|Year : 2020 | Volume
| Issue : 1 | Page : 137
Methodology and early results of the first surveillance program on prevention and control of antimicrobial resistance in Isfahan, Iran: The IAS-I study
Sayed Nasser Mostafavi1, Soodabeh Rostami2, Behrooz Ataei1, Sina Mobasherizadeh2, Azam Cheraghi3, Somayeh Haghighipour1, Samereh Nouri4, Arezoo Pourdad5, Parisa Ataabadi5, Naser Almasi6, Leila Heidary6, Kourosh Naderi6, Setareh Korangbeheshti6, Shiva Navabi7, Laleh Masssah7, Zohreh Norouzi7, Mehrnoush Bakhtiyaritabar7, Saeed Moayednia4, Dariush Shokri2, Mahin Mikhak6, Majid Rahmani7, Mohammad Hashemi8, Reza Etminani3, Nasrin Ahmadi9, Mahboubeh Akhlaghi10, Roya Kelishadi11
1 Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Nosocomial Infection Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Hospitals Supervision and Accreditation, Vice-Chancellery for Clinical Affairs, Isfahan University of Medical Sciences, Isfahan, Iran
4 Department of Microbiology, Clinical Laboratory of Alzahra Medical Center, Isfahan, Iran
5 Alzahra Medical Center, Isfahan University of Medical Sciences, Isfahan, Iran
6 Department of Microbiology, Clinical Laboratory of Dr. Shariati Hospital, Isfahan Social Security Organization, Isfahan, Iran
7 Department of Microbiology, Clinical Laboratory of Dr. Gharazi Hospital, Isfahan Social Security Organization, Isfahan, Iran
8 Cardiovascular Department, Interventional Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
9 Vice-Chancellery for Clinical Affairs, Isfahan Social Security Organization, Isfahan, Iran
10 Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
11 Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
|Date of Submission||25-May-2019|
|Date of Acceptance||14-Oct-2019|
|Date of Web Publication||03-Sep-2020|
Soffeh Street, Alzahra Hospital, Research Comprehensive Laboratory, Infectious Diseases and Tropical Medicine Research Center, Isfahan
Source of Support: None, Conflict of Interest: None
Background: Isfahan Antibiotic Resistance Surveillance System-1 has been instituted in Isfahan, Iran to construct a project for surveillance of clinically significant bacteria, and to help raise a logic regional stewardship program for prevention and control of disseminating-resistant organisms. Methods: During March 2016 to March 2018, an antibiotic resistance surveillance system was designed and implemented by Isfahan Infectious Diseases and Tropical Medicine Research Center. The surveillance program was implemented in three general hospitals in Isfahan. In addition to the routine microbiology data, clinical data (differentiation between true infections and contamination, healthcare-associated infections (HCAI) and community-acquired infections (CAI), as well as determination of the infection site) were obtained and analyzed by WHONET software. Results: During a 2-year period, from 7056 samples that revealed growth of bacteria, 3632 (51.5%) isolates were detected as contamination and 3424 (48.5%) true bacterial isolates were identified. Of these, about 32% of isolates were recognized as HCAI. Totally, the most recognized infections were urinary tract infection, bloodstream infection and skin and soft tissue infections. In patients with HCAIs, 70% of isolates were gram negative and in patients with CAIs 73% isolates were gram negative bacteria. Conclusions: The strength of the project is gathering enough clinical information in addition to microbiologic data, which would increase application of the results for empiric treatment and prevention of the infectious diseases in clinical settings.
Keywords: Bacteria, drug resistance, epidemiology, Iran, methods
|How to cite this article:|
Mostafavi SN, Rostami S, Ataei B, Mobasherizadeh S, Cheraghi A, Haghighipour S, Nouri S, Pourdad A, Ataabadi P, Almasi N, Heidary L, Naderi K, Korangbeheshti S, Navabi S, Masssah L, Norouzi Z, Bakhtiyaritabar M, Moayednia S, Shokri D, Mikhak M, Rahmani M, Hashemi M, Etminani R, Ahmadi N, Akhlaghi M, Kelishadi R. Methodology and early results of the first surveillance program on prevention and control of antimicrobial resistance in Isfahan, Iran: The IAS-I study. Int J Prev Med 2020;11:137
|How to cite this URL:|
Mostafavi SN, Rostami S, Ataei B, Mobasherizadeh S, Cheraghi A, Haghighipour S, Nouri S, Pourdad A, Ataabadi P, Almasi N, Heidary L, Naderi K, Korangbeheshti S, Navabi S, Masssah L, Norouzi Z, Bakhtiyaritabar M, Moayednia S, Shokri D, Mikhak M, Rahmani M, Hashemi M, Etminani R, Ahmadi N, Akhlaghi M, Kelishadi R. Methodology and early results of the first surveillance program on prevention and control of antimicrobial resistance in Isfahan, Iran: The IAS-I study. Int J Prev Med [serial online] 2020 [cited 2021 Apr 17];11:137. Available from: https://www.ijpvmjournal.net/text.asp?2020/11/1/137/294318
| Introduction|| |
Antimicrobial resistance (AMR) is one of the most important international problems. World Health Organization (WHO) highlighted the significance of this statement by naming the 2011 World Health Day as “Antibiotic resistance: no action today, no cure tomorrow.” This organization recognized surveillance programs on prevention of AMR as essential necessities to tackle this threat. To date, several antimicrobial surveillance systems have been initiated; however in developing nations few surveillance programs have been established.,
Multiple studies have been conducted on AMR in different regions of Islamic republic of Iran. These researches showed extraordinary resistance among bacterial strains.,,,,,,, However, these investigations had been performed in limited area, sometimes in small number of the organisms, and with different methodologies that make the results unsuitable for decision about the best empiric treatments for infections in the country. Therefore, there is a need for an active surveillance of clinically significant bacteria for better recognition and prevention of antibiotic resistance.
The aim of present survey was to implement a regional surveillance program for determining antibiotic resistance in bacteria isolated from clinical samples. In addition, it targeted to differentiate true infections from contamination, healthcare-associated infections (HCAI) from community-acquired infections (CAI), as well as to determinate the infection site.
| Methods|| |
Initial research development and design
In May 2015, to design a local AMR surveillance system a work group organized in Isfahan Infectious Diseases and Tropical Medicine Research Center (IDRC). This group established a program entitled “Isfahan Antibiotic resistance Surveillance system-1 (IAS-1)” and subsequently considered as surveillance system executive committee. Chairman of the research center was the head of committee. Committee members included: a representative of Research and technology, Food and Drug, Clinical affairs and Health vice-chancelleries of Isfahan University of Medical Sciences (MUI) and four faculty members of infectious diseases department. The main function of executive committee was to plan, implement, facilitate, and debug performance of the project. After the third meeting, the executive committee decisions were as follow: establishment of two main operational committees including: performing and scientific committee, and performance of the project in three major general hospitals of the Isfahan city during March 2016 to March 2018 as the first phase of surveillance program (Ethical approval and Project No: 194042). Performing committee was composed of three infection control physicians, four infection control nurses, three microbiologists, and one chief coordinator. The main function of the performing committee was to collect and report microbiologic and clinical data. Scientific committee was consisting of three infectious disease specialists, one pediatric infectious disease subspecialist, and two medical bacteriology PhDs. The scientific committee was responsible for preparing guidelines and interpretation of final results.
Procedure and measurements
Place of the surveillance
Geographically, the area under surveillance was the city of Isfahan, as the capital of Isfahan Province, located in center of Islamic Republic of Iran. The population under surveillance included the peoples who live in Isfahan (according to the census in 2016, 2,243,249 peoples).
In 2016, Isfahan has five general hospitals including: three educational general hospitals under the supervision of Isfahan University of Medical Sciences and two general hospitals under the supervision of Iranian Social Security Organization. In this survey, three hospitals (Alzahra hospital, Dr. Shariati hospital, and Dr. Gharazi hospital) were candidate to participate. Clinical microbiology laboratories of these referral medical centers achieved an approved Quality Credit from the Vice-Chancellor of Iranian Ministry of Health, Treatment, and Medical Education and were also two of them (Alzahra and Dr. Shariati hospitals) collaborators of WHO in reporting of susceptibility of microorganisms in Global AMR Surveillance System (GLASS) program.
The Al-zahra hospital, which was the only tertiary care referral hospital in the Isfahan, included 318 medical, 300 surgical, 10 kidney transplant, and 115 intensive care unit (ICU) beds. The laboratory of the hospital received approximately 8000 specimens for bacterial culture per year. Dr. Shariati and Dr. Gharazi hospitals totally included 236 medical, 215 surgical and 19 ICU beds. The laboratories of these hospitals received approximately 6000 specimens for bacterial culture per year.
Data collection and reporting
During March 2016 to March 2018, all bacteria isolated from all clinical samples submitted to three hospital microbiology laboratories were enrolled to survey. Clinical sampling procedures were accomplished by experienced nurses in medical wards and sometimes by surgeons in operational rooms. National guidelines were applied for collecting and handling of the specimens. Respiratory samples that were collected with methods other than bronchoalveolar lavage and biopsy were excluded. Basic demographic information including: hospital record number, age, sex, and admission ward were collected on each patient.
Bacterial isolation, identification, and antibiotic susceptibility testing were performed using conventional methods and recommendations of Clinical Laboratory and Standards Institute (CLSI) guidelines 2016 through 2018. In all participated hospitals, the same dehydrated antibiotic discs (Mast, UK) and if necessary minimum inhibitory concentration (MIC) test strip (Liofilchem, Italy) were applied.
For data collection, we used the WHONET software which has multifunctional analysis ability and was produced by WHO for routine microbiology laboratory data management. For accumulation of clinical results, we added three items for determination of contaminated samples, source of the infection (healthcare-associated versus community-acquired), and site of the infection (urinary tract, sepsis, blood stream …).
In each participated hospital, after obtaining microbial culture results, the infection control team made difference between true infection and contamination, HAI and CAI and recognized the infection site. This was made by practical guidelines which prepared by scientific committee with regard to previous literature [Box 1], [Box 2] and [Supplement Table 1].,, Finally, all microbiology and clinical data were recorded in WHONET software by the laboratory staff that was responsible for data record. At the end of each month, the WHONET files were sent to IDRC. There, all WHONET files from participated hospitals were merged and analyzed.
The study protocol was approved by the Institutional Review Board of Isfahan University of Medical Sciences (Approval number: 194042). As the subject of the surveillance was the bacteria, it was not necessary to obtain the patients' consent.
| Results|| |
From March 2016 to March 2018, 24 WHONET files (1 file/per month) were received from Dr. Shariati and Dr. Gharazi hospitals and 17 WHONET files (1 file/per month) from Alzahra hospital. Urine culture information was reviewed and analyzed only in the first year due to the large number of samples. Totally, data from 29,176 clinical samples were analyzed. Of these, about 21654 (74%) samples showed negative results and 466 (2%) samples revealed growth of fungi. In 7056 samples that revealed growth of bacteria, 3632 (51.5%) isolates were detected as contamination and excluded from the study. From 3424 remaining isolates that included in the study, 2327 (68%) isolates were isolated from CAIs and the remaining ones (1097; 32%) from HCAIs. In patients with confirmed CAIs and HCAIs, 1193 (51%) and 589 (54%) were males, 286 (12%) and 118 (10%) were ≤20 years, respectively.
In patients with CAI, most samples were received from emergency room (55%), internal medicine (17%), surgery (8%), ICU (4%), and other wards (17%), whereas in the HCAIs, most infections occurred in ICU (34%), internal medicine (26%), surgery (12%), emergency room (10%), and other wards (18%).
The most recognized infections in CAIs were urinary tract infection (50%), bloodstream infections (31%), and skin and soft tissue infections (10%). In patients with HCAIs bloodstream infections (36%) and urinary tract infections (26%) were the most diagnosis followed by surgical site infections (18%), pneumonia (6%), and meningitis (6%).
In patients with CAIs, 1707 (73%) isolates were gram negative bacteria and the most common gram negative strains were Escherichia coli (62%) [Table 1]. Overall, they were more susceptible to colistin (100%), imipenem (93.2%), amikacin (86.3%), meropenem (85.6%), and nitrofurantoin (83%) [Table 2]. The most common gram positive isolates from CAIs were Staphylococcus aureus (37%) [Table 1]. The more sensitivity of gram positives was to amikacin (96.9%), teicoplanin (89.9%), vancomycin (89.9%), nitrofurantoin (88.9%), linezolid (88.5%), rifampin (88.3), and gentamicin (72.6%) [Table 3].
|Table 2: Susceptibility pattern of gram negative bacteria isolated from CAIs and HCAIs|
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|Table 3: Susceptibility pattern of gram positive bacteria isolated from CAIs and HCAIs|
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In patients with HCAIs, 766 (69.8%) isolates were gram negative. The most common gram negative strains were Klebsiella pneumoniae (30%) [Table 1]. In total, gram negatives were more susceptible to colistin (100%), nitrofurantoin (67.3%), imipenem (66.2%), and amikacin (55.7%) [Table 2]. The most common gram positive isolates from HCAIs were enterococcus spp (43%) [Table 1]. Higher sensitivity of gram positive organisms was to linezolid (97%), rifampin (86.7%), amikacin (81.8%), nitrofurantoin (75%), and vancomycin (69.5%), respectively [Table 3].
| Discussion|| |
In this paper, we presented design, methodology, and early results of IAS-1 program. This AMR surveillance program seems to be the first project in which combined clinical data to microbiologic results. To date, many AMR surveillance programs have been implemented around the world. They are different in various factors including: geographic location, priority pathogens and specimens, type of information, and source of infection (nosocomial/outpatient).,,,
One of the most comprehensive programs is SENTRY program which includes 30 medical centers in the United States, 8 in Canada, 10 in South America, and 24 in Europe. The most important advantages of the program are multinational coverage, low workload for participating laboratory, and testing of isolates in a central reference laboratory. The most notable disadvantage is delay in reporting of data.,
European AMR Surveillance System is another multinational surveillance that was organized in 375 centers in 15 European countries on Streptococcus pneumoniae and Staphylococcus aureus isolates. The advantages of the program are good external quality and timeliness in reporting of information. The disadvantage is relatively great workload for participating laboratory.
Despite these relatively high qualities surveillance programs that were established in high income countries, few high quality surveillance programs were implemented in middle or low income countries,, The most prominent limitation in these areas is the low yield of isolation of significant bacteria in microbiological laboratories. In addition, the rates of antibiotic pretreatment in these communities are high which will decrease the yield of positive blood cultures. Funding source is another concern in these countries.
However, many surveillance programs have been initiated in these areas. Some of these systems include: Central Asian and Eastern European Surveillance (CAESAR) in 17 middle income and 3 high income countries, and AMR national surveillance systems in Viet Nam, Nepal, and China.
In 2015, WHO launched Global AMR Surveillance System (GLASS). AMR data for nine microorganisms are registered in the surveillance. The data are collected from specimens that have been sent routinely to laboratories for clinical purposes. For data entry, an automated computer software (WHONET) was developed and adapted. Laboratories in more than 90 countries including Islamic Republic of Iran are included in GLASS.
Our surveillance was performed in three laboratories in Isfahan, Iran which two of them are collaborated with GLASS and have qualification certificate from Iranian government for performing standard microbiologic tests. In our surveillance, to optimize the use of information in prevention and control of antibiotic resistance in pathogen bacteria, we added more clinical data to microbiologic data. Added clinical data included: differentiation between contamination from true infection, determination of site of infection, and clarification of nosocomial from CAIs. It could be a good model of combining antibiotic resistant surveillance results and patient's clinical information for planning preventive measures in clinical settings.
The project was the first AMR surveillance experience in the area and had some limitations. First, we collected antibiotic resistance data of pathogens which isolated from patients admitted in three major hospitals and these results could not be representative of the total antibiotic resistance in area can lead to high estimation of the antibiotic resistance rates. In addition, we relied on data which obtained from routine medical microbiology tasks without external quality control in a reference laboratory. However, it should be acknowledged that all these laboratories have received quality certificate from Iranian Ministry of Health and the methods of microbiological tests were the same and frequently checked by supervisor of the surveillance. The third limitation was delay in reporting data. The results were sent to the IDRC at the end of each month. However, some laboratories send their data with delay. Using the Web-based systems could be helpful in second phase of the project to achieve on time distribution of data.
The forth limitation was inadequate project budget. Our surveillance was funded through a research project planned for 2 years. For the second phase of surveillance a sustainable source of funding will be required. Finally, the fifth limitation was the high workload for laboratory personnel, which would increase the cost of the surveillance program and decrease timeliness of reporting of information.
In spite of these limitations, our study is the first surveillance in the region that can provide valuable information on the antibiotic resistance of a wide range of pathogens along with patient's clinical data and it can be a proper guide for clinicians, microbiologists, infection control practitioners and public-health authorities.
| Conclusion|| |
We described design and methodology of IAS-1 surveillance project in this paper. The strength of the project is gathering enough clinical information in addition to microbiologic data that would increase the application of the results for empiric treatment of the infectious diseases and planning of infection control programs in clinical settings. However, our program faces some limitations in representativeness of samples, external quality assessment of data, timeliness of reporting, sustained funds, and additional workload for health professionals, and will be improved in further phase.
We forward our sincere acknowledgments to the large team that cooperated in three collaborative medical centers. We would like to thank all organizations contributed to this survey.
Financial support and sponsorship
This work was supported by Isfahan University of Medical Sciences with grant number: 194042.
Conflicts of interest
There are no conflicts of interest.
| References|| |
World Health Organization. Antimicrobial Resistance: Global Report on Surveillance.WHO; 2014.
Vernet G, Mary C, Altmann DM, Doumbo O, Morpeth S, Bhutta ZA, et al
. Surveillance for antimicrobial drug resistance in under-resourced countries. Emerg Infect Dis 2014;20:434-41.
Dadashi M, Nasiri MJ, Fallah F, Owlia P, Hajikhani B, Emaneini M, et al
. Methicillin-resistant Staphylococcus aureus
(MRSA) in Iran: A systematic review and meta-analysis. J Glob Antimicrob Resist 2018;12:96-103.
Alizade H. Escherichia coli
in Iran: An overview of antibiotic resistance: A review article. Iran J Public Health 2018;47:1-12.
Heidary M, Nasiri MJ, Dabiri H, Tarashi S. Prevalence of drug-resistant Klebsiella pneumoniae in Iran: A review article. Iran J Public Health 2018;47:317-26.
Emaneini M, Hosseinkhani F, Jabalameli F, Nasiri MJ, Dadashi M, Pouriran R, et al
. Prevalence of vancomycin-resistant enterococcus in Iran: A systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis 2016;35:1387-92.
Mostafavi N, Bighamian M, Mobasherizade S, Kelishadi R. Resistance of Shigella strains to extended-spectrum cephalosporins in Isfahan province. Med J Islam Repub Iran 2016;30:428.
Khademi F, Poursina F, Hosseini E, Akbari M, Safaei HG. Helicobacter pylori
in Iran: A systematic review on the antibiotic resistance. Iran J Basic Med Sci 2015;18:2-7.
Karimian M, Kermani R, Khaleghi M, Kelishadi R, Ataei B, Mostafavi N. Antibiotic susceptibility patterns of isolates from children with urinary tract infection in Isfahan, Iran: Impact on empirical treatment. J Glob Antimicrob Resist 2017;9:3-7.
Farid GA, Moghaddam AB, Bojdy A. Nosocomial pneumonia in patients admitted to the intensive care unit of a tertiary care center in Mashhad, Northeast of Iran; An Etiologic Survey. Arch Clin Infect Dis 2018;13:e64239.
World Health Organization. Global Antimicrobial Resistance Surveillance System: Manual for Early Implementation. WHO; 2015.
Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; 22nd
informational supplement. 2015, CLSI M100-S25.
Hall KK, Lyman JA. Updated review of blood culture contamination. Clin Microbiol Rev 2006;19:788-802.
Lee CC, Lin WJ, Shih HI, Wu CJ, Chen PL, Lee HC, et al
. Clinical significance of potential contaminants in blood cultures among patients in a medical center. J Microbiol Immunol Infect 2007;40:438-44.
Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008;36:309-32.
Monnet DL. Toward multinational antimicrobial resistance surveillance systems in Europe. Int J Antimicrob Agents 2000;15:91-101.
Bax R, Bywater R, Cornaglia G, Goossens H, Hunter P, Isham V, et al
. Surveillance of antimicrobial resistance—what, how and whither? Clin Microbiol Infect 2001;7:316-25.
Fluit AC, Schmitz FJ, Jones ME, Acar J, Gupta R, Verhoef J. The SENTRY participants group. Antimicrobial resistance among community-acquired pneumonia isolates in Europe:First results from the SENTRY antimicrobial surveillance program 1997. Int J Infect Dis 1999;3:153-6.
[Table 1], [Table 2], [Table 3]