To the Editor—The emergence and spread of antimicrobial drug resistance in Enterobacteriaceae is posing a serious threat to the treatment of nosocomial infections. Of particular importance are the pathogens of this family that produce metallo-β-lactamases (IMP-type carbapenemases [IMP], New Delhi metallo-β-lactamase, or Verona integron-encoded metallo-β-lactamase [VIM]), non-metallo enzymes (Klebsiella pneumoniae carbapenemase and Oxacillinase [OXA]-48), β-lactamases with a broad profile of substrate activity such as extended-spectrum β-lactamases, or AmpC enzyme with porin loss. Until recently, carbapenems have been successfully used for the treatment of infections caused by Enterobacteriaceae, including those producing extended-spectrum β-lactamases.Reference Falagas, Lourida, Poulikakos, Rafailidisa and Tansarli ¹ Antibiotic treatment options for these emerging carbapenem-resistant Enterobacteriaceae (CRE) are becoming limited.Reference Kelesidis, Karageorgopoulos, Kelesidis and Falagas ² Colistin and tigecycline have been reported as the remaining armamentarium against the species of Enterobacteriaceae.Reference Biswas, Brunel, Dubus, Reynaud-Gaubert and Rolain ^{3 ,} Reference Sader, Castanheira, Flamm, Mendes, Farrell and Jones ⁴ In the present study, a total of 210 clinically significant Enterobacteriaceae isolates were collected from various clinical samples of admitted patients (blood, urine, wound, and burn) over a period of 2 years (2013–2015). Susceptibility testing was performed by Clinical and Laboratory Standards Institute broth microdilution method, and isolates with a meropenem or imipenem minimum inhibitory concentration (MIC) of at least 4 mg/L were categorized as CRE. Escherichia coli ATCC 25922 was used as the control strain. Among these 210 isolates, 31 bacteria showed resistance to both imipenem (MIC ≥32 mg/L) and meropenem (MIC 32 mg/L). By means of 16S rRNA sequence of 31 CRE isolates, the following members of the Enterobacteriaceae family were identified: Enterobacter cloacae (5), Enterobacter aerogenes (4), Serratia marcescens (2), Providencia stuartii (2), Klebsiella pneumoniae (6), Citrobacter freundii (2), Proteus mirabilis (4), and E. coli (6). CRE are increasingly prevalent in many parts of the world.Reference Livermore, Warner, Mushtaq, Doumith, Zhang and Woodford ⁵ These CRE isolates were further screened for their resistance toward colistin (MIC 32–64 mg/L) and tigecycline (MIC 16-64 mg/L). All the strains of S. marcescens, K. pneumoniae, and E. coli showed resistance to both colistin and tigecycline (Figure 1). Resistance to colistin was 100% for all the strains of E. cloacae, P. stuartii, C. freundii, and P. mirabilis, whereas only 75% of strains of E. aerogenes were colistin resistant (Figure 1). A total of 80% of strains of E. cloacae and 75% of strains of P. mirabilis were resistant to tigecycline (Figure 1). Similarly, 50% of strains of E. aerogenes, P. stuartii, and C. freundii were tigecycline resistant (Figure 1). In the past few years, there have been sporadic reports of colistin-resistant CRE cases from various parts of the world, such as Greece, Israel, South Korea, United States, and Singapore,Reference Marchaim, Chopra and Pogue ⁶ and of tigecycline-resistant CRE.Reference Spanu, De Angelis and Cipriani ⁷ Colistin- and tigecycline-resistant CRE cases have never been reported from India. It should be further noted that co-resistance to both colistin and tigecycline among the CRE strains was not reported before.

FIGURE 1 Resistance pattern of carbapenem-resistant Enterobacteriaceae to last resort antibiotics. C. freundii, Citrobacter freundii; E. aerogenes, Enterobacter aerogenes; E. cloacae, Enterobacter cloacae; E. coli, Escherichia coli; K. pneumoniae, Klebsiella pneumoniae; P. mirabilis, Proteus mirabilis; P. stuartii, Providencia stuartii; S. marcescens, Serratia marcescens.

Thus, there is clearly a need for the development and screening of new antimicrobial agents to keep pace with the development and spread of drug resistance mechanisms in the Enterobacteriaceae family.