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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 4  |  Page : 734-737
Evaluation of tigecycline activity in clinical isolates among Indian medical centers

Benjamin M Pulimood Laboratories for Infection, Immunity and Inflammation (BMPLIII);Department of Medicine Unit I and Infectious Disease, Christian Medical College, Vellore-632 004, Tamil Nadu, India

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Date of Web Publication27-Oct-2010


Background: Resistance to multiple antibiotics among Gram-positive cocci (GPC) and Gram negative bacilli (GNB) is high in India. Tigecycline, a glycylcycline antibiotic is a newer treatment option for emerging single or multidrug-resistant (MDR) GPC and GNB. Material and Method: We evaluated the in vitro activity of tigecycline and compared it against other antimicrobials. Between 2005-2007, seven Indian medical centers from diverse geographic regions forwarded 727 isolates [Escherichia coli (166), Staphylococcus aureus (125), Klebsiella spp (120), Streptococcus pneumoniae (102), Enterococcus spp. (100), Pseudomonas aeruginosa (50), Acinetobacter spp. (50) and Enterobacter spp. (14)] from patients with blood stream (BSI), skin and soft tissue (SSTI) including surgical site, urinary tract and respiratory infections to our reference laboratory. Susceptibility to 11 antimicrobials besides tigecycline included: vancomycin, linezolid, teicoplanin, quinopristin-dalfopristin, daptomycin, amikacin, imipenem, levofloxacin, meropenem, and piperacillin/tazobactam was determined by agar dilution and Etest method. Result: Tigecycline was active against all GPC (MIC 90 < 0.25 μg/ml), E. coli and Klebsiella spp. (MIC 90 ≤1 μg/ml). MDR Acinetobacter spp. showed lower susceptibility (70.6%) to tigecycline. Tigecycline MIC 90 values were not influenced by oxacillin resistance among S. aureus, S. pneumoniae, vancomycin resistance in Enterococci (VRE) and ESBL producing E. coli, Klebsiella spp. and Enterobacter spp. Increased resistance was seen to other antimicrobials among ESBL producing E. coli, Klebsiella spp., Metallo Beta Lactamase (MBL) producing P. aeruginosa and VRE. Conclusion: Tigecycline is an alternative option for emerging multidrug-resistant (MDR) pathogens exhibiting promising spectrum/potency exceeding currently available agents seen in India.

Keywords: Antibiotic resistance, antibiotic susceptibility, tigecycline

How to cite this article:
Manoharan A, Chatterjee S, Madhan S, Mathai D. Evaluation of tigecycline activity in clinical isolates among Indian medical centers. Indian J Pathol Microbiol 2010;53:734-7

How to cite this URL:
Manoharan A, Chatterjee S, Madhan S, Mathai D. Evaluation of tigecycline activity in clinical isolates among Indian medical centers. Indian J Pathol Microbiol [serial online] 2010 [cited 2021 Aug 5];53:734-7. Available from: https://www.ijpmonline.org/text.asp?2010/53/4/734/72061

   Introduction Top

Resistance to currently available antibiotics is increasing at an alarming rate. At the same time, the development of new antimicrobial agents to treat serious bacterial infections is decreasing. As a result of the emergence and spread of multidrug resistance (MDR) in many pathogenic bacterial species, the need for new antimicrobial agents is more urgent and greater than ever. [1]

Tigecycline (9-t-butylglycylamido-minocycline) is a newer glycylcycline antimicrobial agent that induces its bacteriostatic effect by binding to a single high affinity intracellular site of the bacterial 30S ribosome. Tigecycline has potent in vitro activity against most Gram-positive and Gram-negative aerobic and anaerobic bacteria including S. aureus, Enterococcus spp., S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, peptostreptococci, Clostridium spp., Enterobacteriaceae and Bacteroides spp. Tigecycline has limited activity against Pseudomonas aeruginosa, and reduced activity against Proteus mirabilis. Tigecycline is very active against bacteria resistant to other classes of antibiotics, including the quinolones and beta-lactams. Tigecycline, additionally, resists deactivation by most known tetracycline resistance mechanisms. Because of this promising profile against clinically important bacteria, as well as promising pharmacodynamic and pharmacokinetic data, tigecycline is a good alternative to treat MDR pathogens. [1],[2],[3]

As part of our ongoing multicentric studies, we evaluated the in vitro efficacy of tigecycline against a spectrum of gram negative and gram positive pathogens and compared its activity against other commonly used antimicrobials.

   Materials and Methods Top

Bacterial Isolates

In the period from 2005-2007, seven medical centers forwarded 727 non duplicate (GNB=400, GPC=327) isolates from SSTI (n=216), BSI (n=184), sputum (n=99), Urine (n=46), CSF (n=21) and others (n=161; included CSF, nasopharyngeal aspirate, feces and fluids) to our reference laboratory. Tested isolates included; Escherichia coli (166), Staphylococcus aureus (125), Klebsiella spp (120), Streptococcus pneumoniae (102), Enterococcus spp. (100), Pseudomonas aeruginosa (50), Acinetobacter spp. (50) and Enterobacter spp (14). S.pneumoniae isolates were collected as part of the invasive bacterial infection surveillance (IBIS) 1993-2002 study at our center. ESBL and Non ESBL screening was done for Enterobacteriaceae according to Clinical Laboratory Standards Institute (CLSI 2007) guidelines. [4]

Antimicrobial Susceptibility Testing

Minimum Inhibitory Concentration (MIC) was determined against 11 antimicrobials besides tigecycline (GPC group: vancomycin, linezolid, teicoplanin, quinopristin-dalfopristin (QDA), daptomycin); (GNB group: amikacin, imipenem, levofloxacin, meropenem and piperacillin/tazobactam) by Etest method (bioMerieux Marcy l'Etoile, France). MIC to tigecycline was determined by agar dilution (pure substance provided by Wyeth Pharmaceuticals, Mumbai, India) and by E test. Interpretative criteria used were as per Etest manufacturer's guidelines and CLSI 2007. [4] The interpretation for tigecycline agar dilution MIC was done as per US FDA tigecycline breakpoints. ATCC 25922 E. coli, ATCC 29213 S.aureus, ATCC 27853 P. aeruginosa, ATCC 25923 S.aureus, ATCC 29212 E. faecalis were used as quality control strains.

   Results Top

[Table 1] shows the activities of tigecycline and the comparator antimicrobials. Tigecycline was uniformly active against all E. coli (MIC 90 =0.19μg/ml), Klebsiella spp (MIC 90 =1.0μg/ml) and Enterobacter spp (MIC 90 =0.5μg/ml). Majority (90.9%) of the Enterobacteriaceae were ESBL producers. Amikacin and Piperacillin/Tazobactam show good susceptibility against E.coli (94%, 85.4%) and Klebsiella spp. (85.5%, 73.4%), all strains were uniformly susceptible to imipenem and meropenem. All the isolates of S. aureus, S. pneumoniae, Enterococcus spp were susceptible (100%) to tigecycline and daptomycin. S. pneumoniae was susceptible to all tested drugs against Enterococcus spp. in vitro susceptibility of tigecycline (100%) > linezolid (92%) > quinopristin-dalfopristin (65%) > teicoplanin (47%) > vancomycin (37%). Tigecycline was potent against Methicillin resistant S. aureus (MRSA) (n=119; MIC 90 =0.19μg/ml) and VRE (n=63; MIC range =0.016-0.125μg/ml) [Table 1]. Increased resistance was seen to other antimicrobials for ESBL producing E. coli, Klebsiella spp., MBL producing P. aeruginosa and VRE.
Table 1 :In vitro activity of 11 antimicrobials in comparison to tigecycline against 727 clinical isolates from seven Indian medical centers

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   Discussion Top

Tigecycline shows high potency against Gram-negative bacilli belonging to family Enterobacteriaceae in whom multi-drug resistant strains have emerged as important nosocomial pathogens. Tigecycline's expanded, broad-spectrum activity is further evidenced by its activity against Legionella pneumophilia, Chlamydia, rapidly growing non-tuberculosis bacteria and various anaerobes such as Nocardia, Bacteroides and Clostridia species.[5]

Tigecycline is highly active against Enterobacteriaceae, regardless of the presence or absence of ESBLs [1],[2],[3] with MIC 90 values of ≤2 mg/L, >99% of all of the tested strains were inhibited at ≤4 mg/L. In the present study we found that tigecycline had good activity against tested E.coli and Klebsiella spp. (MIC 90≤1μg/ml).

Tigecycline is very active against other non-fermentative GNB, which includes Acinetobacter spp. (generally >90% susceptibility, with MICs <8 mg/L). [1] A recent study from India showed high prevalence of tigecycline resistance amongst Acinetobacter spp. which is worrisome since the organism is not only totally unexposed to tigecycline but also to the tetracycline group of antibiotics in Indian hospitals. [3] In our study among 17 MDR Acinetobacterspp. strain susceptibility to tigecycline was only 70.6%. In this study 94% of the P.aeruginosa strains were resistant to tigecycline, resistance to tigecycline by P. aeruginosa has been noted due to the effect of efflux pump. [6],[7] Tigecycline is not recommended for the treatment of infections caused by P. aeruginosa. The role of tigecycline as part of a combination regimen remains to be evaluated. [8]

The activity of tigecycline against staphylococci is completely unaltered by the presence of methicillin or glycopeptide resistance genes and remains fully effective against enterococci, expressing one or more vancomycin resistance determinants. It is the most potent antimicrobial when tested against glycopeptide-intermediately resistant S. aureus.[5] The potency of tigecycline was evident against both oxacillin susceptible and oxacillin-resistant S. aureus with the majority of investigations reporting an MIC 90 similar to our study (0.5 mg/L). [1] Tigecycline demonstrates excellent activity against most streptococci, including S. pneumoniae with reduced susceptibility or resistance to macrolides or beta-lactam antibiotics.

In our study, tigecycline was potent against MRSA (n=119; MIC 90 =0.19μg/ml) and VRE (n=63; MIC range =0.016-0.125μg/ml). Tigecycline and daptomycin were highly active (100% susceptible) against the three tested GPC. S.pneumoniae was pan susceptible to all tested drugs. A recent in vitro study shows that tigecycline has high in vitro activity against VRE and suggests that this drug may have an important role in the treatment of severely ill patients infected with VRE. [9] Tigecycline does not require dose adjustment in patients with impaired renal function and is conveniently administered every 12 h. [10] Tigecycline appears to have low potential for organ toxicity and drug-drug interactions. These properties, along with twice daily dosing and the lack of need to monitor renal function, make the use of this antibiotic relatively uncomplicated. One concern will be for patients who develop moderate-to-severe nausea and vomiting during tigecycline therapy. Since it has proven activity against highly resistant organisms, it should be reserved only for life-threatening situations and/or when resistant pathogens are suspected. Tigecycline's lack of activity against P. aeruginosa and low serum concentrations limits its use in some patient populations, such as those with neutropenic fever. [11]

The present study shows that tigecycline is a potent antimicrobial against MDR ESBL producing Enterobacteriaceae, VRE and MRSA. In summary, tigecycline could be valuable therapeutic option for the treatment of infections caused by MDR pathogens. Continued surveillance is necessary to generate local and epidemiological data on resistance profile of clinically important pathogens. This could also help in evaluating newer antimicrobial agents and guide rational antibiotic therapy.

   Acknowledgments Top

Authors are grateful to Christian Medical College Institutional Review Board for approving conduct of this study vide min no.6091 dated December 19, 2006. Dr. Kurien Thomas, IBIS study Principal Investigator is thanked for permitting use of S.pneumoniae collected as part of the IBIS study. Authors acknowledge receipt of an educational/research grant from Wyeth Pharmaceuticals, Mumbai.

   References Top

1.Pankey GA. Tigecycline. J Antimicrob Chemother 2005;56:470-80.  Back to cited text no. 1
2.Pachon-Ibanez ME, Jimenez-Mejias ME, Pichardo C. Activity of tigecycline (GAR-936) against Acinetobacter baumannii strains, including those resistant to imipenem. Antimicrob Agents Chemother 2004;48:4479-81.  Back to cited text no. 2
3.Behera B, Das A, Mathur P, Kapil A, Gadepalli R, Dhawan B. Tigecycline susceptibility report from an Indian tertiary care hospital. Indian J Med Res 2009;129:446-50.  Back to cited text no. 3
4.Clinical and Laboratory Standards Institute/NCCLS Performance Standards for Antimicrobial disc diffusion tests; Approved standards. 9 th ed. CLSI Document M2-A9, Wayne, PA: Clinical and Laboratory Standards Institute; 2007 .   Back to cited text no. 4
5.Felmingham D. Tigecyclin: The first glycylcycline to undergo clinical development: An overview of in vitro activity compared to tetracycline. J Chemother 2005;17:5-11.  Back to cited text no. 5
6.Dean CR, Visalli MA, Projan SJ, Sum PE, Bradford PA. Efflux-mediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1. Antimicrob Agents Chemother 2003;47:972-8.  Back to cited text no. 6
7.Visalli MA, Murphy E, Projan SJ, Bradford PA. AcrAB multidrug efflux pump is associated with reduced levels of susceptibility to tigecycline (GAR-936) in Proteus mirabilis. Antimicrob Agents Chemother 2003;47:665-9.  Back to cited text no. 7
8.Sum PE, Sum FW, Projan SJ. Recent developments in tetracycline antibiotics. Curr Pharm Des 1998;4:119-32.  Back to cited text no. 8
9.Yemisen M, Demirel A, Mete B, Kaygusuz A, Mert A, Tabak F, et al. Comparative in vitro antimicrobial activity of tigecycline against clinical isolates of vancomycin-resistant enterococcus. Indian J Med Microbiol 2009;27:373-4.  Back to cited text no. 9
[PUBMED]  Medknow Journal  
10.Gupta K, Kaushal S, Chopra SC. Tigecycline: A novel glycylcycline antibiotic. Indian J Pharmacol 2006;38:217-9.  Back to cited text no. 10
  Medknow Journal  
11.Stein GE, Craig WA. Tigecycline: A critical analysis. Clin Infect Dis 2006;43:518-24.  Back to cited text no. 11

Correspondence Address:
Anand Manoharan
Department of Medicine, Unit I and Infectious Diseases, Christian Medical College, Vellore-632 004, Tamil Nadu
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Source of Support: Wyeth Pharmaceuticals, Mumbai, Conflict of Interest: None

DOI: 10.4103/0377-4929.72061

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