Prepared by :
Dr Kushlani Jayatilleke, MBBS (Colombo), Diploma in Medical Microbiology, MD in Medical Microbiology,
Consultant Microbiologist, Consultant Microbiologist,
Sri Jayewardenepura General Hospital,
Honorary Senior Lecturer, Faculty of Medicine,
University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
Background:
Antimicrobial resistance (AMR) is a global public health and development threat. It is estimated that bacterial AMR was directly responsible for 1.27 million global deaths in 2019 and contributed to 4.95 million deaths. (1) In addition to death and disability, AMR has significant economic costs. The World Bank estimates that AMR could result in US$ 1 trillion additional healthcare costs by 2050, and US$ 1 trillion to US$ 3.4 trillion gross domestic product (GDP) losses per year by 2030 (2)
To strengthen the knowledge and evidence base through surveillance and research is one of the 5 objectives identified in the global action plan on antimicrobial resistance of World Health Organization (WHO). (3)
History:
In Sri Lanka, first multi centre AMR surveillance was started as the Antibiotic Resistance Surveillance Project (ARSP) which produced data from blood culture isolates by the Sri Lanka College of Microbiologists (SLCM) in a few selected hospitals in 2009 and was expanded to all hospitals with consultant microbiologists by 2013. SLCM proposed and implemented a system to improve supplies and standards in the microbiology laboratories to make the data meaningful. The data of the first phase of this project was published as an article in 2011. (4)
In addition another multi centre project on AMR was established as a collaborative project of SLCM and Ministry of Health (MoH), in 2011 as the National Laboratory Based Surveillance of Antimicrobial Resistance and the data of urine culture isolates were analysed and published in 2016. (5)
National Antimicrobial resistance Surveillance for human health sector:
In 2016 the National Strategic Plan for Combating Antimicrobial Resistance in Sri Lanka 2017 – 2022 was published and as an activity of this the National AMR surveillance of human sector was strengthened by the AMR focal point in MoH along with the SLCM. The surveillance was initially planned to collect data from 25 sentinel sites that will cover the whole island. Data pertaining to antimicrobial resistance was collected from these hospitals using the ‘WHONET’ software specifically designed to collect data on antimicrobial resistance.
The National Protocol for Antimicrobial resistance Surveillance for human health sector was developed and data collection was initiated by June 2018. Data is analyzed quarterly and a committee for data analysis and interpretation was established consisting of Health Administrators, Microbiologists and Epidemiologists and Medical officers having qualifications in Bio informatics. Sri Lanka became a member of the GLASS in 2018 and participated for the
data call in 2019 for the first time.
The pathogens from the identified specimens with the antibiotics of AST results to be reported were identified as follows:
| Specimens | Pathogen | Antibiotics of AST results to be reported |
|---|---|---|
| Blood | Escherichia coli | cefotaxime / ceftriaxone, ciprofloxacin, Meropenem/ Imipenem |
| Klebsiella pneumoniae | cefotaxime / ceftriaxone, ciprofloxacin, Meropenem/ Imipenem |
|
| Acinetobacter species | Meropenem/ Imipenem | |
| Urine | Escherichia coli | cefotaxime / ceftriaxone, ciprofloxacin, Meropenem/ Imipenem |
| Klebsiella pneumoniae | cefotaxime / ceftriaxone, ciprofloxacin, Meropenem/ Imipenem |
|
| Pseudomonas aeruginosa | Meropenem/ Imipenem | |
| Enterococcus faecalis and E. faecium | Vancomycin (confirm resistance by MIC) | |
| Faeces | Salmonella spp. | cefotaxime / ceftriaxone, ciprofloxacin |
| Shigella species | ciprofloxacin | |
| Urethral and Cervical swabs |
Neisseria gonorrhoeae | ceftriaxone |
Blood samples- All clinically significant culture isolates as determined by the Consultant Microbiologist.
Urine samples – All positive isolates with a ≥105colony count from midstream urine samples
Faeces- All positive culture isolates
Urethral and cervical swabs-All positive culture isolates
Global Antimicrobial Resistance and Use Surveillance System (GLASS) (6):
Sri Lanka was enrolled for GLASS AMR data submission in 2018.
According to the GLASS report of 2020 data from 17 sentinel sites from Sri Lanka were reported on the GLASS platform, in 2019 data call. All the identified laboratories for this surveillance system participates in the External Quality Assurance (EQA) programme conducted by Medical Research Institute, Colombo for bacterial culture and AST,
The 70-100% data submission was achieved on AST, gender and age for Acinetobacter spp., E. coli, K. pneumoniae, Salmonella spp and S. pneumoniae from blood cultures E. coli and K. pneumoniae in urine and Salmonella spp. in stool samples had >70% AST and age data but <70% gender data.
The total bacteriologically confirmed blood stream infections reported in 2021 were 1628 (74.8 per million population). AST data of Pseudomonas aeruginosa and Enterococcus faecalis and E. faecium (in urine), Shigella spp. and N. gonorrhoeae were not available.
With the improved sanitation, isolation of Shigella spp. is probably rare but we should improve the surveillance by submitting data of other important pathogens. A method should be planned to submit AST data of N. gonorrhoeae. by collaborating with the National STD AIDS campaign laboratory. Vancomycin resistant Enterococcus faecalis and E. faecium and Pseudomonas aeruginosa are identified in the surveillance protocol as urine isolates. This may be difficult since urine isolates are not usually identified into species level at all times. If these 3 organisms are analysed from blood culture isolates, we may get some data on these.
Majority of the data were from > 5 year age group. This may be due to the fact that the neonatal care is good in Sri Lanka and children are less likely to have bacteraemia and thus sepsis and bacteraemia in neonates and < 5 year age group is less. We can plan to include data from more hospitals with paediatric and neonatal care to improve the representation.
Blood culture isolates:
Escherichia coli:
Total BCIs
(2018 - 2021)
n = 1972
The table shows AST coverage for third-generation cephalosporins in E. coli overall, and the distribution of bacteriologically confirmed infections (BCIs) with AST by patient age group. Testing coverage is calculated by taking the maximum number of BCIs with AST results for any of the third-generation cephalosporins under surveillance. Percentages displayed in the "total" column, are calculated as the number of BCIs with AST results each year out of the total BCIs due to E. coli in the same year. Total BCIs with AST include observations where the age of the patient is unknown.
In 2019 only 74.5% were reported with AST which could be a mistake in data or may be due to non availability of antibiotic discs testing was not performed. We have managed to improve this
by 2021 to 97.9%.
Resistance to third-generation cephalosporins is calculated by taking the maximum resistance value identified from individual antibiotics, where more than one antibiotic was tested. The denominator of the resistance percentage calculation may thus differ from the number displayed in the testing coverage table.
Percentages are calculated considering total BCIs with AST for the relevant antibiotic/s. Observations based on < 10 BCIs with AST, are excluded from the plot (not shown).
It is encouraging to see a downward trend of % resistance for 3rd generation cephalosporins (3GC) in E. coli. This may be due to the actions taken by the Sri Lankan authorities and professionals by implementing the National Strategic Plan for combating antimicrobial resistance.
All antibiotics tested for E coli in blood cultures in 2021:
Ampicillin resistance is > 80% and cannot be considered as a useful antibiotic for E coli. Susceptibility testing for this antibiotic may not be worth for E coli. Resistance to fluoroquinolones (levofloxacin and ciprofloxacin) and cotromoxazole is very high (around 60%). Resistance to 3rd generation cephalosporins (cefotaxime and ceftriaxone) is also high being 57% in 2021. Resistance rates to beta lactam/beta lactamase combinations such as amoxicillin/ clavulanic acid and piperacillin/tazobactam, which are commonly used to treat patients in Sri Lanka, are not reported in this data since they were not identified in the surveillance protocol.
The resistance to 3rd generation cephalosporins (3GC) were further analysed. Three antibiotics were considered for this analysis. They are cefotaxime, ceftriaxone and ceftazidime which were tested and reported for 449, 102 and 206 isolates respectively. The resistance to each antibiotic were reported as 57%, 50% and 51% respectively for cefotaxime, ceftriaxone and ceftazidime.
This discrepancy could be due to the differences in centres which report these antibiotics. We can improve this by testing for a particular 3GC in all centres. In CLSI 2024 ceftriaxone is recommended for direct AST reporting of blood cultures and therefore it is convenient that all laboratories use ceftriaxone discs rather than cefotaxime discs for AST.
Meropenem resistance in E coli in blood cultures was 10.6% which is very high compared to countries such as the UK (0%) and Switzerland (0.04%). Therefore we should be careful not to misuse or overuse carbapenems as this group of antibiotics are very useful to treat life threatening infections due to antibiotic resistant bacteria. I think we should only use carbapenems guided by the ABST in serious infections and/or sepsis.
Klebsiella pneumoniae :
Total BCIs= n = 320
275 Klebsiella pneumoniae isolates from blood cultures were tested for fluoroquinolone resistance using ciprofloxacin and 72% were resistant. 3rd generation cephalosporin resistance was tested using cefotaxime, ceftriaxone and ceftazidime discs/MIC. 267,60 and 226 isolates were tested for cefotaxime, ceftriaxone and ceftazidime respectively. Resistance to cefotaxime, ceftriaxone and ceftazidime were 77%, 80% and 72% respectively. Here also the Ceftriaxone was tested for a lesser number of isolates. 267 isolates were tested for meropenem susceptibility and 48% were resistant.
Staphylococcus aureus :
Total BCIs
(2019 - 2021)
n = 1454
Though the S. aureus data was submitted due to a technical issue it was not shown on GLASS data of 2018. In 2019, 2020 and 2021 interpretable AST for methicillin resistance in S aureus as a percentage from the total number of S aureus blood culture isolates were 53.1 %, 55.5% and 51.6% respectively. Testing coverage is calculated by taking the maximum number of BCIs with AST results for oxacillin and/or second-generation cephalosporins (that is, cefoxitin). The coverage of AST is low here probably because some laboratories may not have entered the susceptibility for oxacillin and/or cefoxitin, but may be entered as cloxacillin etc. This has to be improved in the future when entering data for surveillance.
According to this data, % of MRSA in Staphylococcus aureus bacteraemia is also slowly reducing over the years. In 2021 the MRSA was 47.3%.
Acinetobacter spp. :
Only 142 isolates were reported and meropenem susceptibility data was available for 102 and 63
(61.8%) were resistant.
Salmonella spp.:
Only 12 Salmonella spp. were reported from blood cultures and 11 had interpretable AST. All were susceptible to cefotaxime.
Comparison of antibiotic resistance with other countries:
Here I have compared the 3GC and meropenem resistance in E coli and Klebsiella pneumoniae in BCI with positive blood cultures of Sri Lanka with the UK and Switzerland in 2021.
This shows how high the antibiotic resistance rates in Sri Lanka are, when compared to countries like the UK and Switzerland which have good antimicrobial stewardship and infection prevention and control practices implemented in the community as well as in the healthcare settings.
Urine culture isolates:
Escherichia coli
Total BCIs
n = 1733
Of the 1733 BCI in urine, interpretable AST for 3rd generation cephalosporins was available with cefotaxime in 1311 and with ceftriaxone only in 391. The resistance to cefotaxime ws 44% while for Ceftriaxone was 40%.
Interpretable AST for carbapenem resistance was available with meropenem in 1099 and with imipenem in only 429 BCIs. Resistance rate was 10% for imipenem while only 5% for meropenem. This discrepancy in % resistance in E coli is probably due to the testing policies in different laboratories. Some laboratories have a practice of testing AST for carbapenems only if they are resistant to first line antibiotics, especially in non-blood cultures. This means that these laboratories will have a higher resistance rate since their testing is from a more resistant population
i.e.,first line AST resistant population. The AST with imipenem and meropenem are from different laboratories and these testing policies may affect the resistance rates. Therefore in future the laboratories who supply data to the national surveillance should be advised to test carbapenems for all isolates with significant bacteriuria.
Conclusions and recommendations:
- By looking at the laboratory based data of Sri Lanka in the GLASS, it is evident that the resistance rates to most antibiotics are very high compared to some countries with good prescription control and infection prevention and control. Antibiotic stewardship programme in the community as well as in the healthcare institutions along with good infection prevention and control practices should be strengthened.
- Though the resistance to 3GCs is high in uropathogens such as E coli and Klebsiella pneumoniae, empirical antibiotic treatment with carbapenems is not recommended unless the patient is septic. (7)
- It is encouraging to see the downward trend of resistance in important pathogens such as E.coli and Staphylococcus aureus over the years, probably due to the better awareness on AMR and implementation of National Strategic Plan for combating AMR in Sri Lanka.
- The spectrum of pathogens on which AMR data is submitted need to be expanded.
- AMR surveillance should be improved to uniform testing protocols using the same discs or MIC and reporting appropriately and also to improve testing strategies such as testing all bacteriologically confirmed isolates with all antibiotics in the recommended panel. The regular supply of consumables to the laboratories to carry out the standard testing is crucial.
- Should discuss and improve the national AMR surveillance by including AST data of more organisms such as Pseudomonas aeruginosa and Enterococcus faecalis and E. faecium, Shigella spp. and N. gonorrhoeae.
- At laboratory level, checking the data entered to the WHONET by a technically competent second person or to arrange export of data which had been technically evaluated for reporting from the laboratory information system if available, will minimise errors of data entry.
- Antimicrobial consumption (AMC) data is currently not available for Sri Lanka in the GLASS platform. National Strategic plan implementation committee should register and submit AMC data of Sri Lanka to GLASS platform.
References:
- Antimicrobial Resistance Collaborators. (2022). Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet; 399(10325): P629-655. DOI: https://doi.org/10.1016/S0140-6736(21)02724-0
- Drug-Resistant Infections: A Threat to Our Economic future (March 2027) https://www.worldbank.org/en/topic/health/publication/drug-resistant-infections-a-threat-to-our-economic-future
- Global action plan on antimicrobial resistance; World Health Organization, who.int
- P Chandrasiri, JP Elwitigala, G Nanayakkara, S Chandrasiri, G Patabendige, L Karunanayaka, J Perera, P Somaratne, K Jayathilleke; A multi centre laboratory study of Gram negative
bacterial blood stream infections in Sri Lanka; Ceylon Medical Journal 2013; 58: 56-61; http://dx.doi.org/10.4038/cmj.v58i2.5680 - SK Jayatilleke, G Patabendige, M Dassanayake, GKD Karunaratne, J Perera, RRDP Perera, WRPLI Wijesooriya, NP Sunil-Chandra, J Kottahachchi, D Athukorala, T Dissanayake;Analysis of urine culture isolates from seven laboratories of Sri Lanka: National Laboratory Based Surveillance of Sri Lanka College of Microbiologists in 2014; Sri Lankan Journal of Infectious Diseases; Volume: 6 Issue: 1; 17-24; http://dx.doi.org/10.4038/sljid.v6i1.8105
- Global Antimicrobial Resistance and Use Surveillance System (GLASS); https://worldhealthorg.shinyapps.io/glass-dashboard/_w_b75d56dd/_w_588b29c4/#!/amr
- Perera YK, Chulasiri PU, Jayatilleke SK; Prevalence, Phenotypes of Beta Lactamase and Clinical Response to Empirical Therapy of Urinary Tract Infections Caused by Third Generation Cephalosporin Resistant Enterobacteriaceae in a Tertiary Care Hospital, Sri Lanka; oral presentation with abstract publication, 14th International Symposium on Antimicrobial Agents and Resistance 2024 /Annual Conference of the Korean Society for Antimicrobial Therapy; April 8 - 10, 20
