Antibacterial Resistance Patterns Among Common Infections in a Tertiary Care Hospital in Saudi Arabia - Cureus

Background

The rapid emergence of antibiotic-resistant bacteria threatens the control of infectious diseases by reducing treatment effectiveness, prolonging illness duration, and increasing healthcare costs. This study aimed to identify the common rate of bacterial resistance against antibacterial agents in tertiary healthcare providers in Saudi Arabia.

Methodology

This retrospective cross-sectional observational study was conducted from May 2016 to December 2019 on 1,151 urinary tract infection (UTI) and respiratory tract infection (RTI) positive cultures collected from participants aged 15 years or older who received antibiotic treatment. The obtained variables included age, gender, diagnosis, antibiotic type, specimen source, culture results, and sensitivity test results.

Results

The most common bacteria in UTI were Escherichia coli (46.7%), followed by Klebsiella pneumoniae (30.5%). Moreover, E. coli was most resistant to ampicillin (56.4%), followed by ceftriaxone (33.8%). Among the respiratory cultures, the most frequently isolated pathogen was Pseudomonas aeruginosa (28.5%), followed by K. pneumoniae (17.6%). The 162 respiratory P. aeruginosa isolates were most resistant to piperacillin/tazobactam (51.9%), followed by ciprofloxacin (25%) and ampicillin (10.6%).

Conclusion

High levels of antibiotic resistance were observed in both Gram-negative and Gram-positive bacteria. This indicates a need for better implementation of antibacterial stewardship and increased awareness of appropriate antibiotic use to limit the rapid spread of antibacterial resistance.

Introduction

The introduction of antibiotics to the medical field was one of the greatest discoveries in the history of medicine. When penicillin was introduced in the 1940s by Alexander Fleming, a new era of therapeutic medicine was established [1]. The outcomes of bacterial infections saw a great turnaround as fatal and severe infections became easily treatable. However, the efficiency of antibiotics has decreased as many available antibiotics are no longer effective along with the emergence of antibiotic-resistant (ABR) strains. Importantly, antibiotic resistance discovery is related to resistance detection in clinical samples; however, the resistance might be discovered earlier according to the observation from laboratory samples.

Globally, it is estimated that ABR infections are responsible for approximately 700,000 deaths per year [2,3]. If no preventative actions are taken, it is predicted that infections caused by ABR bacteria will have a mortality rate exceeding that of cancer and become the most common cause of death by the end of 2050 [2,3]. According to the Centers for Disease Control and Prevention (CDC), approximately 35,900 deaths out of 2,868,700 ABR cases are expected to be reported annually in the United States [2]. In 2012, Aly et al. investigated antimicrobial resistance in 37,295 bacterial isolates collected from different hospitals in the Gulf region. Within this sample, the most prevalent microorganism was Escherichia coli, followed by Klebsiella pneumoniae, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter, Clostridium difficile, and Enterococcus [4]. In addition, a study conducted by the Saudi national surveillance on Gram-positive cocci revealed that 32% of S. aureus belonged to MRSA, 33% of S. pneumoniae were resistant to penicillin G, and 26% of S. pneumoniae were resistant to erythromycin [3]. In the western region of Saudi Arabia, Alam et al. reported bacterial resistance to trimethoprim/sulfamethoxazole (48.6%), ampicillin (49.3%), piperacillin (59.3%), and methicillin (50.3%) [5].

Bacteria have the unique ability to lower or eliminate the antimicrobial efficacy of drugs and chemical agents [6]. This may occur through natural resistance (e.g., β-lactamase production) or acquired resistance [7,8]. Acquired bacterial resistance may occur through four mechanisms. One of these mechanisms is the production of enzymes that modify or inhibit antibiotic action [7-9]. Another mechanism is through changes in the permeability of bacterial cell walls [7]. Bacteria can also acquire resistance through disruptions in protein synthesis [7], alterations in metabolic pathways, or genetic mutations [8]. Finally, bacteria can acquire resistance from the transferred copy of the plasmid (R-plasmid genes) of a previously resistant bacteria [7-9].

The development of antibiotic resistance appears to be inevitable [10]. However, the overuse and misuse of antibiotics are accelerating this process [11]. The misuse of antibiotics is a complex problem driven by several factors related to patients, healthcare providers, and institutional healthcare regulations [12]. Public knowledge, awareness, and attitudes regarding antibiotic use are strong determinants of antibiotic misuse [13]. In a systematic review conducted by Alhomoud et al. in 2017 and demonstrated the use of antibiotics in the Middle East, the overall prevalence of participants who used antibiotics as self-prescription ranged from 19% to 82% [14]. The highest prevalence of self-prescription antibiotics was reported in Yemen and Oman followed by Saudi Arabia [14]. Access to antibiotics without a prescription and gaps in knowledge and safe practices regarding antibiotics' use (e.g., keeping leftover antibiotics from an uncompleted course for future use and sharing antibiotics with others) were among the reported reasons for self-medication with antibiotics [14]. Furthermore, prescribers' knowledge and attitudes regarding antibiotic use and resistance have been reported to determine the quality of antibiotic prescriptions [15]. One core problem underlying improper antibiotic prescription is the lack of sufficient diagnostic tests to rapidly identify pathogens and their antibiotic susceptibility profiles [16]. Another proven risk factor for antibiotic resistance is travel, specifically during the Hajj season, when the acquisition and transmission of infectious diseases (including those caused by ABR bacteria) are common occurrences [17].

The topic of antibiotic resistance has been approached from many perspectives for a wide variety of clinical and social practices and implications. However, the present research specifically aimed to assess the prevalence of ABR infections in Ministry of National Guard-Health Affairs (MNGHA), Jeddah, Saudi Arabia. In a study conducted in the western region of Saudi Arabia, pneumonia was the most prevalent infectious disease reported in patients aged 26-45 years [18]. Additionally, pneumonia and urinary tract infections (UTIs) were the most prevalent forms of infectious diseases among female patients [18]. In the central region of Saudi Arabia, respiratory tract infections (RTIs) and UTIs have been found to be the most frequent complaints encountered in emergency departments [19]. The availability of updated epidemiological data from a given region or community is important not only for the optimization of empirical therapies but also for the implementation of an effective antimicrobial stewardship program in hospitals [20].

Materials & Methods

Selection criteria

An observational cross-sectional quantitative study (with non-probability convenience sampling) was conducted in the MNGHA, Jeddah, Saudi Arabia. For this study, patients were selected according to the following criteria: male and female Saudi inpatients and outpatients aged 15 years or older who had received antibiotic treatments prior to the initiation of the study for UTIs and/or RTIs. This sample excluded the oncology department, patients infected with tuberculosis (TB), and patients infected with human immunodeficiency virus (HIV).

Sample size calculation

The sample size was calculated using Raosoft® software (Raosoft Inc., Seattle, United States). Approximately 231,000 patients received antibiotic treatments in MNGHA, Jeddah, between May 2016 and December 2019. At a 95% confidence level, an estimated 59.1% prevalence of ABR patients, and a 5% margin of error, the required minimum sample size was estimated at 371 samples. All patients who met the sample criteria from May 2016 to December 2019 were included in the study.

Data were obtained from the BESTCare system (ezCaretech, Torrance, California, United States) using a data collection sheet. The collected numerical variables included age and date of diagnosis, and the collected categorical/nominal variables included gender, hospital setting, diagnosis, antibiotic type, specimen source, culture results, and sensitivity test results.

Data analysis

Parametric and non-parametric approaches were used to describe the numerical data (age and date of diagnosis). Percentages were used to describe the categorical variables (gender, hospital setting, diagnosis, antibiotic type, specimen source, type of organism, and sensitivity test results). Chi-square or Fisher exact test was used to compare categorical data, while t-test and ANOVA were used to make comparisons between categorical and numerical variables. A p-value of less than 0.05 was statistically significant. All data were analyzed using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, New York, United States).

Ethical approval

The study was carried out in line with the Helsinki protocol and ethical approval from the Institutional Review Board of King Abdullah International Medical Research Centre, Jeddah, Saudi Arabia, was duly acquired prior to conducting this study (approval number: SP20/050/J, dated April 22, 2020). No names and Identities (IDs) were collected from the participants, and the data were stored within 64‑bit encrypted software on the work computer of the primary investigator that was not liable to be breached by nonauthorized persons.

Results

A total of 1,151 isolates were obtained from the BESTCare system in MNGHA, Jeddah, Saudi Arabia, between May 2016 and December 2019. These samples were categorized into age groups. Overall, 52.7% (n = 607) of these samples were collected from female patients, and 78.2% (n = 900) and 21.8% (n = 251) were collected from inpatients and outpatients, respectively. Data regarding patient demographics, hospital settings, and specimen types are displayed in Table 1.

    n=1151 %
Age      
  15–25 years 55 4.8
  26–35 years 40 3.5
  36–45 years 129 11.2
  46–55 years 107 9.3
  56–65 years 175 15.2
  66–75 years 232 20.2
  76–85 years 294 25.5
  86–95 years 101 8.8
  >95 years 18 1.6
Gender    
  Male 544 47.3
  Female 607 52.7
Status    
  Outpatient 251 21.8
  Inpatient 900 78.2
Diagnosis    
  Respiratory infection 568 49.3
  Urinary tract infection 583 50.7
Date of diagnosis  
  2016 174 15.1
  2017 352 30.6
  2018 371 32.2
  2019 254 22.1

Regarding specimen sources, 49.3% (n = 568) of the samples were obtained from respiratory specimens, 50.7% (n = 583) were obtained from urine specimens, and the sources of seven specimens were not documented; thus, the total number of specimens was 1,144 (Table 2). 

    n=1144 %
Specimen source  
  Urine 578 50.5
  Sputum 397 34.7
  Endotracheal aspiration 62 5.4
  Tracheal aspiration 51 4.5
  Nasal swab 21 1.8
  Urinary catheter 13 1.1
  MRSA culture 10 .9
  Bronchoalveolar lavage 5 .4
  Nasopharyngeal airway (NPA) 3 .3
  Bronchial biopsy 1 .1
  Bronchial wash 1 .1
  Pleural fluid 1 .1
  Tissue culture 1 .1

The top 10 most common causative agents of UTIs and RTIs were E. coli (26.4%; n = 304), K. pneumoniae (24.2%; n = 278), P. aeruginosa (16.9%; n = 194), Acinetobacter baumannii (8.4%; n = 97), MRSA (3.6%; n = 42), Enterococcus faecalis (3%; n = 35), S. aureus (2.9%; n = 33), Proteus mirabilis (2.1%; n = 24), Haemophilus influenzae (2%; n = 23), and S. pneumoniae (1.8%; n = 21) (Figure 1, Table 3).

Bacterial-composition:-comparison-between-common-bacterial-isolates-in-urinary-tract-infections-(UTIs)-and-respiratory-tract-infections-(RTIs) during-the-study-period.
  Bacteria n=1151 %
  Escherichia coli 304 26.4
  Klebsiella pneumoniae 278 24.2
  Pseudomonas aeruginosa 194 16.9
  Acinetobacter baumannii 97 8.4
  Methicillin-resistant Staphylococcus aureus 42 3.6
  Enterococcus faecalis 35 3.0
  Staphylococcus aureus 33 2.9
  Proteus mirabilis 24 2.1
  Haemophilus influenzae 23 2.0
  Streptococcus pneumoniae 21 1.8
  Serratia marcescens 18 1.6
  Stenotrophomonas maltophilia 16 1.4
  Enterobacter cloacae 9 .8
  Citrobacter koseri 8 .7
  Providencia stuartii 7 .6
  Enterobacter aerogenes 7 .6
  Enterococcus faecium 5 .4
  Burkholderia cepacia 5 .4
  Klebsiella oxytoca 4 .3
  Citrobacter freundii 2 .2
  Salmonella 2 .2
  Elizabethkingia meningoseptica 2 .2
  Alcaligenes faecalis 2 .2
  Serratia liquefaciens 1 .1
  Bacillus anthracis 1 .1
  Moraxella catarrhalis 1 .1
  Serratia fonticola 1 .1
  Morganella morganii 1 .1
  Staphylococcus capitis 1 .1
  Cedecea lapagei 1 .1
  Pseudomonas putida 1 .1
  Providencia rettgeri 1 .1
  Achromobacter xylosoxidans 1 .1
  Cronobacter sakazakii 1 .1
  Haemophilus parainfluenzae 1 .1
  Pantoea species 1 .1

The most common microbial causative agent of UTIs was E. coli (46.7%; n = 272), followed by K. pneumoniae (30.5%; n = 178), E. faecalis (6%; n = 35), P. aeruginosa (5.5%; n = 32), and P. mirabilis (2.2%; n = 13) (Table 4).

 Bacteria n=583 %
  Escherichia coli 272 46.7
  Klebsiella pneumoniae 178 30.5
  Enterococcus faecalis 35 6.0
  Pseudomonas aeruginosa 32 5.5
  Proteus mirabilis 13 2.2
  Acinetobacter baumannii 11 1.9
  Citrobacter koseri 6 1.0
  Enterobacter cloacae 5 .9
  Enterococcus faecium 5 .9
  Providencia stuartii 5 .9
  Enterobacter aerogenes 4 .7
  Serratia marcescens 3 .5
  Staphylococcus aureus 2 .3
  Stenotrophomonas maltophilia 2 .3
  Salmonella 2 .3
  Methicillin-resistant Staphylococcus aureus 1 .2
  Streptococcus pneumoniae 1 .2
  Haemophilus influenzae 1 .2
  Serratia fonticola 1 .2
  Citrobacter freundii 1 .2
  Cedecea lapagei 1 .2
  Pseudomonas putida 1 .2
  Pantoea species 1 .2

Furthermore, E. coli was most resistant to ampicillin (56.4%), followed by ceftriaxone (33.8%), ciprofloxacin (3.8%), amoxicillin (2.6%), and trimethoprim/sulfamethoxazole (1.7%; p = 0.014). Similarly, K. pneumoniae was most resistant to ampicillin (69.7%), followed by ceftriaxone (23.9%), amoxicillin/clavulanate (2.8%), amoxicillin (1.7%), and ciprofloxacin (0.6%; p < 0.001). Meanwhile, E. faecalis was most resistant to ciprofloxacin (28.6%), followed by ampicillin (21.4%), erythromycin and clindamycin (14.3%), and vancomycin (7.1%; p = 0.619). The P. aeruginosa isolates were most resistant to piperacillin/tazobactam (53.8%), followed by ciprofloxacin and ampicillin/sulbactam (15.4%) and cefazolin and trimethoprim/sulfamethoxazole (7.7%; p = 0.023). Finally, P. mirabilis was most resistant to ampicillin (53.8%), followed by ciprofloxacin (23.1%), nitrofurantoin (15.4%), and trimethoprim/sulfamethoxazole (7.7%; p = 0.860). The complete results are illustrated in Table 5 and Table 6. 

  Urinary tract infection bacteira (Resistant) Year of diagnosis p-value
  2016 2017 2018 2019  
    n=31 % n=81 % n=83 % n=39 %  
Escherichia coli                 0.550
  Ciprofloxacin 0 0.0 3 3.7 4 4.8 2 5.1  
  Ceftriaxone 13 41.9 30 37.0 23 27.7 13 33.3  
  Piperacillin/tazobactam 0 0.0 0 0.0 1 1.2 0 0.0  
  Amoxicillin-clavulanate 0 0.0 0 0.0 0 0.0 1 2.6  
  Cefazolin 0 0.0 1 1.2 0 0.0 0 0.0  
  Nitrofurantoin 0 0.0 0 0.0 1 1.2 0 0.0  
  Amoxicillin 1 3.2 4 4.9 1 1.2 0 0.0  
  Ampicillin 17 54.8 43 53.1 51 61.4 21 53.8  
  Trimethoprim/sulfamethoxazole 0 0.0 0 0.0 2 2.4 2 5.1  
    n=19 % n=42 % n=77 % n=38 %  
Klebsiella pneumoniae               0.209
  Ciprofloxacin 0 0.0 0 0.0 0 0.0 1 2.6  
  Ceftriaxone 2 10.5 13 31.0 18 23.4 9 23.7  
  Piperacillin/tazobactam 0 0.0 1 2.4 0 0.0 0 0.0  
  Amoxicillin-clavulanate 0 0.0 0 0.0 2 2.6 3 7.9  
  Nitrofurantoin 0 0.0 1 2.4 0 0.0 0 0.0  
  Amoxicillin 1 5.3 0 0.0 1 1.3 1 2.6  
  Ampicillin 16 84.2 27 64.3 56 72.7 24 63.2  
    n=5 % n=4 % n=2 % n=3 %  
Enterococcus faecalis               0.412
  Ciprofloxacin 3 60.0 0 0.0 1 50.0 0 0.0  
  Vancomycin 0 0.0 1 25.0 0 0.0 0 0.0  
  Erythromycin 0 0.0 1 25.0 0 0.0 1 33.3  
  Gentamicin 1 20.0 0 0.0 0 0.0 0 0.0  
  Nitrofurantoin 0 0.0 0 0.0 0 0.0 1 33.3  
  Clindamycin 1 20.0 1 25.0 0 0.0 0 0.0  
  Ampicillin 0 0.0 1 25.0 1 50.0 1 33.3  
    n=4 % n=5 % n=2 % n=2 %  
Pseudomonas aeruginosa               0.911
  Ciprofloxacin 1 25.0 0 0.0 0 0.0 1 50.0  
  Piperacillin/tazobactam 2 50.0 3 60.0 1 50.0 1 50.0  
  Cefazolin 0 0.0 0 0.0 1 50.0 0 0.0  
  Ampicillin/Sulbactam 1 25.0 1 20.0 0 0.0 0 0.0  
  Trimethoprim/sulfamethoxazole 0 0.0 1 20.0 0 0.0 0 0.0  
    n=3 % n=3 % n=4 % n=3 %  
Proteus mirabilis                 0.666
  Ciprofloxacin 1 33.3 0 0.0 2 50.0 0 0.0  
  Nitrofurantoin 0 0.0 1 33.3 0 0.0 1 33.3  
  Ampicillin 1 33.3 2 66.7 2 50.0 2 66.7  
  Trimethoprim/sulfamethoxazole 1 33.3 0 0.0 0 0.0 0 0.0  
Urinary tract infection bacteria (resistant)
Escherichia coli n %
  Ampicillin 132 56.4
  Ceftriaxone 79 33.8
  Ciprofloxacin 9 3.8
  Amoxicillin 6 2.6
  Trimethoprim/sulfamethoxazol 4 1.7
  Piperacillin/tazobactam 1 .4
  Amoxicillin/clavulanate 1 .4
  Cefazolin 1 .4
  Nitrofurantoin 1 .4
  Total 234 100.0
Klebsiella pneumoniae n %
  Ampicillin 123 69.9
  Ceftriaxone 42 23.9
  Amoxicillin/clavulanate 5 2.8
  Amoxicillin 3 1.7
  Ciprofloxacin 1 .6
  Piperacillin/tazobactam 1 .6
  Nitrofurantoin 1 .6
  Total 176 100.0
Enterococcus faecalis n %
  Ciprofloxacin 4 28.6
  Ampicillin 3 21.4
  Erythromycin 2 14.3
  Clindamycin 2 14.3
  Vancomycin 1 7.1
  Gentamicin 1 7.1
  Nitrofurantoin 1 7.1
  Total 14 100.0
Pseudomonas aeruginosa n %
  Piperacillin/tazobactam 7 53.8
  Ciprofloxacin 2 15.4
  Ampicillin/sulbactam 2 15.4
  Cefazolin 1 7.7
  Trimethoprim/sulfamethoxazol 1 7.7
  Total 13 100.0
Proteus mirabilis n %
  Ampicillin 7 53.8
  Ciprofloxacin 3 23.1
  Nitrofurantoin 2 15.4
  Trimethoprim/sulfamethoxazol 1 7.7
  Total   13   100.0  
Acinetobacter baumannii n %
  Piperacillin/tazobactam 9 90.0
  Ampicillin 1 10.0
  Total 10 100.0
Citrobacter koseri n %
  Piperacillin/tazobactam 2 33.3
  Amoxicillin/clavulanate 2 33.3
  Ciprofloxacin 1 16.7
  Cefazolin 1 16.7
  Total 6 100.0
Enterobacter cloacae n %
  Amoxicillin/clavulanate 5 100.0
Enterococcus faecium n %
  Ampicillin 4 80.0
  Nitrofurantoin 1 20.0
  Total 5 100.0
Providencia stuartii n %
  Ampicillin 3 60.0
  Ceftriaxone 2 40.0
  Total 5 100.0
Enterobacter aerogenes n %
  Amoxicillin/clavulanate 3 75.0
  Amoxicillin 1 25.0
  Total 4 100.0

Regarding the isolates from respiratory sources, the most frequently isolated pathogen was P. aeruginosa (28.5%), followed by K. pneumoniae (17.6%), A. baunmannii (15.1%), MRSA (7.2%), and E. coli (5.6%) (Table 7).

Bacteria n=568 %
  Pseudomonas aeruginosa 162 28.5
  Klebsiella pneumoniae 100 17.6
  Acinetobacter baumannii 86 15.1
  Methicillin-resistant Staphylococcus aureus 41 7.2
  Escherichia coli 32 5.6
  Staphylococcus aureus 31 5.5
  Haemophilus influenzae 22 3.9
  Streptococcus pneumoniae 20 3.5
  Serratia marcescens 15 2.6
  Stenotrophomonas maltophilia 14 2.5
  Proteus mirabilis 11 1.9
  Burkholderia cepacia 5 .9
  Enterobacter cloacae 4 .7
  Klebsiella oxytoca 4 .7
  Enterobacter aerogenes 3 .5
  Citrobacter koseri 2 .4
  Providencia stuartii 2 .4
  Elizabethkingia meningoseptica 2 .4
  Alcaligenes faecalis 2 .4
  Serratia liquefaciens 1 .2
  Bacillus anthracis 1 .2
  Moraxella catarrhalis 1 .2
  Morganella morganii 1 .2
  Citrobacter freundii 1 .2
  Staphylococcus capitis 1 .2
  Providencia rettgeri 1 .2
  Achromobacter xylosoxidans 1 .2
  Cronobacter sakazakii 1 .2
  Haemophilus parainfluenzae 1 .2

Regarding the 162 respiratory P. aeruginosa isolates, most (51.9%) were resistant to piperacillin/tazobactam, followed by ciprofloxacin (25%), ampicillin (10.6%), ampicillin/sulbactam (3.8%), and meropenem (2.9%; p < 0.001). Meanwhile, K. pneumoniae was most resistant to ampicillin (82.7%), followed by ceftriaxone (9.2%), piperacillin/tazobactam (7.1%), and amoxicillin (1%; p = 0.153). Finally, the A. baunmannii isolates were most resistant to piperacillin/tazobactam (52.6%; p = 0.520). Table 8 and Table 9 give details of respiratory infection bacterial resistence. 

Respiratory infection bacteria (Resistant)
Pseudomonas aeruginosa n %
  Piperacillin/tazobactam 54 51.9
  Ciprofloxacin 26 25.0
  Ampicillin 11 10.6
  Ampicillin/sulbactam 4 3.8
  Meropenem 3 2.9
  Imipenem 2 1.9
  Ceftazidim 2 1.9
  Cefepime 1 1.0
  Tigecycline 1 1.0
  Total 104 100.0
Klebsiella pneumoniae n %
  Ampicillin 81 82.7
  Ceftriaxone 9 9.2
  Piperacillin/tazobactam 7 7.1
  Amoxicillin 1 1.0
  Total 98 100.0
Acinetobacter baumannii n %
  Piperacillin/tazobactam 41 52.6
  Ampicillin 30 38.5
  Ciprofloxacin 4 5.1
  Meropenem 1 1.3
  Ceftriaxone 1 1.3
  Amoxicillin/clavulanate 1 1.3
  Total 78 100.0
Methicillin-resistant Staphylococcus aureus n %
  Cefazolin 8 72.7
  Clindamycin 2 18.2
  Piperacillin/tazobactam 1 9.1
  Total 11 100.0
Escherichia coli n %
  Ampicillin 16 59.3
  Ceftriaxone 10 37.0
  Amoxicillin 1 3.7
  Total 27 100.0
Staphylococcus aureus n %
  Clindamycin 4 40.0
  Erythromycin 3 30.0
  Trimethoprim/sulfamethoxazol 2 20.0
  Cefazolin 1 10.0
  Total     10     100.0    
Haemophilus influenzae n %
  Ciprofloxacin 1 50.0
  Ampicillin 1 50.0
  Total 2 100.0
Streptococcus pneumoniae n %
  Ceftriaxone 2 20.0
  Erythromyc...

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