Conditioning without Antibiotic Prophylaxis May Not Increase Infection Related Mortality in Allogeneic Hematopoeitic Stem Cell Transplantation

Background: Hematopoeitic stem cell transplantation (HSCT) is the standard of care in a large number of disorders for over three decades all over the world. Despite significant improvements in conditioning protocols, the mortality still remains significantly high and peri-transplant infections continue to be a big challenge. A number of regimens for primary prophylaxis against various infections are being used during conditioning with varying success in reducing the incidence of infections. But it might result in increasing incidence of resistant infections besides increasing the transplant cost.

Objectives: To evaluate the impact of infection prophylaxis upon infection related mortality in allo-HSCT.

Materials and Methods: We analyzed the data of 96 consecutive stem cell transplants performed in our centre between 1998 and 2006. We did not use any prophylaxis for bacterial or fungal infections in these cases. A total of 86 patients underwent HSCT for various indications at our 3 bedded bone marrow transplantation unit (BMTU). The mean age was 24 years (range: 2–45). The indications for allogeneic transplants were CML: 28, AML: 8, ALL: 5, CLL: 1, MDS: 1, Thalassemia major: 12, PRCA: 1 and Aplastic/Fanconi’s anemia: 4. The indications for autologous transplants included multiple myeloma (15), NHL (8), AML(7) and solid tumors (5) Allogeneic transplants were performed with full HLA matched siblings. The conditioning was done with standard Busulfan-Cyclophosphamide (Bu-Cy) based protocols for leukemia; Fludarabine, Cyclophosphamide & ATG for PRCA and aplastic anemia and Bu-Cy-ATG for thalassemia. The median cell dose was 6.8 × 10⁸ (range: 2.7–11.7) MNC/Kg. The median day of engraftment (ANC > 500/mm³) was day 10 (range 7–20). None of the patients received primary prophylaxis with any antibiotics or antifungal agents during conditioning. Patients who developed neutropenic fever or the evidence of bacterial or fungal infections were treated with empirical therapy based on our hospital infection policy based antimicrobial protocols.

Results: A total of 64 patients developed documented infections. Amongst these the positive bacteriological cultures were obtained from blood (64%) followed by urine (12%), sputum (8%) and catheter related infections (5%) The antibiotics were changed if specific organism could be identified. Antifungal agents were started empirically if fever continued 48 hours after initiation of initial antibiotics even if no causative agent was identified. 78 (92 %) patients required antibiotics. Total 38 patients had documented bacterial infections. The majority of bacterial infections (56%) occurred in the first 30 days following SCT. The organisms identified were mainly Gram negative bacteria (77% e.g, E Coli-68%, Pseudomonas aeroginosa-13%, Enterobacter-2%, Klebsiella pneumoniae-2%) with a few gram positive organisms (23%). The gram positive organisms were Staphylococcus aureus (13%) and Coagulase negative staphylococcus (8%). 05 patients developed septicemia with fatal multi-organ failure. The 100 day mortality due to infections has been 9 (9.2 %) and one year infection related mortality was 13%. This rate of infections was not significantly higher as compared to he rates when antibiotics & antifungals were used as prophylaxis Fungal infections were documented in 19 patients(Candida: 57%, Aspergillus: 33% and Zygomycetes: 10%)

Conclusion: The study demonstrates that adherence to a well planned infection control strategy for transplant units and strict preventive measures can ensure a low incidence of infections with success rates comparable to any developed country. Although the number is small to make any definite conclusion, there is a feasibility of avoiding prophylactic use of antibiotics in conditioning regimens, thereby, decreasing the risk of resistant infections besides bringing down the cost of transplant procedure which has a great bearing on the availability of transplant to all eligible patients in a country like India where affordability is restricted greatly by cost factors.