Uppuluri et al recently reported a single center experience with management of pediatric acute myeloid leukemia (AML) and impact of infectious complications over a two-decade period.[1] This is a highly informative study and allows inference of chronological trends in etiology of infectious complications and mortality in pediatric AML across India. It is commendable to note that despite an increase in the prevalence of multidrug resistant (MDR) organisms, early infection-related mortality of less than 10% was achieved. We highlight three other pertinent conclusions that must be drawn from this study and have wider implications.

The finding of?Klebsiella pneumoniae?as the most common Gram-negative pathogen is in line with several other Indian studies on AML.[2] Alarmingly, the incidence of MDR bacteremia in Indian data continues to increase, with one study noting carbapenem resistance in 60% and colistin resistance in 80% of isolates.[3] An increasing trend in MDR Gram-negative infections after 2012 is echoed in the same study, rising from 0?fore 2012 to over 20% in 2017. This has shown exponential rise in the use of colistin, tigecycline, and carbapenems. Despite a rise in MDR infections, the new antibiotic pipeline (including agents in all phases of development) as of 2019 has been found to be similar to the one in 2013 and 2015, indicating an unavoidable lag between emergence of resistant isolates and identification of newer agents.[4]

This trend is foreseen to cause greater challenges in the coming few years, and must be mitigated with steps taken today. First, implementation of antibiotic stewardship programs has been shown to reduce broad-spectrum antibiotic usage in the absence of clinical or microbiologic indications and must be implemented where possible. For instance, pharmacy guidelines that prevent the use of carbapenems without definite indications potentially reduce unnecessary antibiotic usage. The use of stool surveillance, as used by the authors, allows risk-adapted initiation of carbapenems/colistin/tigecycline in appropriate patients and has reduced unnecessary antibiotic usage. Neutropenic patients with AML usually need to be started on broad-spectrum antibiotics agents in the absence of microbiologic proof. Active antibiotic deescalation in AML, guided by microbiology reports, allows a reduction in broad-spectrum antibiotic usage without affecting clinical outcomes and must be followed wherever possible.[5]

Fungal infections constitute the next biggest threat to patients with acute leukemia. Posaconazole provides effective antimold activity and is the agent of choice for most patients with AML. The authors report low rates of proven fungal infections, with the use of micafungin for all patients. Micafungin has demonstrated reduced rates of prophylaxis failure in patients with AML, but it is associated with a similar incidence of invasive fungal infections and a higher incidence of infections with uncommon species like?Mucoralres.[6] Several problems associated with posaconazole such as drug interactions, variable absorption, and peak drug levels are overcome with micafungin, and a decision to switch must be taken based on individual data.

It is again impressive to note that the induction mortality despite high rates of MDR infections has largely stayed around the 10% mark. Cognizant use of broad-spectrum antibiotics, directed by clinical and microbiologic indications, is essential to prevent the emergence of an MDR Gram-negative pandemic in the coming years.

Conflict of Interest

None declared.

Author Contributions

• References

  • 1?Uppuluri R, Swaminathan V, Ravichandran N. et al.?Chemotherapy for childhood acute myeloid leukemia and associated infections over two decades in India: Timeline and impact on outcome. Indian J Med Paediatr Oncol 2020; 41 (06) 869-873
  • 2?Jain H, Rengaraj K, Sharma V. et al.?Infection prevalence in adolescents and adults with acute myeloid leukemia treated in an Indian tertiary care center. JCO Glob Oncol 2020; 6 (06) 1684-1695
  • 3?Kumar H, Mehra N, Ganesan P. et al.?Patterns of infection and mortality associated with intensive AML induction therapy: 10 year experience from a tertiary cancer centre in India. Blood 2018; 132 (Suppl. 01) 4008
  • 4?Butler MS, Paterson DL.?Antibiotics in the clinical pipeline in October 2019. J Antibiot (Tokyo) 2020; 73 (06) 329-364
  • 5?Fuller R, Moshier E, Jacobs SE. et al.?Practicing antimicrobial stewardship: de-escalating antibiotics in patients with acute myeloid leukemia and neutropenic fever. Open Forum Infect Dis 2020; 7 (05) a138
  • 6?Epstein DJ, Seo SK, Huang Y-T. et al.?Micafungin versus posaconazole prophylaxis in acute leukemia or myelodysplastic syndrome: a randomized study. J Infect 2018; 77 (03) 227-234