Infections Are a Major Cause of Prolongation of Hospital Stay in Hematopoietic Stem Cell Transplants in Tropical, Developing Countries: Profile of a Transplant Center in North India

Introduction: There are evidence based guidelines for the prophylaxis and management of infections in hematopoietic stem cell transplant recipients. However, the infection profile of transplant centers differs from center to center even in different regions of the same country. The reported incidence of bacterial, fungal and viral infections ranges widely from 13-60%, 4-30% and 2-16% respectively across the world. Here we report the infection profile in our transplant center.

Methods: This was a retrospective study done at a tertiary care referral center in India. Data of hematopoietic stem cell transplants from 2004 –2014 was analyzed. All recipients received trimethoprim-sulphamethoxazole, levofloxacin, fluconazole and acyclovir prophylaxis. Voriconazole was used in allogeneic transplants after 2011. Definite bacterial infections were defined as any positive cultures from blood, urine, sputum, pus. Definite infective diarrhea was defined as stool culture or Clostridium difficile toxin positivity. Definite fungal infection required confirmation by culture or histopathology. Probable fungal infection required one each of host factors, clinical features and mycological evidence. Possible fungal infection required any one of the above three factors. Antifungals were started on day 3-5 as per the febrile neutropenia guidelines. CMV was monitored by RQ-PCR weekly till 100 days post transplant. All recipients were nursed in HEPA (high efficiency particulate air) filtered rooms till the resolution of infection or engraftment whichever was later.

Results: Data of first 100 (36 allogeneic and 64 autologous) transplants was analyzed. All patients except 3 developed fever requiring antibiotics. There were 68 documented bacterial infections in 47 transplant recipients (47%). Gram negative were the most frequent isolates 49/68 (72.1%) followed by Gram positive organisms 19/68 (27.9%). Polymicrobial infections were seen in 11 patients (16.1%). Infections were significantly more common in allogeneic (26/36) than autologous transplant recipients (34/64) (p=0.005). Diarrhea was seen in 59 patients. Clostridium difficile toxin positivity was seen in 7 cases (11.8%).

CMV infection was seen in 9 allogeneic HSCT recipients (25%). All patients had ongoing GVHD at the time of CMV reactivation and were on additional immunosuppression with corticosteroids. The diagnosis of fungal infection was made in 54 patients (54%). It was categorized as probable in 10 and possible in 44. Definite fungal infections could not be documented in any case. Antifungals were used for a median duration of 4.5 days (SD ±6.9).

Infection attributed mortality was 9%. The median duration of antimicrobial usage was 13 days (SD±9.2). The median duration of total hospital stay was 38 days (SD±31.7). The median day of neutrophil engraftment was 12 days (SD±3.5). Multiple regression analysis revealed duration of antimicrobial use to be associated with hospital stay (p<0.0001).

Conclusions: Antimicrobials were used for up to one third of the total hospital stay of HSCT. Bacterial and fungal infections were the major cause for prolongation of the hospital stay in our center. The incidence of possible fungal infections is higher than centers in other parts of the world and signifies the need for alternative detection methods to confirm the diagnosis. Whether the agent, host or environment factor in tropical and developing countries, contributes to this increased risk of infections needs to be evaluated in a prospective study.