|Year : 2019 | Volume
| Issue : 2 | Page : 87-96
Antimicrobial susceptibility profile & resistance mechanisms of Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens from India
Balaji Veeraraghavan1, Kamini Walia2
1 Department of Clinical Microbiology, Christian Medical College, Vellore, India
2 Division of Epidemiology & Communicable Diseases, Indian Council of Medical Research, New Delhi, India
|Date of Submission||30-Jan-2018|
|Date of Web Publication||3-Jun-2019|
Dr Balaji Veeraraghavan
Department of Clinical Microbiology, Christian Medical College, Vellore 632 004, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Antimicrobial resistance is a major concern globally. Infections due to drug-resistant pathogens are becoming difficult and a challenge to treat. As treatment choices are limited due to the high-drug resistance rates, there is an increase in the health care cost, duration of hospital stay, morbidity and mortality rates. Understanding the true burden of antimicrobial resistance for a geographical location is important to guide effective empirical therapy. To have a national data, it is imperative to have a systemic data capturing across the country through surveillance studies. Very few surveillance studies have been conducted in India to generate national data on antimicrobial resistance. This review aims to report the cumulative antibiogram and the resistance mechanisms of Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens from India.
Keywords: Antimicrobial - Global Antimicrobial Resistance Surveillance System priority pathogens - GLASS - India resistance - susceptibility
|How to cite this article:|
Veeraraghavan B, Walia K. Antimicrobial susceptibility profile & resistance mechanisms of Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens from India. Indian J Med Res 2019;149:87-96
|How to cite this URL:|
Veeraraghavan B, Walia K. Antimicrobial susceptibility profile & resistance mechanisms of Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens from India. Indian J Med Res [serial online] 2019 [cited 2020 May 28];149:87-96. Available from: http://www.ijmr.org.in/text.asp?2019/149/2/87/259593
| Introduction|| |
Infectious disease burden and antimicrobial resistance are major public health threat globally and particularly in India. While resistance is more significant in Gram-negative pathogens than Gram-positive organisms, the precise extent of this problem is not clear. In India, there is no systemic or national surveillance programme. Only a few multicentre studies and reports from individual units or hospitals have reported on antimicrobial resistance. In light of this, the Indian Council of Medical Research (ICMR), New Delhi, has established an antimicrobial resistance surveillance network (ICMR-AMRSN) in 2014 collaborating tertiary care hospitals across India (http://iamrsn.icmr.org.in/index.php/amrsn/amrsn-network).
This enlightens the systemic data capturing system with reliable data generated with quality control in place. In this article, the cumulative antibiogram and the molecular mechanisms of antimicrobial resistance for Global Antimicrobial Resistance Surveillance System (GLASS) priority pathogens (Gram-positive and Gram-negative organisms) are discussed. GLASS priority pathogens include Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, Streptococcus pneumoniae, Salmonella spp. and Shigella spp. (http://www.who.int/glass/en/). Indian studies from the published literature (2011-2017) and data from the AMRSN network have been analyzed.
| Gram-Positive Organisms|| |
In general, for Staphylococcus aureus, susceptibility profile of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) is reported separately. Overall, the median MRSA proportion is 40 per cent, with an interquartile range 34-44 per cent [interquartile range (IQR): 37-41]. Currently, susceptibility profile among MSSA is as follows; gentamicin (68-96%; IQR: 83-92), erythromycin (43-74%; IQR: 56-60), clindamycin (71-90%; IQR: 80-85), co-trimoxazole (54-79%; IQR: 63-78) and ciprofloxacin (31-53%; IQR: 32.5-44.5). While for MRSA, poor susceptibility to gentamicin (28-44%; IQR: 30-43), erythromycin (9-69%; IQR: 13-51), clindamycin (35-71%; IQR: 44-63), co-trimoxazole (27-66%; IQR: 35-62) and ciprofloxacin (8-21%; IQR: 5-21) is seen ,,,. Almost 100 per cent of methicillin resistance in S. aureus is recognized with mec A gene, but mec C-mediated methicillin resistance has not yet been reported from humans in India .
There are limited data on the distribution of aminoglycoside-modifying enzymes (AMEs) encoding for aminoglycoside resistance in S. aureus. Perumal et al have reported the bi-functional enzyme aac (6′)Ieaph (2'') (55.4%) as the predominant AME followed by aph (3') IIIa (32.3%) and ant (4') Ia gene (9%). The incidence of inducible (iMLSB) and constitutive (cMLSB) clindamycin resistance was higher in MRSA (iMLSB; 19-28%, cMLSB; 17-41%) than MSSA (iMLSB; 6-10 per cent, cMLSB; 5-10%),,,,,,. Inducible clindamycin resistance is conferred through erm A (20%) and erm C (52%) genes .
Although 100 per cent susceptibility to vancomycin is seen for S. aureus, yet only limited information on vancomycin-intermediate S. aureus (VISA) and heteroresistant VISA (hVISA) are available. Studies reported 5.8-6.9 per cent hVISA prevalence and most of the isolates showed vancomycin minimum inhibitory concentration (MIC) of ≥1.5 μg/ml ,. Our group has reported hVISA (n=17) harbouring multiple chromosomal mutations in teicoplanin-resistant operon (tca RAB), vancomycin resistance associated (vra SR), glycopeptide resistance-associated (graSR), cell wall regulating phosphorylase (walKR) two component systems (TCS) and rpo B gene ,. In addition, 10 VISA isolates with the vancomycin MIC of 4 μg/ml by microbroth dilution method was reported . A systemic review and meta-analysis on epidemiology of hVISA and VISA worldwide has reported the pooled prevalence of six and three per cent, respectively .
As of May 2015, there have been 14 vancomycin-resistant S. aureus (VRSA) cases reported in the USA since 2002. Thus, the identification of a VRSA is rare and should be treated as a highly unusual event . Glycopeptide non-susceptible coagulase-negative staphylococci (CoNS) have also been reported . From India, two VRSA carrying van A gene was documented with the MIC of ≥32 μg/ml . In addition, three isolates of linezolid-resistant S. aureus were reported (LRSA) with the MIC of >8 μg/ml; one isolate had the mutation of G2576U in 23S rRNA and the other two isolates were documented with plasmid linezolid resistant cfr gene ,. Two reports of daptomycin non-susceptible S. aureus in MRSA with the vancomycin MIC of 2 μg/ml also appeared ,. In the surveillance of S. aureus, hVISA, VISA, VRSA, LRSA and daptomycin non-susceptible S. aureus are of current interest.
S. pneumoniae is the major cause of invasive bacterial diseases (meningitis and pneumonia) in children less than five years . As a result, early diagnosis and antimicrobial susceptibility profile are essential for early and effective treatment. The most common antibiotics widely used for the treatment of invasive pneumococcal infections are penicillin and cefotaxime. The penicillin and cefotaxime susceptibility among isolates from meningitis in children was 83 and 97 per cent, respectively and in non-meningitis 100 per cent for both the antibiotics .
The overall susceptibility of S. pneumoniae to penicillin and cefotaxime among children was between 86-92 per cent and 92-100 per cent whereas in adults it was 91 and 94 per cent, respectively. In children, the percentage susceptibility to erythromycin and co-trimoxazole were 59-64 and 0-43 per cent, respectively  (CMC 2017, unpublished data). Susceptibility was 96 per cent to levofloxacin. The overall susceptibility in adults for penicillin was 90 per cent, cefotaxime 92 per cent, erythromycin 44 per cent and co-trimoxazole is 0 per cent; 100 per cent susceptibility was seen for vancomycin and linezolid across all age groups (CMC 2017, unpublished data). High penetration of moxifloxacin, (4th-generation fluoroquinolone), in epithelial-lining fluid and alveolar macrophages makes it more effective against S. pneumoniae than gatifloxacin, levofloxacin, ofloxacin and ciprofloxacin in respiratory infections .
According to the 2018 European Committee for Antimicrobial Susceptibility Testing (EUCAST) guidelines , the susceptibility zone diameter of oxacillin has been changed to 20 mm and an algorithm has to be followed. In meningitis, the resistance to penicillin is reported if the oxacillin zone size is below 20 mm, and further penicillin MIC has to be done. In case of inhibition zone more than 20 mm, it is considered susceptible to all β-lactams except for cefaclor which is intermediate. Susceptibility to antibiotics such as ampicillin, amoxicillin and piperacillin with or without inhibitors and cefepime, cefotaxime, ceftaroline, ceftobiprole, ceftriaxone can be reported if the oxacillin zone is ≥8 mm and MIC needs to be determined if <8 mm. For meropenem, two new breakpoints have been introduced, the breakpoints for meningitis is susceptible ≤0.25 and resistant >1 mg/l, and for non-meningitis ≤2 and >2, respectively .
The genetic basis of penicillin resistance in S. pneumoniae is mainly due to mutations in penicillin-binding proteins (PBPs). The mutations in the conserved motifs of the major proteins, PBP2b, PBP2x and PBP1a, lead to alteration in PBPs and thereby resistance . It has been reported that penicillin resistance in S. pneumoniae is due to the network of genes consisting of the three major PBPs and 10 other proteins. Within PBPs, there have been 161 sites associated with β-lactam resistance and coupling between sites in these genes constitutes changes in pneumococci and produces different susceptibility rates to β-lactams . Mutations in PBPs are seen in all isolates with penicillin MIC ≥0.12 μg/ml (CMC, unpublished data). The other factors of non PBP mediated resistance is through mur M and N, cia H, ftsl and gpB genes ,. The erythromycin resistance is due to mef( A/E) erm A/B and rarely due to ribosomal protein mutations in L4 and L22. erm(B) or the erm(A) genes give rise to high-level resistance- (MLSB type) and mef(A/E)-low-level resistance . mef A/E is more prevalent (56%) than erm B (29%) in Indian isolates (CMC, unpublished data). Fluoroquinolone resistance is attributed due to mutations in gyr A, gyr B genes (DNA gyrase) and topoisomerase IV (par C, par E genes) and the presence of efflux protein PmrA. parC mutation leads to low-level resistance and gyr A mutation leads to high-level resistance .
Enterococcus species are common in nosocomial infections and their incidence is rising. Treatment of enterococcal infections is complicated due to the high-resistance rates, with inherent resistance to cephalosporins and an increasing prevalence of ampicillin and vancomycin resistance is reported. Among the Enterococcus spp., E. faecium is isolated at much higher rates than E. faecalis. It is highly important to identify the species, as resistance rates are more commonly seen in E. faecium than E. faecalis and treatment strategy must be species specific. Among the antimicrobials tested, ampicillin resistance is seen at higher rates ,,.
Antimicrobial susceptibility profile for Enterococcus spp. was as follows: ampicillin (3-35%; IQR: 11-34), high-level gentamicin (16-89%; IQR: 26-71), vancomycin (77-100%; IQR: 80-93) and linezolid (98-100%; IQR: 99-100). Overall, vancomycin resistance was reported to be around 20 per cent. Molecular mechanism of vancomycin resistance is due to different genes namely VanA, VanB, VanC, VanD, VanE and VanG. In India, 91 per cent of the vancomycin resistance phenotypes are reported to be mediated by VanA gene, which confers high-level resistance. The second predominant is VanC 1 gene, showing intrinsic low-level resistance to vancomycin .
| Gram-Negative Organisms|| |
E. coli represents a major cause of morbidity and mortality worldwide. The treatment of E. coli infections is complicated due to the emergence of antimicrobial resistance. E. coli species are being increasingly resistant to commonly prescribed antibiotics in many settings. The antimicrobial susceptibility pattern of E. coli observed was amoxicillin/clavulanic acid (11-38%), cefotaxime (14-76%; IQR: 19-60), ceftazidime (7-50%; IQR: 12-37), piperacillin+tazobactum (21-89%; IQR: 25-67), cefperazone+sulbactam (88-100%), imipenem (43-100%; IQR: 68-97), meropenem (67-89%; IQR: 71-86), amikacin (27-88%; IQR: 28-88), gentamicin (21-86%; IQR: 22-63), ciprofloxacin (15-67%; IQR: 22-49), levofloxacin (13-25%) and colistin (97-100%; IQR: 98-100),,,,,,,.
One of the most important mechanisms of resistance observed in E. coli is the production of extended-spectrum β-lactamase enzymes (ESBL). The ESBL-producing strains are of particular concern as these are resistant to all penicillins and cephalosporins. Among these ESBLs, TEM (40-72%) and CTX-M (60-79%) types are more prevalent ,. Of the different CTX-M–type ESBLs, CTX-M-15 has become the most widely disseminated enzyme worldwide. It was first identified in an isolate from India in 1999 and subsequently became prevalent around the world .
Resistance to carbapenems among E. coli is of particular importance as these agents are often the last line of effective therapy. New Delhi metallo-β-lactamase (NDM) and carbapenem-hydrolyzing oxacillinase-48 (OXA48-like) are the most common carbapenemases reported in E. coli with the prevalence rate of 38-92 and 15-26 per cent, respectively . The less commonly seen were KPC, VIM and IMP genes.
Recently, emerging reports of plasmid-mediated colistin resistance, mcr genes in E. coli is alarming . Polymyxins (colistin and polymyxin B) are the last-resort antibiotics for treating infections caused by carbapenemase producers . Notably, mcr-1, mcr-2, mcr-3 and mcr-4 genes were first reported in E. coli. Further, genes encoding resistance to tetracycline (tet A - 38%, tet B - 43%), trimethoprim (dfr A1 - 8%, dfr A17 - 45%), sulphonamides (sul 1 - 70%, sul 2 - 25%), chloramphenicol (cat A1 - 8%, cat B3 - 13%, cat B4 - 50%), streptomycin (str A/B - 5%) and plasmid mediated quinolone resistance determinants such as aac(6')-lb-cr (58%), qnr B1 (3%), and qnr S1 (5%) were reported in E. coli (CMC, unpublished data).
Monitoring trend of antimicrobial resistance among K. pneumoniae is essential for antimicrobial stewardship programmes. High rates of ESBL have been reported in India from various centers with susceptibility ranging from 10 to 60 per cent (IQR: 12-50),. Susceptibility to carbapenems showed diverse range from 44 to 72 per cent (IQR: 55-72) in the last few years . Susceptibility to amikacin has been 65 per cent over the past three years while gentamicin susceptibility was 55 per cent (CMC, unpublished data). At present, 37 per cent of the carbapenem-resistant K. pneumoniae is resistant to colistin is observed (CMC, unpublished data).
Molecular characterization of β-lactamases in India has shown that among ESBLs, coexpression of blaSHV, blaTEM and blaCTX-M are common ,. The prevalence of blaSHVranged from 16 to 45 per cent; blaTEM7 to 47 per cent and blaCTX-M from 37 to 43 per cent. blaNDM had a prevalence ranging from 7 to 70 per cent and blaOXA48-like13 up to 55 per cent. These are the common carbapenem resistant genes ,,. blaVIM has been reported up to 18 per cent of the isolates . blaKPC has been seldom reported from India .
Diverse mechanisms coding for aminoglycosides include AMEs and 16 S RMTases. aadA2, aadA4 are the common AMEs and rmtF and armA are the frequently seen in India (CMC, unpublished data). However, tigecycline resistance encoded by efflux pumps with overexpression of ramA gene and AcrAB efflux pump has been reported . Colistin resistance is mostly chromosomal among clinical specimens while a single report of plasmid-mediated mcr gene among environmental sample has been documented . Chromosomal mutations reported have been in mgrB, phoP, phoQ and pmrB.
Shigella species include four serogroups: S. dysenteriae, S. flexneri, S. sonnei and S. boydii. All four Shigella spp. may cause disease, S. flexneri with serotype 2a being the most commonly isolated serotype followed by S. sonnei in India. However, S. dysenteriae and S. boydii were less frequently isolated .
Multidrug-resistant Shigellae reported worldwide range from 36 to 98 per cent. In India, the antimicrobial susceptibility profile observed were, ampicillin (0-68%; IQR: 2-43), trimethoprim-sulphamethoxazole (0-33%; IQR: 5-27), chloramphenicol (30-90%; IQR: 44-75), tetracycline (2-70%; IQR: 6-34), nalidixic acid (0-66%; IQR: 4-41), ciprofloxacin (10-94%; IQR: 16-82), norfloxacin (14-94%; IQR: 22-95), ofloxacin (6-90%; IQR: 13-43) and cefixime (0-95%),,,,,,,,. Notably, changing trend was observed for ampicillin susceptibility between the species S. flexneri and S. sonnei. Ampicillin susceptibility was lesser in S. flexneri when compared to S. sonnei. The susceptibility profile of other antibiotics remained unchanged. Besides, there was a rising trend in the ESBL rates among Shigella spp. (8-19%).
Among β-lactam resistance in Shigella spp., ampicillin resistance was encoded by OXA and TEM type β-lactamases. Resistance was predominantly due to blaOXA-1(30-100%) followed by blaTEM-1 (20-100%)(CMC, unpublished data). While for cephalosporin resistance, CTX-M-type β-lactamases blaCTX-M-15, is the most common variant seen in India, to date, blaCTX-M-15, blaCTX-M-14, blaCTX-M-3 and blaCMY-2 genes have been reported .
Quinolone resistance in Shigella involves the accumulation of mutations in DNA gyrase and DNA topoisomerase IV and plasmid-mediated quinolone resistance (PMQR) determinants such as qnrA, qnrB, qnrS and aac(6)-Ib-cr genes which confer low-level resistance to quinolones. The varying prevalence rates of these genes were reported in several studies from India ,,. The trimethoprim-sulphamethoxazole resistances was due to dhfr1A gene (75-80%) followed by the sulII gene (70%) (CMC, unpublished data). Reports of Shigella resistant to azithromycin have been documented . The genes that encode macrolide resistance were identified to be mphA and ermB. Resistance to chloramphenicol, tetracycline and streptomycin has mainly been attributed to the presence of cat (18-32%), tet (40-90%) and str (60%) genes (CMC, unpublished data).
| Typhoidal and Non-Typhoidal Salmonella|| |
Enteric fever is an endemic disease in India caused by Salmonella enterica serovar Typhi and Paratyphi with S. Typhi being the predominant. The major challenge in enteric fever at present is the increase in antimicrobial resistance in both S. Typhi and S. Paratyphi A. In S. Typhi, the antimicrobial susceptibility profile seen for different antimicrobials were, ampicillin (62-97%; IQR: 85-95), co-trimoxazole (73-98%; IQR: 82-97), chloramphenicol (78-98%; IQR: 90-97), nalidixic acid (0-24%; IQR: 0-19), ciprofloxacin (0-81%; IQR: 2-71), ceftriaxone (64-100%; IQR: 81-100), cefixime (98-100%) and azithromycin (52-97%; IQR: 72-94). For S. Paratyphi A, antimicrobial susceptibility profile reported ampicillin (71-100%; IQR: 84-100), co-trimoxazole (71-100%; IQR: 92-100), chloramphenicol (73-100%; IQR: 87-100), nalidixic acid (0-6%; IQR: 0-4), ciprofloxacin (0-80%; IQR: 2-54), ceftriaxone (46-100%; IQR: 71-100) and azithromycin (50-100%),,,,,,,, (CMC, unpublished data).
There is a downward trend in the MDR rates, declined from 26 per cent in 2004 to 1 per cent in 2017 (CMC, unpublished data). However, high-level resistance to fluoroquinolones was also observed. Among quinolone resistance in typhoidal Salmonella, the most common chromosomal mutations found in DNA gyrase and topoisomerase gene were at codon 83 and at codon 87,. Plasmid-mediated quinolone resistance (PMQR) genes documented were qnr B (57-100%) and aac (6)-Ib-cr (5-17%).
Emergence of resistance to cephalosporin has also been documented. Resistance due to extended-spectrum β-lactamases (ESBLs) and AmpC is the major mechanism seen in Salmonella. Among ESBLs, TEM, SHV, PER, CTX-M families were reported with TEM and CTX-M being the most common. CMY-2 gene is the most predominant gene among AmpC β-lactamases. Other genes, such as cat, sul and str encode resistance for chloramphenicol, co-trimoxazole and streptomycin were also reported . Non-typhoidal salmonellosis (NTS) refers to the infections caused by all the serotypes of Salmonella except S. Typhi, Paratyphi A, Paratyphi B, Paratyphi C and Sendai. Multidrug-resistant NTS has become a global concern now. Among NTS, susceptibility was observed for ampicillin (0-93%; IQR: 6-67), co-trimoxazole (42-93%; IQR: 54-83), chloramphenicol (45-100%; IQR: 64-100), nalidixic acid (23-76%), ciprofloxacin (9-100%; IQR: 31-88), ceftriaxone and azithromycin (>90%),, (CMC, unpublished data). The most common types of ESBLs encountered in NTS were CTX-M and TEM (54%). Common among TEM group of ESBLs are TEM-3, TEM-27 and TEM-52.
Pseudomonas aeruginosa causes severe nosocomial infections leading to high morbidity and mortality rates. Centers for Disease Control and Prevention (CDC) has prioritized P. aeruginosa in serious threats category due to its multidrug resistance phenomenon . It is well known for its antimicrobial resistance due to its complex intrinsic resistance mechanisms.
Antimicrobial resistance in P. aeruginosa varies across different regions in India. Susceptibility to anti-pseudomonal are as follows: cephalosporins: ceftazidime/cefepime (31-76%; IQR: 32-66), piperacillin/tazobactam (36-76%; IQR: 37-75), carbapenems: imipenem/meropenem(33-73%; IQR: 43-66), fluoroquinolones: ciprofloxacin/ levofloxacin (29-75%; IQR:33-68), aminoglycosides: amikacin/gentamicin (32-80%; IQR: 35-71) and colistin (99-100%; IQR: 99-100). Overall, multidrug-resistant (MDR) rates range from 20-25 per cent ,,,.
Molecular mechanism of antimicrobial resistance in P. aeruginosa is diverse. Screening of β-lactamases from MDR P. aeruginosa collected across India showed 30-40 per cent of positivity . The most common being blaVEB(12-100%), blaTEM (3-10%) and less of blaSHV(1%) genes among ESBLs which confer resistance to anti-pseudomonal cephalosporins. blaGES(6-12%) in Class A carbapenemases, blaVIM(24-57%) followed by blaNDM(8-19%) and blaIMP(4-5%) in Class B carbapenemases (metallo-β-lactamases) confer carbapenem resistance. Although carbapenemases are seen in P. aeruginosa isolates across India, a typical observation is of blaNDM being more in southern India, while blaVIM being more in northern part of India . AmpC de-repression phenotype is seen among 80 per cent of carbapenem-resistant isolates with no carbapenemase production .
Acinetobacter species have become a leading cause of nosocomial infections. Acinetobacter calcoaceticus-baumannii group (Acb complex) includes six species, A. baumannii, A. pittii, A. nosocomialis, A. seifertii, A. dijkshoorniae and A. calcoaceticus. To differentiate Acinetobacter species, OXA-51 alone may not be sufficient. gyrB multiplex PCR and rpoB sequencing will help accurately identify species within the Acb complex. Bruker MALDI-TOF Biotyper system with updated database allows successful delineation of Acinetobacter species .
The susceptibility profile ranged against ceftazidime (0-79%; IQR: 14-31), piperacillin-tazobactam (10-66%; IQR: 13-44) imipenem (20-71%; IQR: 30-60), meropenem (10-73%; IQR: 24-49), amikacin (15-61%; IQR: 17-55), tobramycin (38-84%; IQR: 41-63), netilmicin (35-77%; IQR: 36-65) and colistin (78-100%; IQR: 86-99),,,,,, (ICMR-AMRSN, unpublished data).
Among β-lactam resistance, blaPER-like(41-76%) gene is most predominantly reported followed by blaTEM like(8-87%). Carbapenem resistance in A. baumannii is predominantly mediated by class D carbapenemase blaOXA-23-like(42-99%) followed by Class B metallo-β-lactamase blaNDM-like(14-60%), blaVIM-like(1-59%) and blaIMP-like(36-55%),,,,.
Aminoglycoside resistance in A. baumannii is mainly due to AMEs and 16S rRNA methyltransferases (RMTase). AMEs such as aac (6), ant (2) and aph (3) were reported in 47.8, 17.4 and 8.7 per cent, respectively  in A. baumannii. The most common RMTase gene reported is armA (96.5%) followed by combination of armA with rmtB (3.5%) (CMC, unpublished data).
Colistin resistance in A. baumannii can be due to mutations in lipid A biosynthesis genes and point mutations in Pmr AB two-component regulatory system (TCS). Chromosomal mutations in lpxA, lpxD, lpsB and pmrB genes have also been observed (CMC, unpublished data).
| Conclusion|| |
Antimicrobial resistance is a growing public health concern across the globe. Resistance is seen at higher rates in Gram-negative organisms than Gram-positives. Diverse molecular resistance mechanisms have been reported in Gram-negative organisms which include high ESBL rates in E. coli, K. pneumoniae; high carbapenem and colistin resistance in K. pneumoniae and increased carbapenem resistance rates in A. baumannii than in P. aeruginosa. Among Gram-positive organisms, S. aureus with high rates of inducible clindamycin resistance in MRSA compared to MSSA were observed. Increasing incidence of penicillin non-susceptible S. pneumoniae (PNSP) is alarming. Emergence of resistance to third generation cephalosporins and macrolides are also observed in enteric pathogens such as Shigella and non-typhoidal Salmonella. This indicates the need for continuous monitoring of AMR to document any changing trends in the near future. Although information has been retrieved from the available hospital based literature, there is still a lacuna with the current national surveillance systems due to the limited network sites. Improved surveillance networks including multiple sites across different geographical locations would enable improved data collection to derive the true burden of AMR at a national level.
Financial support & sponsorship: The study was supported by the Indian Council of Medical Research, New Delhi.
Conflicts of Interest: None.
| References|| |
Indian Network for Surveillance of Antimicrobial Resistance (INSAR) group, India. Methicillin resistant Staphylococcus aureus
(MRSA) in India: Prevalence & susceptibility pattern. Indian J Med Res
Abbas A, Nirwan PS, Srivastava P. Prevalence and antibiogram of hospital acquired-methicillin resistant Staphylococcus aureus
and community acquired methicillin resistant Staphylococcus aureus
at a tertiary care hospital National Institute of Medical Sciences. Community Acquir Infect
Rajkumar S, Sistla S, Manoharan M, Sugumar M, Nagasundaram N, Parija SC, et al.
Prevalence and genetic mechanisms of antimicrobial resistance in Staphylococcus
species: A multicentre report of the Indian Council of Medical Research antimicrobial resistance surveillance network. Indian J Med Microbiol
Moolchandani K, Sastry AS, Deepashree R, Sistla S, Harish BN, Mandal J. Antimicrobial resistance surveillance among intensive care units of a tertiary care hospital in Southern India. J Clin Diagn Res
Perumal N, Murugesan S, Krishnan P. Distribution of genes encoding aminoglycoside-modifying enzymes among clinical isolates of methicillin-resistant staphylococci. Indian J Med Microbiol
Lall M, Sahni AK. Prevalence of inducible clindamycin resistance in Staphylococcus aureus
isolated from clinical samples. Med J Armed Forces India
Sasirekha B, Usha MS, Amruta JA, Ankit S, Brinda N, Divya R. Incidence of constitutive and inducible clindamycin resistance among hospital-associated Staphylococcus aureus. 3 Biotech
Mokta KK, Verma S, Chauhan D, Ganju SA, Singh D, Kanga A, et al.
Inducible clindamycin resistance among clinical isolates of Staphylococcus aureus
from Sub Himalayan region of India. J Clin Diagn Res
Abbas A, Srivastava P, Nirwan PS. Prevalence of MLSB resistance and observation of erm
A & erm
C genes at A tertiary care hospital. J Clin Diagn Res
Majhi S, Dash M, Mohapatra D, Mohapatra A, Chayani N. Detection of inducible and constitutive clindamycin resistance among Staphylococcus aureus
isolates in a tertiary care hospital, Eastern India. Avicenna J Med
Banik A, Khyriem AB, Gurung J, Lyngdoh VW. Inducible and constitutive clindamycin resistance in Staphylococcus aureus
in a northeastern Indian tertiary care hospital. J Infect Dev Ctries
Singh T, Deshmukh AB, Chitnis V, Bajpai T. Inducible clindamycin resistance among the clinical isolates of Staphylococcus aureus
in a tertiary care hospital. Int J Health Allied Sci
Singh A, Prasad KN, Misra R, Rahman M, Singh SK, Rai RP, et al.
Increasing trend of heterogeneous vancomycin intermediate Staphylococcus aureus
in a tertiary care center of Northern India. Microb Drug Resist
Chaudhari CN, Tandel K, Grover N, Sen S, Bhatt P, Sahni AK. Heterogeneous vancomycin-intermediate among methicillin resistant Staphylococcus aureus
. Med J Armed Forces India
Bakthavatchalam YD, Veeraraghavan B, Peter JV, Rajinikanth J, Inbanathan FY, Devanga Ragupathi NK, et al.
Novel observations in 11 heteroresistant vancomycin-intermediate methicillin-resistant Staphylococcus aureus
strains from South India. Genome Announc
. pii: e01425-16.
Bakthavatchalam YD, Veeraraghavan B, Devanga Ragupathi NK, Babu P, Munuswamy E, David T, et al.
Draft genome sequence of reduced teicoplanin-susceptible and vancomycin-heteroresistant methicillin-resistant Staphylococcus aureus
from sepsis cases. J Glob Antimicrob Resist
Gowrishankar S, Thenmozhi R, Balaji K, Pandian SK. Emergence of methicillin-resistant, vancomycin-intermediate Staphylococcus aureus
among patients associated with group A streptococcal pharyngitis infection in Southern India. Infect Genet Evol
Zhang S, Sun X, Chang W, Dai Y, Ma X. Systematic review and meta-analysis of the epidemiology of vancomycin-intermediate and heterogeneous vancomycin-intermediate Staphylococcus aureus
isolates. PLoS One
Walters MS, Eggers P, Albrecht V, Travis T, Lonsway D, Hovan G, et al
. Vancomycin-resistant Staphylococcus aureus
-Delaware, 2015. MMWR Morb Mortal Wkly Rep
McGuinness WA, Malachowa N, DeLeo FR. Vancomycin resistance in Staphylococcus aureus
. Yale J Biol Med
Ma XX, Wang EH, Liu Y, Luo EJ. Antibiotic susceptibility of coagulase-negative staphylococci (CoNS): Emergence of teicoplanin-non-susceptible CoNS strains with inducible resistance to vancomycin. J Med Microbiol
Kumar M. Multidrug-resistant Staphylococcus aureus
, India, 2013-2015. Emerg Infect Dis
Rai S, Niranjan DK, Kaur T, Singh NP, Hada V, Kaur IR, et al.
Detection of the classical G2576U mutation in linezolid resistant Staphylococcus aureus
along with isolation of linezolid resistant Enterococcus faecium
from a patient on short-term linezolid therapy:First report from India. Indian J Med Microbiol
Vamsimohan A, Gupta S, Muralidharan S. Daptomycin resistance in methicillin-resistant Staphylococcus aureus
: A report from Southern India. Germs
Jain S, Gaind R, Chugh TD. In vitro
activity of vancomycin and daptomycin against clinical isolates of Staphylococcus aureus
and enterococci from India. Int J Antimicrob Agents
Manoharan A, Manchanda V, Balasubramanian S, Lalwani S, Modak M, Bai S, et al.
Invasive pneumococcal disease in children aged younger than 5 years in India: A surveillance study. Lancet Infect Dis
Robinson KA, Baughman W, Rothrock G, Barrett NL, Pass M, Lexau C, et al.
Epidemiology of invasive Streptococcus pneumoniae
infections in the United States, 1995-1998: Opportunities for prevention in the conjugate vaccine era. JAMA
Nightingale CH. Moxifloxacin, a new antibiotic designed to treat community-acquired respiratory tract infections: A review of microbiologic and pharmacokinetic-pharmacodynamic characteristics. Pharmacotherapy
Barcus VA, Ghanekar K, Yeo M, Coffey TJ, Dowson CG. Genetics of high level penicillin resistance in clinical isolates of Streptococcus pneumoniae
. FEMS Microbiol Lett
Skwark MJ, Croucher NJ, Puranen S, Chewapreecha C, Pesonen M, Xu YY, et al.
Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis. PLoS Genet
Chewapreecha C, Marttinen P, Croucher NJ, Salter SJ, Harris SR, Mather AE, et al.
Comprehensive identification of single nucleotide polymorphisms associated with beta-lactam resistance within pneumococcal mosaic genes. PLoS Genet
Hakenbeck R, Grebe T, Zähner D, Stock JB. Beta-lactam resistance in Streptococcus pneumoniae
: Penicillin-binding proteins and non-penicillin-binding proteins. Mol Microbiol
Schroeder MR, Stephens DS. Macrolide resistance in Streptococcus pneumoniae
. Front Cell Infect Microbiol
Eliopoulos GM. Quinolone resistance mechanisms in pneumococci. Clin Infect Dis
(Suppl 4) : S350-6.
Wattal C, Raveendran R, Goel N, Oberoi JK, Rao BK. Ecology of blood stream infection and antibiotic resistance in Intensive Care Unit at a tertiary care hospital in North India. Braz J Infect Dis
Sachan S, Rawat V, Umesh MK, Kumar M, Kaur T, Chaturvedi P. Susceptibility pattern of enterococci at tertiary care hospital. J Glob Infect Dis
Singh AK, Venkatesh V, Singh RP, Singh M. Bacterial and antimicrobial resistance profile of bloodstream infections: A hospital-based study. CHRISMED J Health Res
Praharaj I, Sujatha S, Parija SC. Phenotypic & genotypic characterization of vancomycin resistant Enterococcus
isolates from clinical specimens. Indian J Med Res
Purohit G, Gaind R, Dawar R, Verma PK, Aggarwal KC, Sardana R, et al.
Characterization of vancomycin resistant enterococci in hospitalized patients and role of gut colonization. J Clin Diagn Res
Gandra S, Mojica N, Klein EY, Ashok A, Nerurkar V, Kumari M, et al.
Trends in antibiotic resistance among major bacterial pathogens isolated from blood cultures tested at a large private laboratory network in India, 2008-2014. Int J Infect Dis
Pandita N, Wasim S, Bhat NK, Chandra V, Kakati B. Identification of the bacterial isolates in neonatal septicaemia and their antimicrobial susceptibility in a tertiary care hospital in Uttarakhand, India: A retrospective study. Int J Contemp Pediatr
Chaudhary BL, Srivastava S, Singh BN, Shukla S. Nosocomial infection due to multidrug resistant (MDR) Escherichia coli
and Klebsiella pneumoniae
in Intensive Care Unit. Int J Curr Microbiol Appl Sci
Vasudeva N, Nirwan PS, Shrivastava P. Bloodstream infections and antimicrobial sensitivity patterns in a tertiary care hospital of India. Ther Adv Infect Dis
Rajeevan S, Ahmad SM, Jasmin PT. Study of prevalence and antimicrobial susceptibility pattern in blood isolates from a tertiary care hospital in North Kerala, India. Int J Curr Microbiol Appl Sci
Arora A, Jain C, Saxena S, Kaur R. Profile of drug resistant Gram negative bacteria from ICU at a tertiary care center of India. Asian J Med Health
Radha Rani D, Chaitanya SB, Rajappa SJ, Basanth Kumar R, Prabhakar KK, Krishna Mohan MVT, et al
. Retrospective analysis of blood stream infections and antibiotic susceptibility pattern of Gram negative bacteria in a tertiary care cancer hospital. Int J Med Res Health Sci
Gupta S, Kashyap B. Bacteriological profile and antibiogram of blood culture isolates from a tertiary care hospital of North India. Trop J Med Res
Ranjan A, Shaik S, Mondal A, Nandanwar N, Hussain A, Semmler T, et al.
Molecular epidemiology and genome dynamics of New Delhi metallo-β-lactamase-producing extraintestinal pathogenic Escherichia coli
strains from India. Antimicrob Agents Chemother
Bora A, Hazarika NK, Shukla SK, Prasad KN, Sarma JB, Ahmed G, et al.
Prevalence of blaTEM
genes in clinical isolates of Escherichia coli
and Klebsiella pneumoniae
from Northeast India. Indian J Pathol Microbiol
Dureja C, Mahajan S, Raychaudhuri S. Phylogenetic distribution and prevalence of genes encoding class I integrons and CTX-M-15 extended-spectrum β-lactamases in Escherichia coli
isolates from healthy humans in Chandigarh, India. PLoS One
Borowiak M, Fischer J, Hammerl JA, Hendriksen RS, Szabo I, Malorny B, et al.
Identification of a novel transposon-associated phosphoethanolamine transferase gene, mcr-5
, conferring colistin resistance in d-tartrate fermenting Salmonella enterica
subsp. enterica serovar Paratyphi B. J Antimicrob Chemother
Carattoli A, Villa L, Feudi C, Curcio L, Orsini S, Luppi A, et al
. Novel plasmid-mediated colistin resistance mcr-4
gene in Salmonella
and Escherichia coli
, Italy 2013, Spain and Belgium, 2015 to 2016. Euro Surveill
. Pii : 30589.
Veeraraghavan B, Shankar C, Karunasree S, Kumari S, Ravi R, Ralph R, et al.
Carbapenem resistant Klebsiella pneumoniae
isolated from bloodstream infection: Indian experience. Pathog Glob Health
Roy S, Gaind R, Chellani H, Mohanty S, Datta S, Singh AK, et al.
Neonatal septicaemia caused by diverse clones of Klebsiella pneumoniae
& Escherichia coli
. Indian J Med Res
Khajuria A, Praharaj AK, Kumar M, Grover N. Carbapenem resistance among Enterobacter
species in a tertiary care hospital in central India. Chemother Res Pract
Chaudhary M, Payasi A. Antimicrobial susceptibility patterns and molecular characterization of Klebsiella pneumoniae
clinical isolates from north Indian patients. Int J Med Med Sci
Roy S, Datta S, Viswanathan R, Singh AK, Basu S. Tigecycline susceptibility in Klebsiella pneumoniae
and Escherichia coli
causing neonatal septicaemia (2007-10) and role of an efflux pump in tigecycline non-susceptibility. J Antimicrob Chemother
Marathe NP, Pal C, Gaikwad SS, Jonsson V, Kristiansson E, Larsson DGJ, et al.
Untreated urban waste contaminates Indian river sediments with resistance genes to last resort antibiotics. Water Res
Pragasam AK, Shankar C, Veeraraghavan B, Biswas I, Nabarro LE, Inbanathan FY, et al.
Molecular mechanisms of colistin resistance in Klebsiella pneumoniae
causing bacteremia from India - A first report. Front Microbiol
Anandan S, Muthuirulandi Sethuvel DP, Gajendiren R, Verghese VP, Walia K, Veeraraghavan B, et al.
Molecular characterization of antimicrobial resistance in clinical Shigella
isolates during 2014 and 2015: Trends in South India. Germs
Bhattacharya D, Sugunan AP, Bhattacharjee H, Thamizhmani R, Sayi DS, Thanasekaran K, et al.
Antimicrobial resistance in Shigella
- Rapid increase & widening of spectrum in Andaman Islands, India. Indian J Med Res
Das A, Natarajan M, Mandal J. The emergence of quinolone resistant Shigella sonnei
, Pondicherry, India. PLoS One
Kumar A, Oberoi A, Alexander VS. Prevalence and antimicrobial susceptibility patterns of Shigella
in stool samples in a tertiary healthcare hospital of Punjab. CHRISMED J Health Res
Aggarwal P, Uppal B, Ghosh R, Jha AK, Konar D. Surveillance of changing antimicrobial resistance pattern in Shigella
in North India. Int J
Aggarwal P, Uppal B, Ghosh R, Krishna Prakash S, Chakravarti A, Jha AK, et al.
Multi drug resistance and extended spectrum beta lactamases in clinical isolates of Shigella
: A study from New Delhi, India. Travel Med Infect Dis
Shakya G, Acharya J, Adhikari S, Rijal N. Shigellosis in Nepal: 13 years review of nationwide surveillance. J Health Popul Nutr
Muthuirulandi Sethuvel DP, Devanga Ragupathi NK, Anandan S, Veeraraghavan B. Update on: Shigella
new serogroups/serotypes and their antimicrobial resistance. Lett Appl Microbiol
Kahsay AG, Muthupandian S. A review on sero diversity and antimicrobial resistance patterns of Shigella
species in Africa, Asia and South America, 2001-2014. BMC Res Notes
Taneja N, Mewara A, Kumar A, Verma G, Sharma M. Cephalosporin-resistant Shigella flexneri
over 9 years (2001-09) in India. J Antimicrob Chemother
Williams PCM, Berkley JA. Guidelines for the treatment of dysentery (shigellosis): a systematic review of the evidence. Paediatr Int Child Health
Taneja N, Mewara A. Shigellosis: Epidemiology in India. Indian J Med Res
Singhal L, Gupta PK, Kale P, Gautam V, Ray P. Trends in antimicrobial susceptibility of Salmonella typhi
from North India (2001-2012). Indian J Med Microbiol
Dutta S, Das S, Mitra U, Jain P, Roy I, Ganguly SS, et al.
Antimicrobial resistance, virulence profiles and molecular subtypes of Salmonella enterica
serovars typhi and paratyphi A blood isolates from Kolkata, India during 2009-2013. PLoS One
Narain U, Gupta R. Emergence of resistance in community-acquired enteric fever. Indian Pediatr
Tewari R, Jamal S, Dudeja M. Antimicrobial resistance pattern of Salmonella enterica
servars in Southern Delhi. Int J Community Med Public Health
Rudresh SM, Nagarathnamma T. Antibiotic susceptibility pattern of Salmonella enterica
serovar typhi and Salmonella enterica
serovar paratyphi A with special reference to quinolone resistance. Drug Dev Ther
Behl P, Gupta V, Sachdev A, Guglani V, Chander J. Patterns in antimicrobial susceptibility of salmonellae isolated at a tertiary care hospital in Northern India. Indian J Med Res
Jeeyani HN, Mod HK, Tolani JN. Current perspectives of enteric fever: A hospital based study of 185 culture positive cases from Ahmedabad, India. Int J Contemp Pediatr
Patel SR, Bharti S, Pratap CB, Nath G. Drug resistance pattern in the recent isolates of Salmonella typhi
with special reference to cephalosporins and azithromycin in the gangetic plain. J Clin Diagn Res
Dahiya S, Sharma P, Kumari B, Pandey S, Malik R, Manral N, et al.
Characterisation of antimicrobial resistance in Salmonellae
during 2014-2015 from four centres across India: An ICMR antimicrobial resistance surveillance network report. Indian J Med Microbiol
Veeraraghavan B, Pragasam AK, Bakthavatchalam YD, Ralph R. Typhoid fever: Issues in laboratory detection, treatment options & concerns in management in developing countries. Future Sci OA
Raveendran R, Wattal C, Sharma A, Oberoi JK, Prasad KJ, Datta S, et al.
High level ciprofloxacin resistance in Salmonella enterica
isolated from blood. Indian J Med Microbiol
Geetha VK, Yugendran T, Srinivasan R, Harish BN. Plasmid-mediated quinolone resistance in typhoidal salmonellae: A preliminary report from South India. Indian J Med Microbiol
Taneja N, Appannanavar SB, Kumar A, Varma G, Kumar Y, Mohan B, et al.
Serotype profile and molecular characterization of antimicrobial resistance in non-typhoidal Salmonella
isolated from gastroenteritis cases over nine years. J Med Microbiol
Oommen S, Nair S, Nair K, Pillai S. Epidemiology of non-typhoidal Salmonella
among patients attending a tertiary care centre in Central Kerala. J Acad Clin Microbiol
Maanasa BM, Harish BN. Drug resistance in nontyphoidal Salmonella
-challenges for the future. J Vet Med Res
Ahmed NH, Hussain T. Antimicrobial susceptibility patterns of leading bacterial pathogens isolated from laboratory confirmed blood stream infections in a multi-specialty sanatorium. J Glob Infect Dis
Santa A, Rao TS. Retrospective analysis of blood stream infections and antibiotic susceptibility pattern of Gram negative bacteria in a tertiary care cancer hospital. Health Sci
Rose W, Veeraraghavan B, George B. Bloodstream infections in children with febrile neutropenia: Isolates and their antimicrobial susceptibility profile. Indian J Cancer
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
Marí-Almirall M, Cosgaya C, Higgins PG, Van Assche A, Telli M, Huys G, et al.
MALDI-TOF/MS identification of species from the Acinetobacter baumannii
(Ab) group revisited: Inclusion of the novel A. seifertii
and A. dijkshoorniae
species. Clin Microbiol Infect
Shrivastava G, Bhatambare GS, Bajpai T, Patel KB. Sensitivity profile of multidrug resistant Acinetobacter
spp. isolated at ICUs of tertiary care hospital. Int J Health Syst Disaster Manage
Tripathi PC, Gajbhiye SR, Agrawal GN. Clinical and antimicrobial profile of Acinetobacter
spp.: An emerging nosocomial superbug. Adv Biomed Res
Saranathan R, Vasanth V, Vasanth T, Shabareesh PR, Shashikala P, Devi CS, et al
. Emergence of carbapenem non-susceptible multidrug resistant Acinetobacter baumannii
strains of clonal complexes 103(B) and 92(B) harboring OXA-type carbapenemases and metallo-β-lactamases in Southern India. Microbiol Immunol
Bimal KK, Das S, Kishore S, Shahi SK. Antimicrobial sensitivity of multidrug-resistant Acinetobacter baumannii
in a tertiary care hospital of Patna. J Evid Based Med Healthc
Pal N, Sujatha R. Evaluation of acute physiology and chronic health evaluation score II in Acinetobacter baumannii
infection/colonization and its antimicrobial resistance profile in Kanpur, India. Int J Curr Microbiol Appl Sci
Chaudhary M, Payasi A. Molecular characterization and antimicrobial susceptibility study of Acinetobacter baumannii
clinical isolates from Middle East, African and Indian patients. J Proteomics Bioinform
Niranjan DK, Singh NP, Manchanda V, Rai S, Kaur IR. Multiple carbapenem hydrolyzing genes in clinical isolates of Acinetobacter baumannii
. Indian J Med Microbiol
Vijayakumar S, Gopi R, Gunasekaran P, Bharathy M, Walia K, Anandan S, et al.
Molecular characterization of invasive carbapenem-resistant Acinetobacter baumannii
from a tertiary care hospital in South India. Infect Dis Ther
Khajuria A, Praharaj AK, Kumar M, Grover N. Molecular characterization of carbapenem resistant isolates of Acinetobacter baumannii
in an Intensive Care Unit of A tertiary care centre at central India. J Clin Diagn Res
Cai Y, Chai D, Wang R, Liang B, Bai N. Colistin resistance of Acinetobacter baumannii
: Clinical reports, mechanisms and antimicrobial strategies. J Antimicrob Chemother