|Year : 2018 | Volume
| Issue : 1 | Page : 32-36
Antimicrobial susceptibility profiles of gram-negative bacteria causing infections collected across India during 2014–2016: Study for monitoring antimicrobial resistance trend report
Balaji Veeraraghavan1, Mark Ranjan Jesudason2, John Antony Jude Prakasah1, Shalini Anandan1, Rani Diana Sahni1, Agila Kumari Pragasam1, Yamuna Devi Bakthavatchalam1, Rajesh Joseph Selvakumar2, TN Dhole3, Camilla Rodrigues4, Indranil Roy5, Sangeetha Joshi6, Bhaskar Narayan Chaudhuri7, DS Chitnis8
1 Department of Clinical Microbiology, Christian Medical College, Vellore, Tamil Nadu, India
2 Department of General Surgery, Christian Medical College, Vellore, Tamil Nadu, India
3 Department of Microbiology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
4 Department of Microbiology, PD Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India
5 Department of Microbiology, Calcutta Medical Research Institute, Kolkata, West Bengal, India
6 Department of Microbiology, Manipal Hospital, Bengaluru, Karnataka, India
7 Department of Microbiology, Fortis Hospital, Anandapur, Kolkata, West Bengal, India
8 Department of Microbiology and Immunology, Choithram Hospital, Indore, Madhya Pradesh, India
|Date of Web Publication||2-May-2018|
Dr. Balaji Veeraraghavan
Department of Clinical Microbiology, Christian Medical College, Vellore - 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: The emergence of antibiotic resistance among bacterial pathogens in the hospital and community has increased the concern to the health-care providers due to the limited treatment options. Surveillance of antimicrobial resistance (AMR) in frequently isolated bacterial pathogens causing severe infections is of great importance. The data generated will be useful for the clinicians to decide empiric therapy on the local epidemiological resistance profile of the antimicrobial agents. This study aims to monitor the distribution of bacterial pathogen and their susceptibility pattern to the commonly used antimicrobial agents. Materials and Methods: This study includes Gram-negative bacilli collected from intra-abdominal, urinary tract and respiratory tract infections during 2014–2016. Isolates were collected from seven hospitals across India. All the study isolates were characterised up to species level, and minimum inhibitory concentration was determined for a wide range of antimicrobials included in the study panel. The test results were interpreted as per standard Clinical Laboratory Standards Institute guidelines. Results: A total of 2731 isolates of gram-negative bacteria were tested during study period. The most frequently isolated pathogens were 44% of Escherichia coli (n = 1205) followed by 25% of Klebsiella pneumoniae (n = 676) and 11% of Pseudomonas aeruginosa (n = 308). Among the antimicrobials tested, carbapenems were the most active, followed by amikacin and piperacillin/tazobactam. The rate of extended-spectrum beta-lactamase (ESBL)-positive isolates were ranged from 66%–77% in E. coli to 61%–72% in K. pneumoniae, respectively. Overall, colistin retains its activity in > 90% of the isolates tested and appear promising. Conclusion: Increasing rates of ESBL producers have been noted, which is alarming. Further, carbapenem resistance was also gradually increasing, which needs much attention. Overall, this study data show that carbapenems, amikacin and colistin continue to be the best agents available to treat drug-resistant infections. Thus continuous monitoring of susceptibility profile of the clinically important Gram-negative pathogens is of great importance to guide effective antimicrobial therapy.
Keywords: Antimicrobials, carbapenem, colistin, India, SMART, susceptibility
|How to cite this article:|
Veeraraghavan B, Jesudason MR, Prakasah JA, Anandan S, Sahni RD, Pragasam AK, Bakthavatchalam YD, Selvakumar RJ, Dhole T N, Rodrigues C, Roy I, Joshi S, Chaudhuri BN, Chitnis D S. Antimicrobial susceptibility profiles of gram-negative bacteria causing infections collected across India during 2014–2016: Study for monitoring antimicrobial resistance trend report. Indian J Med Microbiol 2018;36:32-6
|How to cite this URL:|
Veeraraghavan B, Jesudason MR, Prakasah JA, Anandan S, Sahni RD, Pragasam AK, Bakthavatchalam YD, Selvakumar RJ, Dhole T N, Rodrigues C, Roy I, Joshi S, Chaudhuri BN, Chitnis D S. Antimicrobial susceptibility profiles of gram-negative bacteria causing infections collected across India during 2014–2016: Study for monitoring antimicrobial resistance trend report. Indian J Med Microbiol [serial online] 2018 [cited 2019 May 25];36:32-6. Available from: http://www.ijmm.org/text.asp?2018/36/1/32/231676
| ~ Introduction|| |
Antimicrobial resistance (AMR) in Gram-negative bacteria (GNB) is persisting to be a significant cause of severe infections across the world, with increasing morbidity and mortality rates. Sepsis, respiratory tract infections (RTIs), intra-abdominal infections (IAI), skin and soft-tissue infections and urinary tract infections (UTI) are the most commonly encountered infections. The increasing occurrence of AMR for beta-lactam groups of antimicrobials is a major concern. It is mainly due to the presence of beta-lactamases that are carried on the mobile genetic elements, which accounts for the widespread event. Beta-lactamases are of diverse types, of which extended-spectrum beta-lactamases (ESBLs) and carbapenemases are reported to be rapidly disseminated.
Although AMR is rising globally, there is a significant variation in the resistance profile across different geographical locations. It is therefore important to monitor the rates of AMR in the clinically important pathogens at various regions across the world. This is imperative to track the trend in the changing resistance pattern over time, to guide proper therapeutic strategies to combat infections due to drug-resistant pathogens. Several large-scale surveillance studies are being conducted to monitor AMR across the globe. Studies have reported that the burden of AMR is high in Asian countries.
However, India being a participating site in the global AMR studies is negligible. Hence, there is a lack of information on the incidence rates and real burden of AMR in India. The study for monitoring AMR trend is a global surveillance program intended to monitor the efficacy of antimicrobials against GNB that cause IAIs, UTIs and RTIs. This report highlights the distribution of GNB isolated from IAIs, UTIs and RTIs; and their antimicrobial susceptibility profiles in India collected during 2014–2016.
| ~ Materials and Methods|| |
This study includes a total of 2731 clinical isolates of GNB isolated from IAIs, UTIs and RTIs. These were isolated during 2014–2016 across seven different hospitals from India. This includes Christian Medical College, Vellore; Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow; Hinduja Hospital, Mumbai; Calcutta Medical Research Institute, Kolkata; Manipal Hospital, Bangalore; Fortis Hospital, Kolkatta and Choithram Hospital, Indore. All the isolates were identified up to species level by standard biochemical tests. Minimum inhibitory concentration (MIC) was determined for antimicrobials using custom dehydrated Microscan broth dilution method. Susceptibility was interpreted according to breakpoints provided by CLSI guidelines for the respective years.,, Antimicrobials agents tested were as follows: cephalosporins (cefoxitin, ceftazidime, cefotaxime, cefepime and ceftriaxone); β-lactam/β-lactamase inhibitor (ampicillin/sulbactam and piperacillin/tazobactam); carbapenems (imipenem and ertapenem); monobactam (aztreonam); fluoroquinolones (ciprofloxacin and levofloxacin); aminoglycosides (amikacin) and polymyxins (colistin). Quality control (QC) was performed each day along with the isolates testing by CLSI recommended QC strains such as Escherichia coli ATCC 25922, E. coli ATCC 35218, Pseudomonas aeruginosa ATCC 27853 and Klebsiella pneumoniae ATCC 700603 (ESBL-positive control). Clinical isolates results were considered only if the QC strains MICs were within the acceptable ranges. ESBLs were classified based on the phenotype of ceftazidime being resistant, while susceptible to carbapenems (imipenem and meropenem). Carbapenem resistance (CR) was considered based on imipenem resistance alone for the study isolates.
| ~ Results|| |
Among the GNB isolates collected, E. coli(n = 1205) and Klebsiella spp (n = 676) are the most common, followed by P. aeruginosa (n = 308), other GNBs (n = 397) and Acinetobacter spp (n = 145). This was similar for intra-abdominal and UTI, while Klebsiella spp (n = 183) was more common in RTIs, followed by P. aeruginosa (n = 119), E. coli(n = 94), Acinetobacter baumannii (n = 71) and other GNBs (n = 85). No significant difference was noted with the pathogen distribution isolated across different regions. The distributions of GNBs collected during 2014–2016 are shown in [Figure 1].
|Figure 1: Distribution of Gram-negative bacteria isolated from intra-abdominal infections, urinary tract infections, respiratory tract infections during 2014–2016 collected across India|
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Among the antimicrobials tested, carbapenems were the most active, followed by amikacin and piperacillin/tazobactam. Among cephalosporins, the activity of cefoxitin was found superior than the other agents. Moderate activity was noted for fluoroquinolones and aztreonam [Table 1]. Notably, antimicrobial susceptibility profile revealed the increasing rates of ESBL producers among E. coli and Klebsiella spp were noted. About 64% of E. coli and 44% of Klebsiella spp were found to be ESBL producers. Subset analysis revealed that, in E. coli, ESBL rates were seen more in RTI (72%), followed by UTI (64%) and IAI (63%). Similarly, in Klebsiella spp, ESBL rates were higher in RTI (58%), followed by UTI (42%) and IAI (37%). Likewise, CR rates were higher in Klebsiella spp (39%) than E. coli(12%). In Klebsiella spp, CR-rates were high in UTI (41%), followed by IAI (39%) and RTI (38%). While in E. coli, CR-rates were high in RTI (19%), than UTI (14%) and IAI (11%). Overall, ESBL rates were high in E. coli, while CR was high in Klebsiella spp. Although number of tested isolates varied between IAI, UTI and RTI sources, E. coli isolated from RTIs showed high resistance rates, while Klebsiella spp isolated from UTIs were more resistant. This highlights the importance of understanding the differences in the resistance rates of organisms causing IAIs, UTI and RTIs.
|Table 1: Antimicrobial susceptibility profile Gram-negative bacteria collected during 2014-2016|
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In vitro antimicrobial susceptibility profile of extended-spectrum beta-lactamase producing organisms
[Table 2] summarises the antimicrobial susceptibility profile of E. coli and Klebsiella spp classified as ESBLs and non-ESBLs. For ESBL producers, imipenem and ertapenem were found to be the most active agent followed by piperacillin/tazobactam and amikacin. Imipenem susceptibility was 100%, while ertapenem showed 90%, 90% and 95% against ESBL E. coli isolated from IAI, UTI and RTI, respectively. While for ESBL Klebsiella spp, imipenem susceptibility was 100% and ertapenem showed 64%, 72% and 85% for isolates from IAI, UTI and RTI, respectively. Carbapenem activity was found superior for ESBL producing E. coli when compared to ESBL producing Klebsiella spp. Amikacin susceptibility ranged from 88%–95% to 70%–90% for ESBL producing E. coli and Klebsiella spp, respectively. Overall, susceptibility rates were found to be less for Klebsiella spp. Notably, cefoxitin susceptibility ranged from 26%–58% to 43%–53%, while piperacillin/tazobactam showed 60%–62% and 44%–54% for ESBL producing E. coli and Klebsiella spp, respectively. Fluoroquinolone activity was found to be the least being <20% for ESBL producing E. coli and 40%–63% for ESBL producing Klebsiella spp.
|Table 2: Antimicrobial susceptibility profile of extended spectrum beta-lactamases versus non-extended spectrum beta-lactamases Escherichia coli and Klebsiella spp. collected during 2014-2016|
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In vitro antimicrobial susceptibility profile of carbapenem-resistant organisms
[Table 3] summarises the antimicrobial susceptibility profile of E. coli and Klebsiella spp classified as carbapenem susceptible (CS) and carbapenem-resistant. CR was seen more in Klebsiella spp (39%) than E. coli(12%). For CR-E. coli and CR-Klebsiella spp, amikacin was the only agent which showed moderate activity. This ranged from 22% to 46% for CR-E. coli and 17% to 25% for CR-Klebsiella spp. The highest activity of amikacin was about 46% for CR-E. coli and 25% for CR-Klebsiella spp isolated from UTIs. While susceptibility to other antimicrobials were <15% for CR-E. coli and CR-Klebsiella spp. For CS E. coli and Klebsiella spp, amikacin and piperacillin/tazobactam were the most active agents. Among cephalosporins, cefoxitin was found to have the highest susceptibility than other agents. Fluoroquinolones and aztreonam activity was <50% and found to be the least active. For P. aeruginosa and A. baumannii, amikacin was the only agent which was active for about 55% and 30%, respectively (data not shown). Colistin was the most active agent found to have >95% susceptibility for P. aeruginosa and A. baumannii, respectively.
|Table 3: Antimicrobial susceptibility profile of carbapenem susceptible versus carbapenem-resistant Escherichia coli and Klebsiella spp. collected during 2014-2016|
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| ~ Discussion|| |
Country-based incidence and antimicrobial susceptibility profile of clinical pathogens are essential. Infections due to Gram-negative organisms are commonly encountered in the clinical practice. Although many GNB causes severe infections, E. coli, Klebsiella spp, P. aeruginosa and A. baumannii are the most commonly encountered pathogens. Thus, the increasing AMR in these pathogens posing a global threat needs to be monitored. In particular, ESBL rates are alarmingly increasing in E. coli and Klebsiella spp, which accounts for about 70%. This is particularly high in India, wherein our study report concurs with the previous findings with high ESBL rates in India, China, Thailand and Vietnam., In India, blaCTX-M-mediated ESBLs are more common, followed by blaTEM and blaSHV (data not shown). As susceptibility rates to cephalosporins are severely decreasing, cephalosporins should not be a preferable choice for empirical therapy. While carbapenems have been considered as an alternative for empiric therapy, where the incidences of ESBLs are high.
In this study, carbapenem agents including imipenem and ertapenem exhibited moderate activity. However, there has been an increase in the CR over the past few years. In India, CR E. coli and Klebsiella spp are mainly due to the presence of metallo-beta-lactamases-blaNDM and Class D carbapenemases-blaOXA-48 like. While blaVIM in P. aeruginosa and blaOXA-23,24,58 like in A. baumannii are the predominant CR noted. Colistin remains as the last resort of drug for treating severe infections due to carbapenem-resistant organisms. Molecular characterisation of AMR in the resistance isolates warrants the strategies to be implemented to control the further spread of AMR determinants. However, the older drug colistin remains as the last resort for treating infections due to CR-organisms. Further, the recently Food and Drug Administration approved agents such as ceftazidime/avibactam and ceftolozane/tazobactam could be better alternatives. These agents could serve as a better alternative depending on the pathogen and the mechanism of resistance.
This study demonstrates the high ESBL frequencies observed in India, with ESBL being the dominant phenotype, alarmingly so high in India, which concurs with the previous studies.[10-14] In addition, resistance was observed high to the majority of the antimicrobials tested, with the exception of the carbapenems and amikacin. It is imperative to point out that, despite the high and increasing ESBL rates within Asia, and in particular in India, most ESBL-producing isolates remain susceptible to these important antibiotic classes. Further, in-depth studies highly warrant tracking the ever-increasing AMR to guide drug of choice for effective empirical therapy.
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Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Vasoo S, Barreto JN, Tosh PK. Emerging issues in gram-negative bacterial resistance: An update for the practicing clinician. Mayo Clin Proc 2015;90:395-403.
Versalovic J, Carroll KC, Funke G, Jorgensen JH, Landry ML, Warnock DW, editors. Manual of Clinical Microbiology. 10th
ed. Washington, D.C: American Society for Microbiology; 2011.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty Fourth Informational Supplement. CLSI Document M100-S24. Wayne, PA: Clinical and Laboratory Standards Institute; 2014.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty Fifth Informational Supplement. CLSI Document M100-S25. Wayne, PA: Clinical and Laboratory Standards Institute; 2015.
Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing; Twenty Sixth Informational Supplement. CLSI Document M100-S26. Wayne, PA: Clinical and Laboratory Standards Institute; 2016.
Hawser SP, Bouchillon SK, Hoban DJ, Badal RE, Hsueh PR, Paterson DL, et al.
Emergence of high levels of extended-spectrum-beta-lactamase-producing gram-negative bacilli in the Asia-pacific region: Data from the study for monitoring antimicrobial resistance trends (SMART) program, 2007. Antimicrob Agents Chemother 2009;53:3280-4.
Yang Q, Zhang H, Wang Y, Xu Y, Chen M, Badal RE, et al.
A 10 year surveillance for antimicrobial susceptibility of Escherichia coli
and Klebsiella pneumoniae
in community- and hospital-associated intra-abdominal infections in China. J Med Microbiol 2013;62:1343-9.
Castanheira M, Deshpande LM, Mathai D, Bell JM, Jones RN, Mendes RE, et al.
Early dissemination of NDM-1- and OXA-181-producing Enterobacteriaceae
in Indian hospitals: Report from the SENTRY antimicrobial surveillance program, 2006-2007. Antimicrob Agents Chemother 2011;55:1274-8.
Pragasam AK, Vijayakumar S, Bakthavatchalam YD, Kapil A, Das BK, Ray P, et al.
Molecular characterisation of antimicrobial resistance in Pseudomonas aeruginosa
and Acinetobacter baumannii
during 2014 and 2015 collected across India. Indian J Med Microbiol 2016;34:433-41.
] [Full text]
Jean SS, Coombs G, Ling T, Balaji V, Rodrigues C, Mikamo H, et al.
Epidemiology and antimicrobial susceptibility profiles of pathogens causing urinary tract infections in the Asia-Pacific region: Results from the Study for Monitoring Antimicrobial Resistance Trends (SMART), 2010–2013. International Journal of Antimicrobial Agents 2016;47:328-34.
Chaudhuri BN, Rodrigues C, Balaji V, Iyer R, Sekar U, Wattal C, et al.
Incidence of ESBL producers amongst Gram-negative bacilli isolated from intra-abdominal infections across India (based on SMART study, 2007 data). JAPI 2011;59:1-6.
Hawser SP, Badal RE, Bouchillon SK, Hoban DJ. SMART India Working Group. Antibiotic susceptibility of intra-abdominal infection isolates from Indian hospitals during 2008. Journal of Medical Microbiology 2010;59:1050-4.
Hsueh PR, Badal RE, Hawser SP, Hoban DJ, Bouchillon SK, Ni Y, et al.
Epidemiology and antimicrobial susceptibility profiles of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia–Pacific region: 2008 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). International Journal of Antimicrobial Agents 2010;36:408-14.
Chang YT, Coombs G, Ling T, Balaji V, Rodrigues C, Mikamo H, et al.
Epidemiology and trends in the antibiotic susceptibilities of Gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacific region, 2010–2013. International Journal of Antimicrobial Agents 2017;49:734-9.
[Table 1], [Table 2], [Table 3]