Background:The choice of antimicrobial therapy for bloodstream infections is often empirical and based on the knowledge of local antimicrobial activity profiles of the most common bacteria causing such infections.Aims:The present study was aimed to investigate frequency of bacterial pathogens causing septicemia and their antimicrobial resistant pattern in hospital admitted patients.Settings and Design:It was a prospective study, conducted at Majeedia Hospital, Hamdard University, New Delhi, India.Material and Methods:We examined prospectively, 168 bacterial strains isolated from 186 clinically diagnosed septicemia cases admitted at a University Hospital in New Delhi, over a period of six months from July 2009 to December 2009. Antimicrobial susceptibility was performed according to Clinical and Laboratory Standards Institute (CLSI, USA) guidelines.Results:The most frequently identified Gram-positive bacteria were coagulase-negative staphylococci 63.5%, Staphylococcus aureus 23.1%, enterococci 5.8% and alpha-haemolytic streptococci 5.8%. The most frequently Gram-negative bacteria identified were Acinetobacter species 31%, Salmonella typhi 24.1%, Escherichia coli 23.3% and Pseudomonas aeruginosa 13.8%. Coagulase-negative staphylococci showed maximum resistance to cefaclor 57.1% and ampicillin 46.9%. Staphylococcus aureus showed maximum resistance to amoxicillin 100% and ampicillin 91.7%. Acinetobacter species showed maximum resistance to amoxicillin 89.7%, amoxiclav 87.1% and ampicillin 85.7%. Salmonella typhi, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae showed maximum resistance to ampicillin, 46.4%, 92%, 93.8% and 100%, respectively.Conclusions:Gram-negative pathogens predominated in bloodstream infections. Resistance to most of the antimicrobial agents for a number of pathogens implicated in bloodstream infections, especially in Gram-negative bacteria, has reached worrisome levels and continues to increase.

Fourteen strains of S. Typhi (n=13) and S. Paratyphi A (n=1) resistant to ciprofloxacin were compared with 30 ciprofloxacin decreased-susceptibility strains on the basis of qnr plasmid analysis, and nucleotide substitutions at gyrA, gyrB, parC and parE. In ciprofloxacin-resistant strains, five S. Typhi and a single S. Paratyphi A showed triple mutations in gyrA (Ser83-->Phe, Asp87-->Asn, Glu133-->Gly) and a novel mutation outside the quinolone resistance determining region (QRDR) (Met52-->Leu). Novel mutations were also discovered in an isolate (minimum inhibitory concentration 8 microg/ml) in gyrA gene Asp76-->Asn and outside the QRDR Leu44-->Ile. Out of 30 isolates with reduced susceptibility, single mutation was found in 12 strains only. Genes encoding qnr plasmid (qnr A, qnr B, AAC1-F) were not detected in ciprofloxacin-resistant or decreased-susceptibility strains. Antimicrobial surveillance coupled with molecular analysis of fluoroquinolone resistance is warranted for reconfirming novel and established molecular patterns of resistance, which is quintessential for reappraisal of enteric fever therapeutics.

The therapeutic alternatives available for use against ciprofloxacin-resistant enteric fever isolates in an endemic area are limited. The antibiotics currently available are the quinolones, thirdgeneration cephalosporins and conventional first-line drugs. In this study, the MICs of various newer drugs were determined for 31 ciprofloxacin-resistant enteric fever isolates (26 Salmonella enterica serovar Typhi and 5 S. enterica serovar Paratyphi A). MICs for ciprofloxacin, ofloxacin, gatifloxacin, levofloxacin, cefotaxime, cefixime, cefepime and azithromycin were determined using Etest strips and the agar dilution method. By Etest, all of the ciprofloxacin-resistant isolates had ciprofloxacin MICs ¢32 mg ml with the other quinolones (92-100 %) in S. Typhi. The rise in MIC levels of these antimicrobials is a matter for serious concern.

Antimicrobial resistance in Salmonella spp. is of grave concern, more so in quinolone-resistant and extended-spectrum b-lactamase (ESBL)-producing isolates that cause complicated infections. The MIC of azithromycin, ciprofloxacin, cefixime, cefepime, ceftriaxone, gatifloxacin, imipenem, levofloxacin, meropenem and ofloxacin (E-test strip) and tigecycline and faropenem (agar dilution) against 210 Salmonella spp. was determined. MIC 90 (defined as the antimicrobial concentration that inhibited growth of 90 % of the strains) of the carbapenems (imipenem and meropenem) for Salmonella Typhi and Salmonella Paratyphi A was 0.064 mg ml "1 . MIC 90 of faropenem was 0.25 mg ml "1 for S. Typhi, S. Paratyphi A and Salmonella Typhimurium. The MIC 90 of azithromycin for all Salmonella spp. ranged from 8 to 16 mg ml "1. Tigecycline showed an MIC 90 of 2 mg ml "1 for S. Typhi, 1 mg ml "1 for S. Paratyphi A and 4 mg ml "1 for S.Typhimurium. We concluded that tigecycline and the carbapenems are likely to have roles in the final stage of treatment of quinolone-resistant and ESBL-producing multidrug-resistant salmonellae.

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