholar] [CrossRef]
  5. Castanheira, M.; Simner, P.J.; Bradford, P.A. Extended-spectrum beta-lactamases: An update on their characteristics, epidemiology and detection. JAC—Antimicrob. Resist. 2021, 3, dlab092. [Google Scholar] [CrossRef]
  6. Poirel, L.; Kämpfer, P.; Nordmann, P. Chromosome-encoded Ambler class A β-lactamase of Kluyvera georgiana, a probable progenitor of a subgroup of CTX-M extended-spectrum β-lactamases. Antimicrob. Agents Chemother. 2002, 46, 4038–4040. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  7. Lynch, J.P.; Clark, N.M.; Zhanel, G.G. Escalating antimicrobial resistance among Enterobacteriaceae: Focus on carbapenemases. Expert Opin. Pharmacother. 2021, 22, 1455–1473. [Google Scholar] [CrossRef]
  8. Safain, K.S.; Bhuyan, G.S.; Hasib, S.H.; Islam, M.S.; Mahmud-Un-Nabi, M.A.; Sultana, R.; Tasnim, S.; Noor, F.A.; Sarker, S.K.; Islam, M.T.; et al. Genotypic and phenotypic profiles of antibiotic-resistant bacteria isolated from hospitalised patients in Bangladesh. Trop. Med. Int. Health 2021, 26, 720–729. [Google Scholar] [CrossRef]
  9. Meletis, G. Carbapenem resistance: Overview of the problem and future perspectives. Ther. Adv. Infect. Dis. 2016, 3, 15–21. [Google Scholar] [CrossRef] [Green Version]
  10. Hawkey, P. Multidrug-resistant Gram-negative bacteria: A product of globalization. J. Hosp. Infect. 2015, 89, 241–247. [Google Scholar] [CrossRef] [PubMed]
  11. Nagshetty, K.; Shilpa, B.M.; Patil, S.A.; Shivannavar, C.T.; Manjula, N.G. An Overview of Extended Spectrum Beta Lactamases and Metallo Beta Lactamases. Adv. Microbiol. 2021, 11, 37–62. [Google Scholar] [CrossRef]
  12. Arabian Peninsula. 2021. Available online: https://en.wikipedia.org/wiki/Arabian_Peninsula (accessed on 29 November 2021).
  13. Al-Jamei, S.A.; Albsoul, A.Y.; Bakri, F.G.; Al-Bakri, A.G. Extended-spectrum β-lactamase producing E. coli in urinary tract infections: A two-center, cross-sectional study of prevalence, genotypes and risk factors in Amman, Jordan. J. Infect. Public Health 2019, 12, 21–25. [Google Scholar] [CrossRef] [PubMed]
  14. Van Burgh, S.; Maghdid, D.M.; Ganjo, A.R.; Mansoor, I.Y.; Kok, D.J.; Fatah, M.H.; Alnakshabandi, A.A.; Asad, D.; Hammerum, A.M.; Ng, K.; et al. PME and Other ESBL-Positive Multiresistant Pseudomonas aeruginosa Isolated from Hospitalized Patients in the Region of Kurdistan, Iraq. Microb. Drug Resist. 2019, 25, 32–38. [Google Scholar] [CrossRef] [PubMed]
  15. Pishtiwan, A.H.; Khadija, K.M. Prevalence of blaTEM, blaSHV, and blaCTX-M Genes among ESBL-Producing Klebsiella pneumoniae and Escherichia coli Isolated from Thalassemia Patients in Erbil, Iraq. Mediterr. J. Hematol. Infect. Dis. 2019, 11, e2019041. [Google Scholar] [PubMed] [Green Version]
  16. Perez-Lopez, A.; Sundararaju, S.; Al-Mana, H.; Tsui, K.M.; Hasan, M.R.; Suleiman, M.; Janahi, M.; al Maslamani, E.; Tang, P. Molecular Characterization of Extended-Spectrum beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Among the Pediatric Population in Qatar. Front. Microbiol. 2020, 11, 581711. [Google Scholar] [CrossRef] [PubMed]
  17. Tsui, C.K.M.; Sundararaju, S.; al Mana, H.; Hasan, M.R.; Tang, P.; Perez-Lopez, A. Draft Genome Sequence of an Extended-Spectrum beta-Lactamase-Producing Klebsiella oxytoca Strain Bearing mcr-9 from Qatar. Microbiol. Resour. Announc 2020, 9, e00429-20. [Google Scholar] [CrossRef]
  18. Tsui, C.K.M.; Sundararaju, S.; Mana, H.A.; Hasan, M.R.; Tang, P.; Perez-Lopez, A. Plasmid-mediated colistin resistance encoded by mcr-1 gene in Escherichia coli co-carrying blaCTX-M-15 and blaNDM-1 genes in pediatric patients in Qatar. J. Glob. Antimicrob. Resist. 2020, 22, 662–663. [Google Scholar] [CrossRef]
  19. Almogbel, M.; Altheban, A.; Alenezi, M.; Al-Motair, K.; Menezes, G.A.; Elabbasy, M.; Hammam, S.; Hays, J.P.; Khan, M.A. CTX-M-15 Positive Escherichia coli and Klebsiella pneumoniae Outbreak in the Neonatal Intensive Care Unit of a Maternity Hospital in Ha’il, Saudi Arabia. Infect. Drug Resist. 2021, 14, 2843–2849. [Google Scholar] [CrossRef]
  20. Aldrazi, F.A.; Rabaan, A.A.; Alsuliman, S.A.; Aldrazi, H.A.; Alabdalslam, M.J.; Alsadiq, S.A.; Alhani, H.M.; Bueid, A.S. ESBL expression and antibiotic resistance patterns in a hospital in Saudi Arabia: Do healthcare staff have the whole picture? J. Infect. Public Health 2020, 13, 759–766. [Google Scholar] [CrossRef]
  21. Yasir, M.; Ajlan, A.M.; Shakil, S.; Jiman-Fatani, A.A.; Almasaudi, S.B.; Farman, M.; Baazeem, Z.M.; Baabdullah, R.; Alawi, M.; Al-Abdullah, N.; et al. Molecular characterization, antimicrobial resistance and clinico-bioinformatics approaches to address the problem of extended-spectrum β-lactamase-producing Escherichia coli in western Saudi Arabia. Sci. Rep. 2018, 8, 14847. [Google Scholar] [CrossRef]
  22. Al-Garni, S.M.; Ghonaim, M.M.; Ahmed, M.M.M.; Al-Ghamdi, A.S.; Ganai, F.A. Risk factors and molecular features of extended-spectrum beta-lactamase producing bacteria at southwest of Saudi Arabia. Saudi Med. J. 2018, 39, 1186–1194. [Google Scholar] [CrossRef] [PubMed]
  23. Alqasim, A.; Jaffal, A.A.; Alyousef, A.A. Prevalence of Multidrug Resistance and Extended-Spectrum beta-Lactamase Carriage of Clinical Uropathogenic Escherichia coli Isolates in Riyadh, Saudi Arabia. Int. J. Microbiol. 2018, 2018, 3026851. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Ibrahim, M.E.; Abbas, M.; Al-Shahrai, A.M.; Elamin, B.K. Phenotypic Characterization and Antibiotic Resistance Patterns of Extended-Spectrum beta-Lactamase- and AmpC beta-Lactamase-Producing Gram-Negative Bacteria in a Referral Hospital, Saudi Arabia. Can. J. Infect. Dis. Med. Microbiol. 2019, 2019, 6054694. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  25. Ibrahim, M.E.; Algak, T.B.; Abbas, M.; Elamin, B.K. Emergence of bla TEM, bla CTX-M, bla SHV and bla OXA genes in multidrug-resistant Enterobacteriaceae and Acinetobacter baumannii in Saudi Arabia. Exp. Ther. Med. 2021, 22, 1450. [Google Scholar] [CrossRef]
  26. Sobia, F.; Qurashi, S.N.; Ghailan, K.Y. Occurrence of bla CTX-MGp1 and bla CTX-MGp26 in third generation cephalosporin-resistant and carbapenem- resistant bacterial isolates from southwest region of Saudi Arabia-a preliminary study. Saudi J. Biol. Sci. 2021, 28, 5408–5413. [Google Scholar] [CrossRef]
  27. Al-Agamy, M.H.; El-Mahdy, T.S.; Radwan, H.H.; Poirel, L. Cooccurrence of NDM-1, ESBL, RmtC, AAC(6’)-Ib, and QnrB in Clonally Related Klebsiella pneumoniae Isolates Together with Coexistence of CMY-4 and AAC(6’)-Ib in Enterobacter cloacae Isolates from Saudi Arabia. Biomed. Res. Int. 2019, 2019, 6736897. [Google Scholar] [CrossRef] [Green Version]
  28. Alasmary, M.Y. Antimicrobial Resistance Patterns and ESBL of Uropathogens Isolated from Adult Females in Najran Region of Saudi Arabia. Clin. Pract. 2021, 11, 650–658. [Google Scholar] [CrossRef]
  29. Dash, N.R.; Albataineh, M.T.; Alhourani, N.; Khoudeir, A.M.; Ghanim, M.; Wasim, M.; Mahmoud, I. Community-acquired urinary tract infections due to extended-spectrum beta-lactamase-producing organisms in United Arab Emirates. Travel Med. Infect. Dis. 2018, 22, 46–50. [Google Scholar] [CrossRef]
  30. Alfaresi, M.; Sing, G.K.; Senok, A. First Report of blaCTX-M-28 in Enterobacteriaceae Isolates in the United Arab Emirates. J. Pathog. 2018, 2018, 1304793. [Google Scholar] [CrossRef] [Green Version]
  31. Alsharapy, S.A.; Yanat, B.; Lopez-Cerero, L.; Nasher, S.S.; Diaz-De-Alba, P.; Pascual, A.; Rodriguez-Martinez, J.-M.; Touati, A. Prevalence of ST131 Clone Producing Both ESBL CTX-M-15 and AAC (6′) Ib-cr Among Ciprofloxacin-Resistant Escherichia coli Isolates from Yemen. Microb. Drug Resist. 2018, 24, 1537–1542. [Google Scholar] [CrossRef]
  32. Nasher, S.; Alsharapy, S.; Al-Madhagi, A.; Zakham, F. Epidemiology of extended-spectrum beta-lactamase producing Escherichia coli from hospital settings in Yemen. J. Infect. Dev. Ctries. 2018, 12, 953–959. [Google Scholar] [CrossRef] [PubMed]
  33. Al-Baloushi, A.E.; Pal, T.; Ghazawi, A.; Sonnevend, A. Genetic support of carbapenemases in double carbapenemase producer Klebsiella pneumoniae isolated in the Arabian Peninsula. Acta Microbiol. Et Immunol. Hung. 2018, 65, 135–150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Joji, R.M.; Al-Rashed, N.; Saeed, N.K.; Bindayna, K.M. Detection of VIM and NDM-1 metallo-beta-lactamase genes in carbapenem-resistant Pseudomonas aeruginosa clinical strains in Bahrain. J. Lab. Physicians 2019, 11, 138–143. [Google Scholar] [CrossRef] [PubMed]
  35. Saeed, N.K.; Alkhawaja, S.; Azam, N.F.A.E.M.; Alaradi, K.; Al-Biltagi, M. Epidemiology of carbapenem-resistant Enterobacteriaceae in a Tertiary Care Center in the Kingdom of Bahrain. J. Lab. Physicians 2019, 11, 111–117. [Google Scholar] [CrossRef] [PubMed]
  36. Moghnieh, R.A.; Moussa, J.A.; Aziz, M.A.; Matar, G.M. Phenotypic and genotypic characterisation of cephalosporin-, carbapenem- and colistin-resistant Gram-negative bacterial pathogens in Lebanon, Jordan and Iraq. J. Glob. Antimicrob. Resist. 2021, 27, 175–199. [Google Scholar] [CrossRef] [PubMed]
  37. Aqel, A.A.; Findlay, J.; Al-Maayteh, M.; Al-Kaabneh, A.; Hopkins, K.L.; Alzoubi, H.; Masalha, I.; Turton, J.; Woodford, N.; Ellington, M.J. Characterization of Carbapenemase-Producing Enterobacteriaceae from Patients in Amman, Jordan. Microb. Drug Resist. 2018, 24, 1121–1127. [Google Scholar] [CrossRef]
  38. Ababneh, Q.; Aldaken, N.; Jaradat, Z.; al Sbei, S.; Alawneh, D.; Al-Zoubi, E.; Alhomsi, T.; Saadoun, I. Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii isolated from three major hospitals in Jordan. Int. J. Clin. Pract 2021, 75, e14998. [Google Scholar] [CrossRef]
  39. Hayajneh, W.A.; Al-Azzam, S.; Yusef, D.; Lattyak, W.J.; Lattyak, E.A.; Gould, I.; Lopez-Lozano, J.M.; Conway, B.R.; Conlon-Bingham, G.; Aldeyab, M.A. Identification of thresholds in relationships between specific antibiotic use and carbapenem-resistant Acinetobacter baumannii (CRAb) incidence rates in hospitalized patients in Jordan. J. Antimicrob. Chemother 2021, 76, 524–530. [Google Scholar] [CrossRef]
  40. Yusef, D.; Hayajneh, W.A.; Issa, A.B.; Haddad, R.; Al-Azzam, S.; Lattyak, E.A.; Lattyak, W.J.; Gould, I.; Conway, B.R.; Bond, S.; et al. Impact of an antimicrobial stewardship programme on reducing broad-spectrum antibiotic use and its effect on carbapenem-resistant Acinetobacter baumannii (CRAb) in hospitals in Jordan. J. Antimicrob. Chemother. 2021, 76, 516–523. [Google Scholar] [CrossRef]
  41. Al Fadhli, A.H.; Jamal, W.Y.; Rotimi, V.O. Prevalence of carbapenem-resistant Enterobacteriaceae and emergence of high rectal colonization rates of blaOXA-181-positive isolates in patients admitted to two major hospital intensive care units in Kuwait. PLoS ONE 2020, 15, e0241971. [Google Scholar] [CrossRef]
  42. Moghnia, O.H.; Rotimi, V.O.; Al-Sweih, N.A. Monitoring antibiotic resistance profiles of faecal isolates of Enterobacteriaceae and the prevalence of carbapenem-resistant isolates among food handlers in Kuwait. J. Glob. Antimicrob. Resist. 2021, 25, 370–376. [Google Scholar] [CrossRef] [PubMed]
  43. Moghnia, O.H.; Rotimi, V.O.; Al-Sweih, N.A. Preponderance of bla KPC-Carrying Carbapenem-Resistant Enterobacterales Among Fecal Isolates from Community Food Handlers in Kuwait. Front. Microbiol. 2021, 12, 737828. [Google Scholar] [CrossRef] [PubMed]
  44. Al Fadhli, A.; Jamal, W.; Rotimi, V.O. Molecular characterization of rectal isolates of carbapenemase-negative carbapenem-resistant enterobacterales obtained from ICU patients in Kuwait by whole-genome sequencing. J. Med. Microbiol. 2021, 70, 001409. [Google Scholar] [CrossRef]
  45. Al-Farsi, H.M.; Camporeale, A.; Ininbergs, K.; Al-Azri, S.; Al-Muharrmi, Z.; Al-Jardani, A.; Giske, C.G. Clinical and molecular characteristics of carbapenem non-susceptible Escherichia coli: A nationwide survey from Oman. PLoS ONE 2020, 15, e0239924. [Google Scholar] [CrossRef] [PubMed]
  46. Tsui, C.K.M.; Sundararaju, S.; Mana, H.A.; Hasan, M.R.; Tang, P.; Perez-Lopez, A. Corrigendum to “Plasmid-mediated colistin resistance encoded by mcr-1 gene in Escherichia coli co-carrying blaCTX-M-15 and blaNDM-1 genes in pediatric patients in Qatar”. J. Glob. Antimicrob. Resist. 2020, 23, 472. [Google Scholar] [CrossRef]
  47. Perez-Lopez, A.; Sundararaju, S.; Tsui, K.M.; Al-Mana, H.; Hasan, M.R.; Suleiman, M.; al Maslamani, E.; Imam, O.; Roscoe, D.; Tang, P. Fecal Carriage and Molecular Characterization of Carbapenemase-Producing Enterobacterales in the Pediatric Population in Qatar. Microbiol. Spectr. 2021, 9, e0112221. [Google Scholar] [CrossRef] [PubMed]
  48. Abid, F.B.; Tsui, C.K.M.; Doi, Y.; Deshmukh, A.; McElheny, C.L.; Bachman, W.C.; Fowler, E.L.; Albishawi, A.; Mushtaq, K.; Ibrahim, E.B.; et al. Molecular characterization of clinical carbapenem-resistant Enterobacterales from Qatar. Eur. J. Clin. Microbiol. Infect. Dis. 2021, 40, 1779–1785. [Google Scholar] [CrossRef]
  49. Alotaibi, F. Carbapenem-Resistant Enterobacteriaceae: An update narrative review from Saudi Arabia. J. Infect. Public Health 2019, 12, 465–471. [Google Scholar] [CrossRef]
  50. Alsaleh, N.A.; Al-Omar, H.A.; Mayet, A.Y.; Mullen, A.B. Evaluating the appropriateness of carbapenem and piperacillin-tazobactam prescribing in a tertiary care hospital in Saudi Arabia. Saudi Pharm. J. 2020, 28, 1492–1498. [Google Scholar] [CrossRef]
  51. Zaman, T.U.; Alrodayyan, M.; Albladi, M.; Aldrees, M.; Siddique, M.I.; Aljohani, S.; Balkhy, H.H. Clonal diversity and genetic profiling of antibiotic resistance among multidrug/carbapenem-resistant Klebsiella pneumoniae isolates from a tertiary care hospital in Saudi Arabia. BMC Infect. Dis. 2018, 18, 205. [Google Scholar] [CrossRef]
  52. Al-Zahrani, I.A.; Alsiri, B.A. The emergence of carbapenem-resistant Klebsiella pneumoniae isolates producing OXA-48 and NDM in the Southern (Asir) province, Saudi Arabia. Saudi Med. J. 2018, 39, 23–30. [Google Scholar] [CrossRef] [PubMed]
  53. Al-Abdely, H.; AlHababi, R.; Dada, H.M.; Roushdy, H.; Alanazi, M.M.; Alessa, A.A.; Gad, N.M.; Alasmari, A.M.; Radwan, E.E.; Al-Dughmani, H.; et al. Molecular characterization of carbapenem-resistant Enterobacterales in thirteen tertiary care hospitals in Saudi Arabia. Ann. Saudi Med. 2021, 41, 63–70. [Google Scholar] [CrossRef] [PubMed]
  54. El-Badawy, M.F.; Abdelwahab, S.F.; Alghamdi, S.A.; Shohayeb, M.M. Characterization of phenotypic and genotypic traits of carbapenem-resistant Acinetobacter baumannii clinical isolates recovered from a tertiary care hospital in Taif, Saudi Arabia. Infect. Drug Resist. 2019, 12, 3113–3124. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  55. Khan, M.A.; Mohamed, A.M.; Faiz, A.; Ahmad, J. Enterobacterial infection in Saudi Arabia: First record of Klebsiella pneumoniae with triple carbapenemase genes resistance. J. Infect. Dev. Ctries. 2019, 13, 334–341. [Google Scholar] [CrossRef] [Green Version]
  56. Al-Tawfiq, J.A.; Rabaan, A.A.; Saunar, J.V.; Bazzi, A.M. Genotypes and prevalence of carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa in a hospital in Saudi Arabia. Trans. R. Soc. Trop. Med. Hyg. 2022, 116, 50–53. [Google Scholar] [CrossRef]
  57. Al-Hamad, A.; Pal, T.; Leskafi, H.; Abbas, H.; Hejles, H.; Alsubikhy, F.; Darwish, D.; Ghazawi, A.; Sonnevend, A. Molecular characterization of clinical and environmental carbapenem resistant Acinetobacter baumannii isolates in a hospital of the Eastern Region of Saudi Arabia. J. Infect. Public Health 2020, 13, 632–636. [Google Scholar] [CrossRef]
  58. Ibrahim, M.E. Prevalence of Acinetobacter baumannii in Saudi Arabia: Risk factors, antimicrobial resistance patterns and mechanisms of carbapenem resistance. Ann. Clin. Microbiol. Antimicrob. 2019, 18, 1. [Google Scholar] [CrossRef]
  59. Abdallah, M.; Alhababi, R.; Alqudah, N.; Aldyyat, B.; Alharthy, A. First report of carbapenem-resistant Providencia stuartii in Saudi Arabia. N. Microbes. N. Infect. 2018, 26, 107–109. [Google Scholar] [CrossRef]
  60. Alghoribi, M.F.; Desin, T.S.; Alswaji, A.A.; al Alwan, B.H.; Alzayer, M.; Okdah, L.; al Johani, S.; Balkhy, H.H.; Doumith, M. OXA-48 carbapenemase-producing Salmonella enterica serovar Kentucky ST198 isolated from Saudi Arabia. J. Antimicrob. Chemother. 2020, 75, 2006–2008. [Google Scholar] [CrossRef]
  61. Basode, V.K.; Abdulhaq, A.; Alamoudi, M.U.A.; Tohari, H.M.; Quhal, W.A.; Madkhali, A.M.; Hobani, Y.H.; Hershan, A.A. Prevalence of a carbapenem-resistance gene (KPC), vancomycin-resistance genes (van A/B) and a methicillin-resistance gene (mecA) in hospital and municipal sewage in a southwestern province of Saudi Arabia. BMC Res. Notes 2018, 11, 30. [Google Scholar] [CrossRef]
  62. Alzomor, O.A.; Alfawaz, T.S.; Abu-Shaheen, A.; Alshehri, M.A.; al Shahrani, D. A matched case-control study to assess the carbapenem-resistant Enterobacteriaceae infections among hospitalized children at King Fahad Medical City, Riyadh, Saudi Arabia. Saudi Med. J. 2019, 40, 1105–1110. [Google Scholar] [CrossRef] [PubMed]
  63. Mouftah, S.F.; Pal, T.; Darwish, D.; Ghazawi, A.; Villa, L.; Carattoli, A.; Sonnevend, A. Epidemic IncX3 plasmids spreading carbapenemase genes in the United Arab Emirates and worldwide. Infect. Drug Resist. 2019, 12, 1729–1742. [Google Scholar] [CrossRef] [Green Version]
  64. Moubareck, C.A.; Halat, D.H.; Sartawi, M.; Lawlor, K.; Sarkis, D.K.; Alatoom, A. Assessment of the performance of CHROMagar KPC and Xpert Carba-R assay for the detection of carbapenem-resistant bacteria in rectal swabs: First comparative study from Abu Dhabi, United Arab Emirates. J. Glob. Antimicrob. Resist. 2020, 20, 147–152. [Google Scholar] [CrossRef] [PubMed]
  65. Alsharapy, S.A.; Gharout-Sait, A.; Muggeo, A.; Guillard, T.; Cholley, P.; Brasme, L.; Bertrand, X.; Moghram, G.S.; Touati, A.; de Champs, C. Characterization of Carbapenem-Resistant Enterobacteriaceae Clinical Isolates in Al Thawra University Hospital, Sana’a, Yemen. Microb. Drug. Resist. 2020, 26, 211–217. [Google Scholar] [CrossRef]
  66. Sonnevend, A.; Ghazawi, A.; Darwish, D.; Barathan, G.; Hashmey, R.; Ashraf, T.; Rizvi, T.A.; Pál, T. In vitro efficacy of ceftazidime-avibactam, aztreonam-avibactam and other rescue antibiotics against carbapenem-resistant Enterobacterales from the Arabian Peninsula. Int. J. Infect. Dis. 2020, 99, 253–259. [Google Scholar] [CrossRef]
  67. Mouftah, S.F.; Pal, T.; Higgins, P.G.; Ghazawi, A.; Idaghdour, Y.; Alqahtani, M.; Omrani, A.S.; Rizvi, T.A.; Sonnevend, A. Diversity of carbapenem-resistant Klebsiella pneumoniae ST14 and emergence of a subgroup with KL64 capsular locus in the Arabian Peninsula. Eur. J. Clin. Microbiol. Infect. Dis. 2021. [Google Scholar] [CrossRef] [PubMed]
  68. Hashad, N.; Perumal, D.; Stewart, D.; Tonna, A.P. Mapping hospital antimicrobial stewardship programmes in the Gulf Cooperation Council states against international standards: A systematic review. J. Hosp. Infect. 2020, 106, 404–418. [Google Scholar] [CrossRef]
  69. Nassar, H.; Abu-Farha, R.; Barakat, M.; Alefishat, E. Antimicrobial Stewardship from Health Professionals’ Perspective: Awareness, Barriers, and Level of Implementation of the Program. Antibiotics 2022, 11, 99. [Google Scholar] [CrossRef]
  70. Baraka, M.A.; Alsultan, H.; Alsalman, T.; Alaithan, H.; Islam, M.A.; Alasseri, A.A. Health care providers’ perceptions regarding antimicrobial stewardship programs (AMS) implementation-facilitators and challenges: A cross-sectional study in the Eastern province of Saudi Arabia. Ann. Clin. Microbiol. Antimicrob. 2019, 18, 26. [Google Scholar] [CrossRef] [Green Version]
  71. Alghoribi, M.F.; Balkhy, H.H.; Woodford, N.; Ellington, M.J. The role of whole genome sequencing in monitoring antimicrobial resistance: A biosafety and public health priority in the Arabian Peninsula. J. Infect. Public Health 2018, 11, 784–787. [Google Scholar] [CrossRef]
  72. Benmerzouga, I.; Al-Zammay, S.A.; Al-Shammari, M.M.; Alsaif, S.A.; Alhaidan, T.M.; Aljofan, M. Practices of patients consuming antibiotics and knowledge about antibiotic resistance in Hail region—Saudi Arabia. Future Sci. 2019, 5, FSO420. [Google Scholar] [CrossRef] [PubMed]
Antibiotics 11 01354 g001 550
Figure 1. Flow chart summarizing study selection method.
Figure 1. Flow chart summarizing study selection method.
Antibiotics 11 01354 g001
Table
Table 1. Investigations of Extended Spectrum β-Lactamase infections in the Arabian Peninsula.
Table 1. Investigations of Extended Spectrum β-Lactamase infections in the Arabian Peninsula.
CountrySampleOrganismsResistance PatternResistance GenesReference
JordanPatients with UTI in two tertiary hospitalsE. coli62% (75/121) were ESBL producersPredominance of blaCTX-M-group-1 gene (42.7%), followed by combined blaCTX-M-group-1 and blaSHV genes.[13]
IraqHospitalized patientsP. aeruginosa-blaVEB (30%), blaprn (17%), blaPME (5%)[14]
Patients with UTIE. coli and K. pneumoniae-81% blaTEM, 16.2% blaSHV, and 32.4% blaCTX-M in E. coli. 64.7% blaTEM, 35.2% blaSHV, 41.1 % blaCTX-M in K. pneumoniae[15]
QatarChildrenE. coli and K. pneumoniae 87.8% blaCTX-M-15[16]
Saudi ArabiaNeonates in a suspected NICU outbreakE. coli and K. pneumoniae85% ESBL producers100% E. coli harbored the CTX-M-15 gene. Among the K. pneumoniae isolates, 87.5% were ESBL positive with 92.85% contained the CTX-M-15 gene. [19]
Blood samplesE. coli51.6% has ESBL phenotypePredominance of blaCTX-M-15 [21]
Clinical specimensE. coli and K. pneumoniae30.6% were ESBL producersblaCTX-M (87%), blaTEM (74.9%) and blaSHV (29.4%)[22]
Urine isolatesE. coli67% had ESBL phenotype93.94% associated with the blaCTX-M gene[23]
Clinical specimensE. coli and K. pneumoniae27% were ESBL producersPredominance of ESBL [24]
Clinical specimensMDR Enterobacteriaceae and Acinetobacter baumannii-blaTEM (84.7%), blaCTX-M-15 (33.3%) and blaSHV (2.7%) [25]
Hospital isolatesK. pneumoniaemultidrug resistant (including ESBL and carbapenem resistance)-[27]
Female patients with UTI E. coli (58.5%) was the most commonly isolated organism, followed by K. pneumoniae(8.1%)8.94% showed ESBL producers8.94% showed ESBL resistance[28]
United Arab EmiratesCommunity-acquired UTIE. coli and K. pneumoniae75% ESBL producers with resistance to ciprofloxacin (74%) and trimethoprim-sulphamethoxazole (73%)-[29]
YemenClinical specimensE. coli63.4% (26/41) were ESBL producersCTX-M-15 was present in 63.4% samples and qnrS in 12.2% samples.[31]
Elderly, previously hospitalized patientsE. coli34% were ESBL producers [32]
Table
Table 2. Investigations of Carbapenemase-based infections in the Arabian Peninsula.
Table 2. Investigations of Carbapenemase-based infections in the Arabian Peninsula.
CountrySampleOrganismsResistance PatternResistance GenesReference
BahrainHospitalized patientsP. aeruginosa-38% blaVIM, 2% blaNDM-1, 2% blaVIM, 2% blaNDM-1 [34]
-E. coli and K. pneumoniae87% were carbapenem-resistant Enterobacteriaceae-[35]
JordanClinical specimensK. pneumoniae, Enterobacter cloacae complex and E. coli1% were carbapenem-resistantblaNDM-1, blaOXA-48, and blaVIM-4[37]
Hospitalized patientsA. baumannii and Acinetobacter spp. 90.6% were carbapenem-resistantblaOXA-51, (89.5%), blaOXA-23 (88.3%) and blaNDM-1 (10.4%)[38]
KuwaitRectal swab samples-10% were carbapenem-resistant EnterobacteriaceaeblaOXA-181 and blaOXA-48[41]
FH and ICPE. coli and K. pneumoniaeCRE- 5.3% FH isolates and 91.6% in ICP isolateswith a relatively high number of blaKPC in FH isolates and blaOXA in ICP isolates[43]
Oman Patient samplesCarbapenem-resistant E. coli isolates-59% carbapenemase-producing isolates were NDM and 23% were OXA-48[45]
QatarPediatric fecal carriersCarbapenemase-producing Enterobacterales-blaNDM-5 (30.8%), blaNDM-1 (19.2%), and blaOXA-181 (19.2%)[47]
-Carbapenem-resistant E. coli and K. pneumoniae isolates-blaNDM-1 (30.2%) and blaOXA-48 (19.5%) [48]
Saudi Arabia-E. coli and K. pneumoniae88% CRE-[49]
-K. pneumoniae and Enterobacter cloacae-blaNDM-1 and blaVIM-1[27]
-K. pneumoniaeCarbapenem-resistantblaOXA-48 (81.5%) and 7.4% carried blaNDM-1 (7.4%)[52]
-Predominantly K. pneumoniae84.7% were CREblaOXA-48, blaNDM-1, and combined blaOXA-48 and blaNDM-1[53]
Patient samplesA. baumannii-blaOXA-51, blaIPM, blaNDM and blaOXA-23[54]
-K. pneumoniae-blaKPC, blaNDM-1 and blaOXA-48[55]
-K. pneumoniae, E. coli and P. aeruginosaCarbapenem-resistantblaOXA-48 (41.5%), blaNDM-1 (2.5%) and both blaOXA-48 + blaNDM-1 (2.5%)[56]
Clinical and environmental isolates-35.5% were carbapenem-resistant-[57]
A. baumannii-blaOXA-23 and blaOXA-51[58]
Sudanese patient during a visitSalmonella enterica serovar-blaOXA-48[60]
Sample from a hospital sewage tank--blaKPC[61]
United Arab Emirates-E. coli, K. pneumoniae, Enterobacter cloacae, Citrobacter freundii and Morganella morganii Carbapenem-resistantblaNDM-1, blaNDM-4, blaNDM-5, blaNDM-7, blaOXA-181 or blaKPC-2 genes[63]
Rectal swabsPredominantly K. pneumoniae 3.4% were carbapenem-resistant40.9% carried blaOXA-48 and blaNDM[64]
Yemen-Majority were E. coli and K. pneumoniaeCarbapenem-resistantNDM-1, OXA-48, OXA-232 and OXA-181[65]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Hays, J.P.; Safain, K.S.; Almogbel, M.S.; Habib, I.; Khan, M.A. Extended Spectrum- and Carbapenemase-Based β-Lactam Resistance in the Arabian Peninsula—A Descriptive Review of Recent Years. Antibiotics 2022, 11, 1354. https://doi.org/10.3390/antibiotics11101354

AMA Style

Hays JP, Safain KS, Almogbel MS, Habib I, Khan MA. Extended Spectrum- and Carbapenemase-Based β-Lactam Resistance in the Arabian Peninsula—A Descriptive Review of Recent Years. Antibiotics. 2022; 11(10):1354. https://doi.org/10.3390/antibiotics11101354

Chicago/Turabian Style

Hays, John Philip, Kazi Sarjana Safain, Mohammed Suliman Almogbel, Ihab Habib, and Mushtaq Ahmad Khan. 2022. "Extended Spectrum- and Carbapenemase-Based β-Lactam Resistance in the Arabian Peninsula—A Descriptive Review of Recent Years" Antibiotics 11, no. 10: 1354. https://doi.org/10.3390/antibiotics11101354

APA Style

Hays, J. P., Safain, K. S., Almogbel, M. S., Habib, I., & Khan, M. A. (2022). Extended Spectrum- and Carbapenemase-Based β-Lactam Resistance in the Arabian Peninsula—A Descriptive Review of Recent Years. Antibiotics, 11(10), 1354. https://doi.org/10.3390/antibiotics11101354

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop