Common causes of pediatric BSI and their antimicrobial resistance (AMR) patterns are highly variable across institutions [5]. Therefore, the surveillance of pathogens causing pediatric BSI and understanding their local epidemiology of AMR is an important prerequisite to predict empirical therapy. This study aimed to measure the prevalence of pathogens causing BSI in pediatric population of rural Southern India, and to measure the frequency of AMR in E.coli and Klebsiella spp. isolates.

This cross-sectional study was conducted at a tertiary care teaching hospital from January 2012 to December 2014. Blood culture specimens received for bacteriological investigation from pediatric (age 0 to 12 years) inpatients as part of their routine patient management were included in this study. The study protocol was approved by the Institutional Review Board of Government Theni Medical College.

Blood culture and the identification of isolate was performed as per the standard procedure [6]. The culture was considered contaminated when any of the following organisms was identified: Micrococcus spp., viridans streptococci, Bacillus spp., and diphtheroids [7].

Frequency of AMR was calculated by WHONET software and statistical analysis was performed with Chi-square test and the difference was considered significant when P value was less than 0.05.

A total of 1932 pediatric patients were tested by blood culture during the study period. Among them, 880 (45.5%) were positive with true pathogen (Table I), of which 38 and 102 isolates were identified as E. coli and Klebsiella spp., respectively. Contaminants were identified in 316 (16.4%) of blood culture specimens.

TABLE I	Culture Isolates From Pediatric Bloodstream Infections (N=880)

The cumulative antimicrobial susceptibility data revealed high proportion of resistance in both E. coli and Klebsiella spp. to the most of the antibiotics tested (Table II). Amikacin, carbapenems, colistin and tigecycline had an antimicrobial efficacy of >70%. When compared with E. coli, the resistance rate in Klebsiella spp. was higher to most of the antibiotics; specifically, significant difference was observed with piperacillin, cefazolin, cefuroxime, ceftazidime, aztreonam, gentamicin, and colistin. However, the resistance rate to fluoroquinolones, doxycycline, cefoxitin, cefepime, and piperacillin/tazobactam were lower in Klebsiella spp. than E. coli among which the significant difference was only observed with cefoxitin.

TABLE II	In Vitro Activity of Antimicrobial Agents Against Pediatric Blood Culture Isolates of E. Coli and Klebsiella Spp.

Thirty-one isolates (24 K. pneumoniae and 7 E. coli) were not susceptible to ETP; among them, randomly selected 15 isolates (13 K. pneumoniae and 2 E. coli) were further tested. Nine were CRE and seven were CEG positive (5 of them had NDM, one of which also had KPC; further, one each were KPC and VIM; intriguingly, three of these isolates are not CRE). Further, among the nine CRE isolates, only four were CEG positive (3 NDM, and 1 NDM + KPC), and remaining five isolates may be resistant by other mechanisms not tested in this study. Interestingly, among the six non-CRE isolates, three were found positive for CEG (one each for NDM, KPC, and VIM).

Among these 15 cases, nine were successfully treated (2 were NDM, 1 was NDM + KPC and 1 was VIM positive; 5 were CEG negative), and three patients died (two were preterm with low birth weight, NDM positive; and third was full term with asphyxia/respiratory failure, CEG negative); and in remaining three, outcome could not be assessed. None of these 15 isolates was pan-drug resistant; notably, 13/15 (86.7%) isolates were susceptible to colistin and all of them were susceptible to tigecycline.

We documented significantly higher proportion of Klebsiella when compared with E. coli as the cause of BSI. The most effective antibiotic (E. coli and Klebsiella spp. combined) in the study was colistin (92.8%), followed by tigecycline (89.3%). Carbapenems (>77%) were sufficiently effective for the consideration of empirical therapy for Gram-negative bacterial sepsis [13]. Further, this report documents the emergence of CRE in pediatric wards in rural Southern India; also, substantiates that the presence of CEG need not confer clinical resistance to carbapenem. Thus, the testing of MIC is more important than the detection of CEG in terms of patient management [14].

Limitation of the study was that it was done at single center, which may not reflect the overall picture in India; however, it may be useful to forecast the prevalence of resistance in rural or similar resource-limited settings. Additionally, most patients were referred for blood culture only after the failure of empiric therapy, which might have prejudiced the high resistance rate observed in this study.

In conclusion, the present study documented the higher prevalence of Klebsiella spp. in pediatric BSI and emergence of CRE; this necessitates the strengthening of infection control measures and effective antibiotic policy to contain their spread in pediatric wards.

Acknowledgements: Dr. Padma Krishnan, University of Madras, and Dr. Sulagna Basu, National Institute of Cholera and Enteric Diseases, India for their kind contribution of control bacterial strains for the optimization of PCR.

Contributions: RS and S Srivani: Concept, study design, data analysis and manuscript preparation; MM: Designed the study, and provided critical inputs to manuscript; DS and SL: Acquisition of data, analysis and interpretation of data; S Saranya: Laboratory testing, data collection and documentation.

Funding: Partly supported by an ad-hoc research grant offered by Indian Council of Medical Research (grant number 5/3/3/21/2012-ECD-1); Competing interests: None stated.