|Year : 2023 | Volume
| Issue : 1 | Page : 35-43
Tracking Annual Antimicrobial Resistance at a Tertiary Care Hospital amidst Raging COVID-19 Pandemic
Sonal Saxena, Prabhav Aggarwal
Department of Microbiology, Maulana Azad Medical College, New Delhi, India
|Date of Submission||08-Aug-2022|
|Date of Acceptance||26-Dec-2022|
|Date of Web Publication||28-Apr-2023|
Department of Microbiology, Maulana Azad Medical College, BSZ Marg, New Delhi - 110002
Source of Support: None, Conflict of Interest: None
Background: Timely preparation and presentation of the annual cumulative antibiogram play an important role in the dissemination of an updated susceptibility pattern to clinicians and thus aid in the appropriate choice of antimicrobials for empirical therapy while minimizing adverse effects and resistance. The study aimed to present and analyze the annual AMR data that may be helpful in designing antibiotic policy. Methods: All clinical specimens routinely submitted to the Department of Microbiology from January to December 2021 for bacteriological culture and antimicrobial susceptibility testing (AST) were included. AST was performed for pathogenic isolates by disc diffusion/agar dilution/broth microdilution methods/VITEK® 2 compact system. All data were entered and analyzed using WHONET 2020 software. Results: A total of 46,629 routine specimens were processed, yielding 5792 non-repeat bacterial isolates. Relatively fewer specimens were received during the first few months when the hospital catered exclusively to COVID-19 patients. The most common bacterial isolates were Escherichia coli (30%), Staphylococcus aureus (21%), Klebsiella sp. (18%), Pseudomonas sp. (10%), Acinetobacter sp. (8%) and Enterococcus sp. (5%). Analysis showed low susceptibility to 3rd generation cephalosporins, fluroquinolones, and cotrimoxazole among Gram negative bacteria. Less than 50% Acinetobacter sp. were carbapenem susceptible. We report high rate of methicillin resistance in S. aureus (74%). Overall susceptibility was much lower in specimens from ICU followed by in-patients and out-patients. Conclusion: Antimicrobial resistance is rapidly assuming the proportions of a pandemic, with several authors calling it “invisible” pandemic. As is evident from the present study, low susceptibilities to all but a few last-resort drugs are leaving few choices for treatment. This mandates effective preparation, distribution, and presentation of annual antibiograms, which will help in formulating hospital antibiotic policy.
Keywords: Antibiogram, antimicrobial resistance, priority pathogens, surveillance
|How to cite this article:|
Saxena S, Aggarwal P. Tracking Annual Antimicrobial Resistance at a Tertiary Care Hospital amidst Raging COVID-19 Pandemic. MAMC J Med Sci 2023;9:35-43
|How to cite this URL:|
Saxena S, Aggarwal P. Tracking Annual Antimicrobial Resistance at a Tertiary Care Hospital amidst Raging COVID-19 Pandemic. MAMC J Med Sci [serial online] 2023 [cited 2023 Jun 6];9:35-43. Available from: https://www.mamcjms.in/text.asp?2023/9/1/35/375334
| Introduction/ Background|| |
Antimicrobial resistance (AMR) has emerged as a major public health problem across the world. While increasing antimicrobial resistance poses a global threat, situation is particularly grim in the Indian context. With new antimicrobial drug discovery slowing down and bacteria rapidly becoming resistant to the available drugs, our options are becoming increasingly limited. In 2013, Margaret Chan, Director-General of the WHO, warned about the post-antibiotic era that we are fast approaching and said, “Things as common as a strep throat or a child’s scratched knee could once again kill.” Yet, as per the report by The Pew Charitable Trusts, as of December 2020, there were only 43 new antibiotics in development; of these, only 13 are in phase III clinical trials, and only about half of these might eventually be approved.
In view of the above-stated developments, antimicrobial stewardship (AMS) is being looked at as an absolute necessity. WHO has defined AMS as a coherent set of actions that promote the responsible use of antimicrobials. This definition can be applied to actions at the individual, national, and global levels, and across human health, animal health, and the environment. Good AMS practices begin with good data collection and presentation. The most accepted method of data presentation for AMR at the local hospital level is the annual cumulative antibiogram. Clinical Laboratory Standards Institute has defined a cumulative antibiogram as the report generated by analysis of results on isolates from a particular institution(s) in a defined period of time that reflects the percentage of first isolates (per patient) of a given species that is susceptible to each of the antimicrobial agents routinely tested.
Clinical microbiologists in any clinical or hospital setting have the responsibility for accurate bacterial culture and antimicrobial susceptibility testing (AST). Besides daily specimen-wise AST reporting, the cumulative data thus generated must be analysed and presented to the clinicians in a timely and easy to understand manner. Clinical microbiologists thus have a critical role to play in the dissemination of information and educating the clinical departments about the prevalent resistance and susceptibility patterns in various local sections of the hospital (OPD/IPD/ICU), thus enabling the formulation of customised hospital antibiotic policy. With this aim, this study was designed to present and analyse the annual AMR data that will be helpful in designing antibiotic policy, not only at the local hospital or city level, but also at national level. Further, this presentation and analysis may encourage and facilitate other clinical settings to prepare and disseminate their own antibiograms in their institutes.
| Materials and Methods|| |
The study was conducted at the Department of Microbiology, of a premier medical college and associated 2000-bedded tertiary care hospital in India. All clinical specimens routinely submitted to the Department of Microbiology from January to December 2021 for bacteriological culture and antimicrobial susceptibility testing were considered for the study. No clinical specimen was collected specially and exclusively for the purpose of the study.
Depending on the clinical sample, the specimens were inoculated on suitable bacteriological culture media (Blood agar, Chocolate agar, MacConkey’s agar, Cysteine Lysine Electrolyte deficient agar, Bile salt agar, Xylose Lysine Deoxycholate agar, Cooked Meat broth) before and after enrichment. Only suspected pathogenic bacterial isolates growing on the culture media were further processed. Commensals and contaminating organisms were not processed further. Gram negative isolates in mid-stream urine were processed if colony counts were >105 CFU/mL. Mixtures of three or more types of bacterial growth were considered as contaminants and a repeat sample was requested. Bacterial species were identified using conventional biochemical methods and/or automated VITEK® 2 compact.
Antimicrobial susceptibility testing was performed for pathogenic isolates by disc diffusion/ agar dilution/ broth microdilution methods and/ or VITEK® 2 compact system and interpreted as per CLSI guidelines. The antibiotic panel tested for each isolate was decided based on the intrinsic susceptibility of the organism, the clinical site of infection, the availability of the drug in hospital formulary and Standard operating Procedures, National AMR Surveillance Network, National Centre for Disease Control (NCDC). NCDC has identified the following priority bacterial pathogens from blood, pus + other sterile body fluids (OSBF) and urine specimen: Escherichia coli, Klebsiella sp., Pseudomonas sp., Acinetobacter sp., S. aureus (except from urine), Enterococcus sp. and Salmonella sp. (from blood and stool samples); hence the antibiogram will focus on these priority pathogens.
| Data Analysis and Statistics|| |
All the data thus generated were entered in real-time in the WHONET 2020 software by trained data entry operator/ technicians/ resident doctors under the supervision of a senior clinical microbiologist. The data were analysed using the same software, that is, WHONET 2020 and presented as percentages and proportions. Data for antimicrobial susceptibility testing were presented as a percentage of bacterial isolates tested that were susceptible to the antimicrobial agent tested by routine in vitro methods.
The present analysis has taken care to follow following recommendations for the preparation of antibiogram:
- Only the first isolate of a given species per patient irrespective of the specimen site has been included.
- Only those groups or sub-subgroups of each bacterial species have been included for which at least 30 isolates have been tested. For others, data have been presented with a comment that few (<30) isolates have been tested.
- Only the isolates obtained from specimens submitted for routine clinical diagnostic testing have been included.
- Specimens tested for environmental surveillance or infection control purposes and quality control have not been included.
- Colonisers/commensals have also been excluded.
- The cumulative antibiogram presents only the percentage susceptible and not those which are intermediate susceptible. However, for colistin, we have included intermediate susceptible category, since CLSI has withdrawn the susceptible category citing adverse effects and limited clinical efficacy.
- The antibiogram has been stratified according to patient location (outpatient, inpatient and ICU) and also according to the specimen type.
- In case both Minimum Inhibitory Concentration (MIC from Vitek®/ agar dilution/ broth microdilution) and disc diffusion results were available for an isolate, MICs were given preference.
| Results|| |
Over a period of 1 year (January–December 2021), a total of 46,629 specimens were received in the Department of Microbiology for bacteriological culture and antimicrobial susceptibility testing. These included 22,011 (47.2%) urine specimens, 7238 (15.5%) blood culture specimens, 9741 (20.9%) pus specimens, 4255 (9.1%) other sterile body fluids, 911 (2.0%) stool culture specimens and 2473 (5.3%) other specimen including respiratory specimen. Majority of samples were from in-patients (55.7%), followed by OPD (37.9%) and ICU (6.3%). 51%, 44% and 5% of the urine samples were from OPD, IPD and ICU respectively. Blood culture, pus and other sterile body fluids were largely from in-patients (84%, 54% and 76%, respectively).
A total of 5792 non-repeat bacterial strains from various clinical specimens fulfilling inclusion and exclusion criteria were included in the study [Figure 1]. Most frequently isolated bacterial species were E. coli (30%), S. aureus (21%), Klebsiella sp. (18%), Pseudomonas sp. (10%), Acinetobacter sp. (8%) and Enterococcus sp. (5%) followed by Citrobacter sp. (4%), Proteus sp. (2%) and other bacterial species. Number of bacterial isolates cultured from various specimens is detailed in [Table 1]. Highest isolation from blood culture, Pus + other sterile body fluids and urine were of S. aureus (336 isolates from blood and 760 isolates from pus + OSBF) and E. coli (832 isolates from urine), respectively. All Shigella sp. and Vibrio cholerae were cultured from stool specimens [Table 2].
|Figure 1 Bacterial species isolated from all clinical specimen during year 2021 (n = 5792).|
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|Table 1 Number of bacterial isolates cultured from various clinical specimen (n = 5792)|
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|Table 2 Overall percent susceptibility (S%) of common bacterial isolates to antimicrobial agent tested.|
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The month-wise distribution of common priority bacterial isolates is detailed in [Table 1]. Corresponding with the high number of COVID-19 cases in Delhi towards the end of the year 2020 and the beginning of the year 2021 and then again during March to June 2021, the hospital was partly or completely declared an exclusive COVID-19 hospital. Hence, the hospital saw relatively few non-COVID-19 patients during these months with very few specimens being received for routine bacteriological culture [Figure 2]. As a result, as presented in [Table 1], the number of bacterial isolates was relatively few during the initial 6 months of the year. More than 60% of the isolates of each of the bacterial isolates were from in-patients, followed by out-patient department and intensive care units [Figure 3].
The overall susceptibility pattern of the commonly isolated bacterial species isolated over a period of 1 year is depicted in [Table 3]. For E. coli, susceptibility percentage was particularly low for ampicillin (13%), ceftriaxone/ cefotaxime (20%), cefepime (22%), ciprofloxacin (26%), cotrimoxazole (37%), while carbapenems (70–77%), amikacin (73%), minocycline (73%) retained some activity. Klebsiella sp. generally showed a similar pattern, albeit with slightly lower susceptibility to all drugs in comparison to E. coli. For Acinetobacter sp., less than 50% of the strains were susceptible to most antibiotics, including carbapenems; except for colistin (98%) and minocycline (85%). In comparison, Pseudomonas sp. showed higher susceptibility to all antibiotics.
|Table 3 Specimen wise percent susceptibility (S%) of Escherichia coli and Klebsiella sp. isolates|
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Very few isolates of Shigella sp. (08 isolates), Salmonella sp. (07 isolates) and Vibrio cholerae (04 isolates) were identified during 2021. As a result, the antibiogram for these isolates may not depict true susceptibility profiles. All Salmonella sp. and Vibrio cholerae were susceptible to 3rd generation cephalosporins, 02 isolates (out of 8) of Shigella sp. showed resistance to 3rd generation cephalosporins.
Among Gram positive organisms, 95% of the strains of Enterococcus sp. and >99% of the Staphylococci were Vancomycin susceptible. Similarly, Linezolid for both Staphylococci and Enterococci; and Teicoplanin for Enterococci showed good susceptibility. 74% of the isolates of S. aureus were Methicillin Resistant, as determined by resistance to cefoxitin.
In general, it was found that the isolates from the ICU showed lower susceptibility than those from the admitted patients; who in turn were less susceptible than the isolates from out-patients. Differences in location-wise susceptibility patterns for the six most frequently isolated bacterial pathogens are depicted in [Figures 4]a–f. For the Gram negative bacteria, the difference is particularly notable for the beta lactam group of drugs, such as piperacillin-tazobactam, cephalosporins, imipenem, meropenem and also for ciprofloxacin and aminoglycosides. Specimen-wise comparison of the susceptibility pattern of the priority pathogens is depicted in [Table 3],[Table 4],[Table 5]. The patterns were consistent across all specimens, with urine isolates showing slightly better susceptibility as compared to blood and pus + OFBF.
|Figure 4 (a–f) Location wise susceptibility pattern (S%) of common priority pathogens. (a) Escherichia coli, (b) Klebsiella sp., (c) Pseudomonas sp., (d) Acinetobacter sp., (e) Staphylococcus aureus, (f) Enterococcus sp. Note: Enterococci isolated form ICU were <30, antibiogram may not depict true pattern. Abbreviations: AMP, Ampicillin; AMC, Amoxycillin/Clavulanate; AMK, Amikacin; ATM, Aztreonam; CAZ, Ceftazidime; CIP, Ciprofloxacin; CLI, Clindamycin; COL, Colistin; CTX, Cefotaxime; CRO, Ceftriaxone; DOX, Doxycycline; ERY, Erythromycin; FEP, Cefepime; FOX, Cefoxitin; IMP, Imipenem; LNZ, Linezolid; GEN, Gentamicin; MEM, Meropenem; MNO, Minocycline; NIT, Nitrofurantoin (urine isolates only); NET, Netilmicin; SXT, Trimethoprim/Sulfamethoxazole; TZP, Piperacillin/Tazobactam; TEC, Teicoplanin; VAN, Vancomycin.|
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|Table 4 Specimen-wise percent susceptibility (S%) of Pseudomonas sp. and Acinetobacter sp. isolates|
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|Table 5 Specimen-wise percent susceptibility (S%) of Staphylococcus aureus and Enterococcus sp.|
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| Discussion|| |
On the basis of a predictive statistical models, a group of Antimicrobial Resistance Collaborators estimated 4.95 million deaths associated with bacterial AMR in 2019. They also estimated that the six leading pathogens for deaths associated with resistance (E. coli, followed by S. aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929,000 deaths attributable to AMR. Another study projected that by 2050, the deaths due to AMR may exceed deaths due to cancers.
The COVID-19 pandemic gained immediate attention with its speed of spread and the devastation it caused. AMR, on the other hand, remains invisible and unrecognised and is reflected only in prolonged bacterial infections that extend hospital stays and cause deaths. Worldwide, the authors are now realising its full potential and AMR has been termed an “overlooked” or “invisible” pandemic., Further, it remains to be seen the effect of COVID-19 pandemic on AMR. While improved hand hygiene, decreased international travel, and decreased elective hospital procedures may reduce AMR in near-term, the opposite effects may be seen since antibiotics are being used widely. During the initial months when our hospital was exclusively looking after patients with COVID-19, bacteriological sections of the Department received few samples. This may have influenced the antibiogram.
A cumulative hospital antibiogram represents a summary of the antimicrobial susceptibilities of local bacterial isolates submitted to the hospital’s clinical microbiology laboratory over a defined period. Antibiograms can be used by clinicians to assess local susceptibility rates, aid in selecting empiric antibiotic therapy and monitor resistance trends over time within an institution. They can also be used to compare susceptibility rates and track resistance trends over time across institutes, cities, states and countries. Local hospital level antibiograms can also aid in fine-tuning the hospital antibiotic policies based on the clinical speciality, patient location (OPD/IPD/ICU), clinical site of infection, patient load, and special procedures being performed.
The preparation of a quality hospital antibiogram is the first step towards building national-level data for AMR surveillance. A hospital antibiogram may be presented in either of the two ways: susceptibility percentage (S%) or resistance percentage (R%). Since the clinical decision for antimicrobial use is based on susceptibility rather than resistance, we have chosen percent susceptible (S%), as has also been recommended by CLSI. However, some groups have chosen to present data as a percent of resistance (R%) since it may help in creating greater awareness and administrative action.,
In the present study, we discuss the susceptibility profile of clinical bacterial isolates, with detailed location-wise and specimen-wise discussion of top six priority bacterial species with higher numbers of isolation. The National Antimicrobial Resistance Surveillance Network initiated by the Ministry of Health and Family Welfare with National Centre for Disease Control (NCDC) as the national focal point, have also mandated these six organisms and typhoidal Salmonellae as the priority bacterial pathogens. Additionally, globally these organisms are estimated to be the leading cause of deaths attributable to AMR.
In our study, from a total of 46,629 specimens cultured, 5792 non-repeat pathogenic bacterial strains were isolated, giving a yield of 12.4%. Our antibiogram closely follows the national data. Fourth annual report of the National AMR Surveillance Network (NARS-Net India) published by National Centre for Disease Control (NCDC) has been published in 2021. It presents data received from 29 sentinel surveillance laboratories in 24 states/UTs. Similarly, Indian Council of Medical Research (ICMR) has published 4th Annual Report of Antimicrobial Resistance Research & Surveillance Network (AMRSN) in 2020. Top six organism were similar in ICMR, NCDC and our data, though order was slightly different. ICMR reported E. coli (25.1%), K. pneumoniae (18%), P. aeruginosa (12%), A. baumanni (12%), Staphylococcus aureus (9.6%) and Enterococci sp. (7.3%) as most common bacterial agents, in descending order; while NCDC reported E. coli as most frequent, followed by Klebsiella sp., S. aureus, Pseudomonas sp. and Enterococcus sp. and Acinetobacter sp.,
On the global scale, the World Health Organization − Global Antimicrobial Resistance and Use Surveillance System (WHO-GLASS) Report 2021 has shown that antimicrobial resistance is a greater problem in low- and middle income countries (LMICs), including India, as compared to high-income countries (HICs). For instance, an important difference in rates of E. coli resistance to 3rd generation cephalosporins was reported between LMICs (58.3% resistance; IQR 39.8–70.2) and HICs (17.53% resistance; IQR 11.3–25.2) in bloodstream infection isolates. In our study, less than one-fourth of Gram negative bacterial isolates were susceptible to 3rd generation cephalosporins. Low susceptibility in Gram negative bacterial leave very few choices for empirical treatment, with carbapenems being frequently prescribed in admitted patients on empirical basis. Susceptibility to colistin was high (99%), however, clinical trials have demonstrated limited clinical efficacy. As a result of less than satisfactory clinical outcomes and adverse effects, CLSI has removed the “susceptible” category for colistin and introduced only “intermediate susceptible” low strains with MIC ≤2 mg/L. However, EUCAST has maintained the susceptible breakpoint of ≤2 mg/L.,
Similarly, low susceptibility was seen among the Gram positive isolates to erythromycin, clindamycin, cotrimoxazole, ciprofloxacin. Only 26% of the S. aureus were cefoxitin susceptible, which is used as a surrogate to test for methicillin susceptibility. Hence, we have reported an overall 74% MRSA (Methicillin resistant S. aureus). In blood and pus + OSBF samples, MRSA was 68% and 78%, respectively. WHO-GLASS 2021 report, recorded median rates of 33.3% (IQR 19.5–55.6) in LMICs and 15% (IQR 6.8–36) in HICs of MRSA in blood stream infections. NCDC and ICMR have reported 56% and 41.4%, respectively.,
In our antibiogram, the susceptibility to high level gentamicin (HLG) in Enterococci was only 41%. ICMR has reported 27–60% susceptibility depending on species and specimen type, with Enterococcus faecalis being more resistant than Enterococcus faecium. Resistance to HLG indicates that synergy is not likely between aminoglycosides and susceptible cell wall active agents (e.g., ampicillin, penicillin and vancomycin) and hence, they should not be used in combination therapy. For both Staphylococci and Enterococci, Vancomycin and Linezolid remained highly effective, as in other studies. However, as other antibiotics are losing susceptibility, these higher agents are at risk of being overused and misused, and thus, we may see an increasing trend of resistance to these agents as well.
Location-wise analysis of susceptibility patterns of priority pathogens reveals that isolates from the ICU have the lowest susceptibility, followed by inpatients and then outpatients. This is on expected lines as in comparison to out-patient with limited hospital exposure, admitted patients in ICU and wards are more likely to have been exposed to multiple antibiotics and multi-drug resistant organisms. Specimen-wise analysis showed similar patterns across different specimen types, with some differences. In general, urine isolates were the most susceptible, followed by pus+ OSBF and blood cultures. The difference can be explained by the fact that 51% of urine samples were from OPD, while blood and pus + OSBF were largely from in-patients. Similar specimen-wise differences have also been reported by NCDC in their annual report.
| Conclusions|| |
The antibiogram clearly highlights the grim situation that the medical field is facing, and the data suggest that it is only going to worsen overtime if actions are not taken in the right direction. This mandates effective preparation, distribution, and presentation of annual antibiograms, which will help in formulating hospital antibiotic policies and monitor the trend of bacterial resistance over the years. Adhering to principles of antimicrobial stewardship is the need of the hour, as it aims to optimize antibiotics use, promote behaviour change in antibiotic prescribing and dispensing practices, reduce further emergence, selection, and spread of AMR, limit the adverse economic impact of AMR, and build health-care professionals best-practices regarding the rational use of antibiotics.
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Conflicts of interest
The authors report no conflicts of interest.
| References|| |
Kåhrström C. Entering a post-antibiotic era? Nat Rev Microbiol 2013;11:146.
Clinical and Laboratory Standards Institute. Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data; Approved Guideline—Fifth Edition. CLSI document M39. Wayne, PA: Clinical and Laboratory Standards Institute; 2022.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing. 31st ed. CLSI supplement M100. Clinical and Laboratory Standards Institute; 2021.
Murray CJL, Ikuta KS, Sharara F et al.
Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 2022;399:629–55.
Laxminarayana R. The overlooked pandemic of antimicrobial resistance. Lancet 2022;399:606–7.
United Nations. UN News. Global Perspective Human Stories. UN Health Agency Steps Up Fight Against ‘Invisible Pandemic’ Of Antimicrobial Resistance; 2019. Available at: https://news.un.org/en/story/2019/06/1040741
. (Accessed June 10, 2022).
Satlin MJ, Lewis JS, Weinstein MP et al.
Clinical and laboratory standards institute and European Committee on Antimicrobial susceptibility testing position statements on polymyxin b and colistin clinical breakpoints. Clin Infect Dis 2020;71:e523–9.
The European Committee on Antimicrobial Susceptibility Testing. Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 12.0; 2022. Available at: http://www.eucast.org
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]