Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis.
BACKGROUND
Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO)-associated bacteremia.


METHODS
This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012. It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR) and MDRO-associated bacteremia.


RESULTS
Out of 75 bacteremias, 42.7% were gram-positive (GP), and 57.3% were gram-negative (GN). GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias). Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms) and Klebsiella pneumoniae(13.3% of total, 23.3% of GN organisms) were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS) bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p < 0.05).


CONCLUSIONS
Our findings have major implications for the management of febrile neutropenia, especially in breakthrough bacteremia and fever when patients are already on broadspectrum antibiotics. Emergence of resistance to 3GCs and, to a lesser extent, to carbapenems in GN isolates has to be considered seriously in our local guidelines for empiric treatment of febrile neutropenia, especially given that their occurrence was proven to be associated with poorer outcomes.
Department of Internal Medicine, Makassed General Hospital Beirut, Lebanon.
Rima
R
Moghnieh
Department of Internal Medicine, Makassed General Hospital Beirut, Lebanon.
Nour
N
Estaitieh
Division of Hematology-Oncology, Department of Internal Medicine, Makassed General Hospital Beirut, Lebanon.
Anas
A
Mugharbil
Department of Laboratory Medicine, Makassed General Hospital Beirut, Lebanon.
Tamima
T
Jisr
Pharmacy Department, Makassed General Hospital Beirut, Lebanon.
Dania I
DI
Abdallah
Faculty of Public Health, Lebanese University Beirut, Lebanon.
Fouad
F
Ziade
Research Coordinator, Makassed General Hospital Beirut, Lebanon.
Loubna
L
Sinno
Division of Hematology-Oncology, Department of Internal Medicine, Makassed General Hospital Beirut, Lebanon.
Ahmad
A
Ibrahim
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology* / Q000382:microbiology; D002511:Cephalosporins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D064147:Febrile Neutropenia / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology / Q000382:microbiology; D006801:Humans; D007861:Lebanon / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D011379:Prognosis; D012189:Retrospective Studies; D055815:Young Adult
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002511:Cephalosporins
3GCR gram-negative bacteria; Lebanon; MDR gram-negative bacteria; bacteremia; febrile neutropenia