Septicemia in Chemotherapy Induced Neutropenic Acute Myeloid Leukemia (AML) Inpatients and Outpatients: A 5 Year Retrospective Experience.
Authors: Halim Timotheus Y. , Lavoie Julye C. , Barnett Micheal J. , Forest Donna L. , Hogge Donna E. , Nantel Stephen H. , Nevill Thomas J. , Shepherd John D. , Song Kevin W. , Sutherland Heather J. , Toze Cynthia L. , Smith Clay A. 
Published: April 2020

Patients (pts) with AML undergoing curative intent chemotherapy (CTX) are highly susceptible for septicemia due to profound and prolonged neutropenia, in conjunction with damage to the gastrointestinal mucosa, and the use of vascular access devices. Despite aggressive empiric antimicrobial therapy, and the use of prophylactic antibiotics, septicemia remains a major cause of morbidity in this group. Over the past decade the spectrum of pathogens that cause infections in neutropenic pts has changed, with gram+ve microorganisms replacing gram-ve bacilli.

In order to identify the incidence, and cause of septicemia and the resistance pattern of bacteria in AML pts treated with curative intent CTX in the Leukemia/BMT program of BC, all positive blood cultures collected between Feb, 1999 and Feb, 2004 were evaluated retrospectively.

623 separate CTX cycles administered to 295 patients were reviewed (m=157, f=138). Median age at diagnosis was 52y (17–76). CTX regimen were classified as 7+3 or similar (conventional dose cytarabine + anthracycline) (group 1), or as high dose cytarabine containing regimen (with or without anthracycline) (group 2). 328 cycles were given as induction intend-CTX, while 295 where given as consolidation. 426 cycles were spend entirely as inpatients (IP) (from administration of CTX to ANC&gt;0.5); 40 cycles were spend as early discharge (ED) (from CTX administration to discharge as outpatient prior to d+15 or ANC&gt;0.5); 157 cycles were spend entirely as outpatients (OP). 126 episodes of septicemia were recorded in 623 cycles of CTX (20%), of which 21 episodes yielded more than 1 identified organism. Percent occurrence of septicemia stratified by CTX protocol indicated 17% (57/332) for group 1, and 24% (69/291) for group 2 (p&lt;0.05). When stratified by CTX sequence, we note a difference in septicemia incidence between induction-intent CTX 17% (55/328), and consolidation CTX 24% (71/295) (p&lt;0.05). Percent positive blood cultures per cycle discharge status were 25% for IP, 33% for ED, and 17% for OP (p&lt;0.05). A total of 152 isolates were found, grouped as 53% gram +ve, 40% gram-ve, 3% unknown, and 4% fungal. The dominant organisms were coagulase negative Staphylococcus (22%), Viridans Streptococcus (18%), E.coli (11%), Klebsiella sp. (8%), and Staphylococcus aureus (4%). E.coli displayed resistance to ampicillin in 44%, and resistance to ciprofloxacin in 27% of isolates (all ciproRE.coli were also ampR). In addition 2 MRSA were isolated, and no vancomycin resistance was encountered in any isolates.142 pts died since diagnosis, while 153 are alive with a follow-up of 729d median (range 5d-1827d). The cause of death was relapse or refractory AML in 78% (110/142), treatment related mortality (TRM) post BMT in 13% (19/142), TRM post CTX in 7% (10/142). Of the 10 pts who died of post chemo TRM, only 1 died as a direct result of septicemia.

Septicemia remains a frequent complication in high-risk neutropenic AML pts. Supported by our results, we have constructed an infectious risk stratification scheme pertaining to the CTX treatment of AML in IP, OP and ED settings. Furthermore, we report that while infections in this population constitutes a significant source of morbidity, mortality directly attibutable to septicemia is rare with prompt intervention.