carbapenem resistant gram - negative bacteria ( gnb ) such as enterobacteriaceae ( cre ) ( including escherichia coli [ crec ] and klebsiella pneumoniae [ crkp ] ) , pseudomonas aeruginosa ( crpa ) and acinetobacter baumanni ( crab ) are important emerging causes of nosocomial blood stream infections and carry significant mortality . urgent threat  by the us centers for disease control and prevention ( cdc ) , while the antimicrobial availability task force formed by the infectious diseases society of america had identified crpa and crab of particular importance , because of growing antimicrobial resistance among these isolates and shrinking therapeutic options . indian single center studies overall report a prevalence of carbapenem resistance in up to 12 - 15% of enterobacteriaceae and 40 - 60% in a. baumanii and p. aeruginosa . however , there is little data from india about the clinical profile and treatment outcome of infections caused by these organisms . this was a retrospective study performed at a 600 bed tertiary care facility in chennai , india between may 2011 and may 2012 . we identified all blood culture results that had yielded a growth of carbapenem - resistant gnb during the study period . blood cultures were performed using bact / alert ( biomerieux ) culture system , and species ' identification was carried out with vitek - gni card ( biomerieux ) . antibiotic susceptibility was performed using disc diffusion interpretive criteria as per revised clinical and laboratory standards institute performance standards . gram - negative bacteremia was defined as the isolation of gram - negative bacilli in blood culture specimen in at least two bottles of two different culture sets with clinical features compatible with systemic inflammatory response syndrome . clinical parameters analyzed included severity of illness as calculated by acute physiology and chronic health evaluation ( apache ) ii score on the day of bacteremia onset , presumed source of infection and presence of arterial and venous central catheters or hemodialysis catheters . the source of bacteremia was defined on the basis clinical and microbiologic evaluation using infections criteria proposed by cdc . presence of risk factors such diabetes , recent surgery , organ transplant and immunosuppression were recorded . prior antibiotic usage , dose of colistin and requirement for renal replacement therapy ( rrt ) after treatment with colistin commenced were also noted . the records of 50 patients with bacteremia caused by crec , crkp , crab , crpa were identified and analyzed . the mean age of patients was 52.3 years and 32 ( 64% ) were male . the most common co - morbid condition was diabetes mellitus ( 30% ) , followed by chronic kidney disease ( 22% ) . the total mean duration of hospitalization was 24.68 days with a mean of 11.76 days of intensive care unit ( icu ) care . the mean time to onset of bacteremia was 6.4 days after admission . of the 50 patients , 96% had already received antibiotics , including beta - lactam / beta - lactamase inhibitors ( 32% ) and carbapenems ( 40% ) [ table 1 ] . the mean (  standard deviation [ sd ] ) apache ii score at the onset of bacteremia was 19.64  3.8 . thirty - eight percent ( n = 19 ) patients had septic shock complicating bacteremia . fourteen episodes ( 28% ) of bacteremia were attributed to ventilator - associated pneumonia ( vap ) , 12 episodes ( 24% ) to the central line related bloodstream infections ( clabsi ) , 10 episodes ( 20% ) were due to intra - abdominal infections ( iai ) and 9 episodes ( 18% ) to urinary tract infections . the most common causative organism in our study was crkp ( 44% ) followed by crec ( 26% ) , while crab and crpa were isolated in 20% and 10% patients respectively [ table 2 ] . observed outcome of patients all patients received a loading dose of colistin with a mean of 5.14 million units intravenously followed by a mean 5.18 million units total daily dose . mean creatinine clearance ( calculated estimated glomerular filtration rate [ egfr ] ) at the initiation of colistin was 52.48 ml / min . six patients ( 12% ) required rrt after initiation of colistin for worsening renal functions ; all recovered to normal renal function . the overall survival at 30 days was 40% in our study with lowest survival rates for clabsi ( 33.3% ) , with survival rates for vap , iai and urosepsis patients of 35.7% , 40% and 44.4% respectively . overall 30 days survival for crab and crkp bacteraemia were lowest ( 30% and 31.8% respectively ) , while survival rates for crpa and crec bacteraemia were 40% and 61.5% respectively . we also found that patients treated with combination therapy had lower mortality ( 44.8% ) compared with colistin monotherapy ( 66.6% ) although this was statistically not significant ( p = 0.35 ) [ table 3 ] . carbapenem resistance in gram - negative organisms is increasingly encountered in healthcare - associated infections in india . bacteremic episodes due to these organisms carry a high mortality as shown by previous studies from other countries . in our study , the most common carbapenem resistant gram - negative isolate was crkp ( 44% ) followed by crec ( 26% ) with more than half of all episodes due to pneumonia or clabsi , similar to two previous indian studies presented as abstracts in scientific meetings . our patients had a high apache ii score ( 19.64  3.8 sd ) and had a mean icu stay of 11.76 days , with a mean time of onset of bacteremia after admission of 6.4 days . these results are in concordance with previous studies implicating these organisms as causes of healthcare - associated infections . seriously ill - patients in icus for prolonged periods often require central lines , dialysis catheters , broad spectrum antibiotics , and mechanical ventilation , which make them susceptible to resistant hospital - acquired infections . notably only 40% of our patients had received carbapenems , but virtually all had antibiotic exposure , suggesting that healthcare exposure and overall prior antibiotic exposure may be more important risk factors for developing carbapenem resistant infections rather than prior receipt of carbapenems . colistin has emerged as the cornerstone of therapy for carbapenem - resistant gnb , but the correct dose and frequency of dosing is a subject of on - going study . the mean colistin loading dose in our study was only 5.14 million units followed by mean total daily dose of 5.18 million units intravenously , even with a mean egfr of 52.48 ml / min at colistin initiation . use of low colistin doses may be because of a perceived concern about nephrotoxicity ; our study period was also prior to evolution of new colistin dosing recommendations . in our study , six patients ( 12% ) required new onset rrt due to worsening renal functions after colistin initiation but this was fully reversible with dosing adjustments , which was reassuring and similar to other studies . the overall 30 days survival rate in our cohort was only 40% , but it was difficult to assess whether this was due to sepsis itself or due to underlying severe illness and multiple co - morbidities . mortality in our patients was highest when clabsi or vap was the source of bacteremia and when crab and crkp were the causative organisms . better survival rates from the west have been reported , but similar results to ours have been observed in two previous indian abstract presentations . higher colistin doses are associated with higher microbiologic clearance and reduced mortality at 7 days although 28 days mortality did not differ . it is also possible that relatively low dose our patients received may have contributed to mortality . we also observed that patients treated with two drug combinations had a trend towards a higher survival rate than those treated with colistin monotherapy , as observed in other studies also . small study numbers in the two groups and the fact that more severely ill patients may receive combination treatment , may have resulted in the absence of a statistically significant difference . we acknowledge significant limitations in our study : its retrospective nature , relatively small sample size and absence of a control group for comparison . we have shown that carbapenem - resistant gram - negative bacteremia is a serious healthcare - associated infection in critically ill - patients in indian icus with co - morbidities and prior antibiotic exposure ; k. pneumoniae is the most common organism at our center . thirty days survival rate is only 40% and even lower for clabsi or vap or when due to a. baumanii or k. pneumoniae . colistin is the cornerstone of therapy and may need to be studied at higher doses to optimize the outcome ; nephrotoxicity requiring rrt was seen in 12% of patients only and was reversible in all . combinations of other antibiotics with colistin may result in a lower mortality compared with monothrapy , however this needs needs to be explored through a randomized controlled study
background : growing antimicrobial resistance and limited therapeutic options to treat carbapenem - resistant bacteremia prompted us to evaluate the clinical outcomes associated with healthcare - associated bacteremia.methods:this was a retrospective observational study of carbapenem - resistant gram - negative bacteremia performed at a tertiary care facility in chennai , india between may 2011 and may 2012.results:in our study , patients had mean 11.76 days of intensive care unit ( icu ) care and mean time to onset of bacteremia was 6.4 days after admission . 
 the commonest organism was klebsiella pneumoniae ( 44% ) . 
 patients with combination treatment had lower mortality ( 44.8% ) compared with colistin monotherapy ( 66.6% ) ; ( p = 0.35).conclusion : carbapenem resistant bacteremia is a late onset infection in patients with antibiotic exposure in the icu and carries a 30 days mortality of 60% ; k. pneumoniae is the most common organism at our center . 
 two drug combinations appear to carry a lower mortality compared with monotherapy .