A total of 130 children (250 episodes of febrile neutropenia) were included in this study. Male to female ratio was 1.7: 1. Mean age at presentation was 6.5 years (range: 6 months -15 years, standard deviation: 4.29 years). Mean duration of fever was 72 hours (range: 2- 20 days, standard deviation: 3.09 days). Acute Lymphoblastic Leukaemia (ALL) was the most common malignancy noted at 186 episodes (74%), followed by Acute Myeloid Leukaemia (AML) at 47 episodes (19%) followed by Lymphoma, Ewing’s sarcoma and rhabdomyosarcoma. Respiratory symptoms (13%) were the most common presentation, followed by musculoskeletal symptoms (11%). Nine percent of the episodes had features of shock and were admitted to paediatric intensive care unit. No obvious focus of infection was noted in 57% episodes. During the course of hospitalization all the episodes had ANC <500; ANC<200 was observed in 50% of the episodes. The average number of cultures sent per episode of neutropenia was 1.536. A total of 384 cultures were sent, of which 92 (24%) were positive. Blood cultures constituted 246 of these of which 65 were positive. Once the blood cultures were sent, empiric antibiotics were started. In case of no clinical improvement/ worsening, further culture samples were taken under strict asepsis. A total of 92 urine culture, 26 endotracheal trap aspirate cultures and 20 cerebrospinal fluid cultures were obtained. Most common organisms isolated were gram negative bacteria (48 isolates, 52.2%), followed by gram positive cocci (33 isolates, 35.8%), fungi (6 isolates, 6.5%) and 5 polymicrobial cultures (5.5%) in 92 culture positive episodes. [Figure 1] Amongst the gram negative bacteria, the lactose fermenters (29 isolates, 31.5%) predominated with Escherichia coli being the most common (19 isolates, 20.6%) followed by Klebsiella (10 isolates, 10.8%). Non fermenting gram negative bacteria constituted 19 isolates, (20.6%) including Pseudomonas (6 isolates, 6.5%). Amongst gram positive coagulase negative staphylococcus (CONS) was the most common (29%), followed by Streptococcus and Enterococcus.
The sensitivity patterns have been displayed in tables. [Table 1, 2] We noticed that almost all gram positive isolates in our cultures showed excellent response to first and second line antibiotics with CONS showing sensitivity of 96% to amikacin, 100% to ceftazidime, piperacillin-tazobactam, meropenem, vancomycin and colistin. Streptococci and Enterococci had less susceptibility to first line antibiotics but responded well to vancomycin and meropenem. The gram negative bacteria on the other hand had poor response to ceftazidime and relatively better response to amikacin. Lactose fermenting bacteria like Escherichia coli had sensitivity to ceftazidime in only 36% and NFGNB was sensitive in 25%. Escherichia coli strain was sensitive to amikacin in 71 % episodes and Pseudomonas had excellent susceptibility (100%) as well. Klebsiella and NFGNB (other than Pseudomonas) had relatively poor sensitivity to amikacin. All gram negative bacteria both lactose-fermenters and non-fermenters showed a mean sensitivity of only 16.7, 24.7 and 33.7 to piperacillin-tazobactom, ceftazidime and meropenem respectively.. NFGNB (other than Pseudomonas) and Klebsiella were 44% sensitive to amikacin. Pseudomonas and Escherichia coli had a sensitivity of 100% and 71% respectively to amikacin. The mean of sensitivity of all gram negative bacteria to amikacin was 57. NFGNB (other than Pseudomonas) had a sensitivity of 68% to colistin. Escherichia coli and Klebsiella showed even higher sensitivity of 90%, 80% respectively to colistin.
First line antibiotics (ceftazidime and amikacin) were started for all the episodes, however, 78 episodes required second line antibiotics. These 78 episodes comprised 47 positive cultures (out of 92 positive cultures) and 12 deaths (out of 13 deaths). Of the 47 positive cultures within this group 31 belonged to gram negative group, while only 9 belonged to gram positive group. Episodes with gram negative isolates were more likely to require second line antibiotics (51%). [Table 3] Out of the 12 deaths in this group eight died due to gram negative bacteraemia. [Figure 2]
Pan drug resistance was found in 3 gram negative cultures, associated with 2 deaths. Extreme drug resistance was seen in 20 gram negative isolates, associated with 5 deaths. Multi drug resistance was seen in 13 gram negative isolates, associated with 1 death. Most drug resistance (i.e., MDR, XDR and PDR, a total of 36) was noticed in the gram negative group. [Table 4] Escherichia coli and Klebsiella were found to have more resistant isolates and highest mortality. [Figure 3]
Much higher mortality was seen in episodes with gram negative isolates and especially higher in drug resistant isolates. [Table 5] Amongst those requiring second line antibiotics, 12 deaths were reported of which eight deaths were due to gram negatives, one death was due to gram positive and two deaths due to fungal infection. In the group that required only first line antibiotic, most common isolate was gram positive bacteria (24 isolates) while gram negative bacteria relatively lesser (17 isolates). Only one death was reported in this group. There was only one death due to viral cause which was due to dengue haemorrhagic fever.