Vancomycin Resistant Enterococcus as a Leading Cause of Early Infection-Related Mortality in Older (≥ 60 Years) AML Patients Admitted to a Community Hospital for Standard Induction Chemotherapy.

Although generally accepted that age is a risk factor for chemotherapy-induced neutropenia and its complications, the relationship between patient age and the development of infectious complications following cytotoxic chemotherapy is unclear. Recent studies performed in elderly patients with NHL have shown advanced age to be an independent risk factor for prolonged myelosuppression, increased mucosal toxicity, and higher inpatient mortality during initial chemotherapy cycles. Little is known, however, if these findings can be extrapolated to elderly (> 60 yrs) patients with acute leukemia receiving induction chemotherapy. We studied the case records of all patients within this category (n=6) who received induction chemotherapy between the months of January 2005 to January 2006 to determine the type, frequency and severity of infections that occurred within the first 30 days following treatment. Patients’ median age was 71 years (range 60–78), with male to female ratio of 1:1. All patients (100%) developed fever and mucosal toxicity during hospital course, with first febrile episode occurring an average of 9 days after chemotherapy (range 4–18 days), and lasting for an average duration of 5.4 days (range 2–7 days). Types of GI toxicity (stage II or higher) included: mucositis (100%), diarrhea (83%), neutropenic colitis (33%), bowel obstruction (16%), and GI bleed (16%), with initial mucosal symptoms DEVELOPING 2.5 days (median) after initial febrile episode. All febrile episodes (n=8) were associated with neutropenia (ANC < 500/mm³). An infectious etiology could be established in 7/8 episodes (88%), with the remainder (12%) defined as isolated fevers. Pulmonary infection (pneumonia) occurred most frequently in 50% of patients, followed by bacteremia (33%), neutopenic enterocolitis (33%), and urinary tract infection (16%). 80% of patients had mixed infections involving > 1 site. Microbiologically, gram positive organisms were isolated most frequently (76%), with remaining isolates all non-bacterial in origin. Enterococcus faecium accounted for 90% of gram positive bacterial strains, with the remaining 10% due to Staphylococcus aureus. Of the enterococcal isolates, 78% were documented to be vancomycin- resistant (VRE). 3/6 patients (50%) died during the 30 day period following chemotherapy, with 2/3 patient deaths attributed to VRE sepsis. In both of these cases, VRE bacteremia was rapidly fatal; with a median time of 48 hrs elapsing between time of culture and time of death. These results suggest that elderly AML patients are at high risk for early mortality due to resistant gram positive bacterial infections such as VRE following induction chemotherapy. Antimicrobial regimens that include agents with coverage against these types of organisms such as linezolid or quinopristin-dalfopristin should be strongly considered when treating patients in this setting; especially when GI symptoms (mucositis, diarrhea) or symptoms of sepsis accompany fever episode.