treatment of urinary-tract infections associated with extended-spectrum beta-lactamase. in a separate study, cre were treated with colistin, amikacin, and tigecycline, and emphasizes the importance of using gentamicin in patients undergoing chemotherapy or stem-cell therapy procedures. while colistin had shown promising activity against carbapenemase-producing isolates, more recent data suggest a resistance to it is already emerging and it will soon become ineffective. using another antibiotic concomitantly with carbapenem can help prevent the development of carbapenem resistance. one specific study showed a higher rate of carbapenem resistance when using meropenem alone compared with combination therapy with moxifloxacin. in addition, several drugs were tested to gauge their effectiveness against cre infections. in vitro studies have shown that rifampin has synergistic activity against carbapenem-resistant e. coli and k. pneumoniae. however, more data are needed to determine if rifampin is effective in a clinical setting. several new agents are in development. the main areas where scientists are focusing is new β-lactamase inhibitors with activity against carbapenemases. some of these include mk-7655, nxl104, and 6-alkylidenepenam sulfones. the exact way they affect the carbapenemases is unknown. another experimental agent with activity against cre is eravacycline. epidemiology prior to 1992, cre were relatively uncommon in the u.s. according to data from the national nosocomial infection service, between 1986 and 1990, only 2.3% of 1825 enterobacteriaceae isolates sampled were found to be resistant. according to the u.s. centers for disease control, cre producing what was the most common type of carbapenem-destroying enzyme in 2001 were first detected in a north carolina hospital in 1996. since then, they have been identified in health care facilities in 41 other states. in 2012, 3% of patients in chicago-area icus carried cre. the same data indicated a 30% colonization rate in long-term care facilities (e.g. nursing homes), where patients are not symptomatic. during just the first half of 2012, almost 200 hospitals and long-term acute care facilities treated at least one patient infected with these bacteria. cre have become increasingly common in the us. the meropenem yearly susceptibility test information collection program noted that resistance within k. pneumoniae alone increased from 0.6% in 2004 to 5.6% in 2008. the first outbreak involving colistin-resistant, carbapenem-resistant k. pneumoniae (crkp) in the u.s. was discovered in detroit, michigan in 2009, involving three different healthcare institutions. in an active surveillance study in seven u.s. states over two years, the crude overall incidence of cre was 2.93 per 100,000 population. georgia and maryland had a significantly higher than predicted incidence adjusted for age and race. increases in cre have not been limited to the us. by 2011, cre was reported in at least 22 countries. between 2009 and 2012, 10 cases of cre infections were documented in icu patients in a melbourne, australia, hospital. some cases of cre are associated with receipt of medical care in the us. strains found in israel had genetic similarity to strains from the us. hospital handwashing stations were found to be environmental reservoirs for cre after screening all wet-area locations, including sinks, water fountains, and ice machines. the main reservoirs for cre were the icu sinks, and inappropriate cleaning methods accounted for transmission from sink to sink. the cre strains in the sinks and the strains infecting the icu patients were identical per genetic analysis. at-risk patients were being infected in the hospital setting. mortality cre resistance depends upon a number of factors such as the health of the patient, whether the patient has recently undergone a transplant, risk of co-infection, and use of multiple antibiotics. carbapenem minimal inhibitory concentrations (mics) results may be more predictive of clinical patient outcomes than the current categorical classification of the mics being listed as susceptible, intermediate, or resistant. the study aimed to define an all-cause hospital mortality breakpoint for carbapenem mics that were adjusted for risk factors. another objective was to determine if a similar breakpoint existed for indirect outcomes, such as the time to death and length of stay after infection for survivors. seventy-one patients were included, of which 52 patients survived and 19 patients died. classification and regression tree analysis determined a split of organism mic between 2 and 4 mg/liter and predicted differences in mortality (16.1% for 2 mg/liter versus 76.9% for 4 mg/liter). in logistic regression controlling for confounders, each imipenem mic doubling dilution doubled the probability of death. this classification scheme correctly predicted 82.6% of cases. patients were accordingly stratified to mics of ≤2 mg/liter (58 patients) and ≥4 mg/liter (13 patients). patients in the group with a mic of ≥4 mg/liter tended to be more ill. secondary outcomes were also similar between groups. patients with organisms that had an mic of ≥4 mg/liter had worse outcomes than those with isolates of an mic of ≤2 mg/liter. at new york presbyterian hospital, part of columbia university medical center in new york, ny, a study was conducted on the significant rise in carbapenem resistance in k. pneumoniae from 1999 to 2007. following a positive blood culture from a patient, overall mortality was 23% in 7 days, 42% in 30 days, and 60% by the end of hospitalization. the overall in-hospital mortality rate was 48%. at soroka medical center, an israeli university teaching hospital, a study was done between october 2005 and october 2008 to determine the direct mortality rate associated with carbapenem-resistant k. pneumoniae bloodstream infections. the crude mortality rate for those with the resistant bacteremia was 71.9%, and the attributable mortality rate was determined to be 50% with a 95% confidence interval. the crude mortality rate for control subjects was 21.9%. as a result of the study, soroka medical center started an intensive program designed to prevent the spread of carbapenem-resistant k. pneumoniae. a 2013 retrospective study at the shaare zedek medical center of patients with urinary tract infections (bacteriuria) caused by carbapenem-resistant klebsiella pneumoniae (crkp) showed no statistically significant difference in mortality rates from patients with bacteriuria caused by carbapenem-susceptible k. pneumoniae (cskp). a 29% mortality rate was seen in patients with crkp infection compared to a 25% mortality rate in patients with cskp infections that produced extended-spectrum beta-lactamase (esbl). both mortality rates were considerably higher than that of patients with drug-susceptible urosepsis. most patients in the study had other illnesses, including dementia, immune compromise, kidney failure, or diabetes mellitus. the main risk factor for death found by the study was being bedridden, which significantly increased the chance of death. this suggests that the deaths were due to reasons other than bacteriuria. total length of hospitalization was somewhat longer in patients with crkp infections (28 ± 33 days compared to 22 ± 28 days for patients with cskp infection). in a case-control study of 99 patients compared with 99 controls at mount sinai hospital (manhattan), a 1,171 bed tertiary care teaching hospital, 38% of patients in long-term care that were affected by cre died from k. pneumoniae infection. patients had risk factors including diabetes, hiv infection, heart disease, liver disease, chronic kidney disease, one was a transplant recipient. 72% of patients who were released from the hospital with cre were readmitted within 90 days. a 2008 study at mount sinai identified outcomes associated with carbapenem-resistant klebsiella pneumoniae infections, in which patients in need of organ or stem cell transplants, mechanical ventilation, prolonged hospitalization, or prior treatment with carbapenems, had an increased probability of infection with carbapenem-resistant k. pneumoniae. a combination of antibiotics worked to treat infection and survival rates of infected patients increased when the focus of infection was removed. cre infections can set in about 12 days after liver transplantation, and 18% of those patients died a year after transplantation in a 2012 study. public health implications bacterial survival on surfaces studies have found prolonged viability of bacteria on stainless-steel surfaces at room temperature. in a specific study, stainless steel was inoculated with 107 cfu/cm2 e. coli and k. pneumonia, containing blactx-m-15 and blandm-1 (antibiotic-resistant genes) respectively. thirty days later (at room temperature, 22˚ c), 104 viable cells remained; and, after 100 days, 100 cfu/cm2 of e. coli remained. in contrast, on copper and copper alloy surfaces, rapid death of antibiotic-resistant bacterial strains, as well as destruction of plasmid and genomic dna, can be observed. studies suggest that exposure to dry copper surfaces inhibits the respiration and growth of producers by releasing copper ions. increased horizontal gene transfer (hgt) is observed simultaneously with cell viability on stainless steel surfaces. hgt is one of the major factors responsible for creating antibiotic resistance in bacteria. this suggests that immediate decontamination of surfaces is important in preventing the spread of antibiotic resistance genes. it has also been shown that horizontal transfer of antibiotic-resistant β-lactamase genes does not occur on antimicrobial copper surfaces. as copper surfaces degrade naked dna (and plasmid dna in antibiotic-resistant e. coli and k. pneumonia), copper surfaces would halt hgt. horizontal gene transfer has been demonstrated to occur readily on dry surfaces such as stainless steel, but not on copper and copper alloy surfaces. the rate of bacterial death increased proportionally with the percentage of copper in the copper alloy surface. this can be very important in future clinical and community settings, as an increase in copper utilization in hospital room equipment could help to greatly reduce the spread of antibiotic-resistant infection and the horizontal gene transfer of this antibiotic resistance.