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MANAGEMENT OF INFECTIOUS COMPLICATIONS IN PATIENTS WITH
ACUTE LEUKAEMIA
Ph.D. Lutfulla Saydullayevich Makhmonov
Head of the Department of Hematology,
Samarkand State Medical University
Khudoyor Makhmudovich Shomirzaev
Head of the Blood Transfusion Unit,
Samarkand Regional Multidisciplinary Medical Centre
Zukhriddin Ziyadullaevich Muyiddinov
Haematologist, Haematology Centre,
Samarkand Regional Multidisciplinary Medical Centre
Dilafruz Abdikhalimovna Amerova
Assistant teachet of the Department of Hematology,
Samarkand State Medical University
Abstract
. Infectious complications are among the most frequent and life-threatening
challenges in the treatment of acute leukaemia, particularly during periods of chemotherapy-
induced neutropenia. This study aimed to evaluate the incidence, spectrum, and outcomes of
infections in patients with acute leukaemia treated at the Samarkand Regional
Multidisciplinary Medical Centre between 2019 and 2023. A total of 108 patients with acute
myeloid or lymphoblastic leukaemia were analysed. Febrile episodes occurred in nearly 90%
of patients, with 61% of infections microbiologically confirmed. Gram-negative bacteria
were the predominant pathogens, with
E. coli
,
K. pneumoniae
, and
P. aeruginosa
being the
most common; a significant proportion exhibited multidrug resistance. Fungal infections and
viral reactivations were also observed, particularly in those with prolonged neutropenia. The
infection-related mortality rate was 17.6%, largely due to sepsis caused by resistant Gram-
negative organisms. Early initiation of empirical antibiotic therapy and G-CSF support were
associated with improved survival. The findings underscore the urgent need for improved
diagnostics, targeted antimicrobial therapy, and local infection control strategies to reduce
mortality in acute leukaemia patients in resource-limited settings.
Keywords:
Acute leukaemia, infectious complications, febrile neutropenia, multidrug
resistance, Gram-negative bacteria, fungal infections, sepsis, chemotherapy, Uzbekistan.
Introduction
Acute leukaemia, encompassing both acute myeloid leukaemia (AML) and acute
lymphoblastic leukaemia (ALL), is a rapidly progressing malignancy of the bone marrow
and blood, characterised by the uncontrolled proliferation of immature myeloid or lymphoid
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cells. Intensive induction and consolidation chemotherapy are essential to achieve remission
and long-term disease control; however, these regimens result in profound myelosuppression,
leading to significant immunosuppression and, consequently, a high vulnerability to
infectious complications.
Infectious complications represent one of the most frequent and life-threatening challenges
in the management of acute leukaemia. Despite advancements in supportive care and the
availability of broad-spectrum antimicrobial agents, infections remain a leading cause of
morbidity and mortality in this patient population. This is especially true during periods of
chemotherapy-induced neutropenia, when innate immune defences are critically impaired.
Even brief delays in initiating appropriate antimicrobial therapy in febrile neutropenic
patients can lead to rapid clinical deterioration, septic shock, and death.
The immunocompromised state in acute leukaemia is further aggravated by mucosal barrier
injury due to cytotoxic agents, central venous catheter use, prolonged hospitalisation,
parenteral nutrition, and frequent transfusions. These factors contribute to the translocation
of endogenous flora and facilitate colonisation and invasion by nosocomial and multidrug-
resistant (MDR) pathogens. In many centres, including those in developing countries,
infections are increasingly caused by organisms resistant to conventional antibiotics, such as
extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, methicillin-
resistant Staphylococcus aureus (MRSA), and carbapenem-resistant Gram-negative bacilli.
Invasive fungal infections (IFIs) constitute another major complication, particularly in
patients with prolonged neutropenia, corticosteroid use, or relapsed/refractory disease.
Aspergillus spp., Candida spp., and Mucorales are among the most common fungal
pathogens. These infections are often difficult to diagnose early due to non-specific
symptoms and limited access to advanced diagnostics such as galactomannan and β-D-
glucan assays or high-resolution CT imaging. As a result, empirical antifungal therapy is
often initiated based on clinical suspicion, but this approach may delay targeted therapy or
lead to overtreatment.
Viral infections, especially reactivation of latent herpesviruses such as HSV and CMV, are
also of concern in acute leukaemia patients undergoing immunosuppressive therapy or
haematopoietic stem cell transplantation. These infections may manifest as mucositis,
pneumonitis, or retinitis and can further complicate the already complex clinical picture.
Effective management of these infectious complications requires a multifaceted approach:
risk stratification, timely empirical antibiotic administration, de-escalation based on
microbiological data, prophylactic antimicrobial strategies, and stringent infection control
measures. Moreover, regular surveillance of local resistance patterns and infection trends is
essential to guide empirical therapy and inform antimicrobial stewardship programs.
In Uzbekistan, while access to chemotherapy and basic supportive care for haematologic
malignancies has improved, there remains a significant gap in infection prevention and
management infrastructure. Regional data on pathogen prevalence, resistance profiles,
clinical outcomes, and post-infectious complications are sparse. Without such information,
local protocols remain heavily reliant on international guidelines, which may not fully
reflect regional microbial ecology, healthcare resources, or patient populations.
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Therefore, the present study aims to investigate the clinical characteristics, microbiological
spectrum, antimicrobial resistance patterns, treatment responses, and outcomes of infectious
complications in patients with acute leukaemia treated at the Samarkand Regional
Multidisciplinary Medical Centre. By identifying key risk factors and evaluating the
effectiveness of current management strategies, the study seeks to contribute to the
development of evidence-based, locally relevant infection control protocols. Ultimately, the
goal is to reduce infection-related mortality and optimise the clinical management of acute
leukaemia in resource-constrained environments.
Results
This study analysed 108 patients diagnosed with acute leukaemia who developed infectious
complications during chemotherapy between 2019 and 2023. The cohort included 68
patients with acute myeloid leukaemia (AML) and 40 with acute lymphoblastic leukaemia
(ALL), with a median age of 39 years (range 15–72), and a male-to-female ratio of 1.4:1. All
patients received intensive induction or consolidation chemotherapy, resulting in significant
and prolonged neutropenia, with the median absolute neutrophil count (ANC) dropping
below 500 cells/mm³ for an average duration of 10.4 ± 3.7 days. During this neutropenic
period, 97 patients (89.8%) experienced at least one febrile episode, and 112 infectious
episodes in total were recorded among them, as some had multiple infections during their
treatment course.
Microbiologically documented infections accounted for 61% of cases, while 29% were
clinically diagnosed without culture confirmation, and 10% remained febrile neutropenia of
unknown origin despite empirical treatment. Among microbiologically confirmed infections,
Gram-negative bacteria were the predominant pathogens, accounting for 55.8% of isolates.
The most common organisms included
Escherichia coli
(21.5%),
Klebsiella pneumoniae
(18.7%), and
Pseudomonas aeruginosa
(12.4%). Notably, 39.4% of Gram-negative isolates
were extended-spectrum beta-lactamase (ESBL)-producing, and 16.9% exhibited
carbapenem resistance. Gram-positive bacteria accounted for 24.1% of isolates, with
Staphylococcus epidermidis
and
Enterococcus faecalis
being the most frequently identified.
Fungal infections were diagnosed in 14 patients (13%), mostly invasive pulmonary
aspergillosis and disseminated candidiasis. Viral reactivations, primarily HSV and CMV,
were observed in 8 cases, confirmed by PCR assays or clinical presentation.
Empirical antibiotic therapy was initiated in all febrile neutropenic patients, most commonly
with piperacillin-tazobactam or cefepime. Escalation to carbapenems was required in 38.6%
of cases, especially in patients with MDR organism risk factors or hemodynamic instability.
Vancomycin was added in 29 patients due to suspected Gram-positive infections. Antifungal
therapy was introduced empirically in 42 patients and targeted in 14, using voriconazole,
fluconazole, or amphotericin B depending on clinical suspicion and drug availability. G-CSF
was administered to 63.8% of patients to support neutrophil recovery. The median time to
defervescence was 4.3 ± 2.1 days. Targeted therapy based on culture and sensitivity
improved outcomes in 82.6% of cases with confirmed pathogens.
The infection-related mortality rate was 17.6% (19 patients), with sepsis due to MDR Gram-
negative infections being the leading cause of death. These cases were often associated with
delayed culture results, resistance to multiple antibiotics, and the absence of early intensive
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care support. Among patients who survived, the average hospital stay was 21.8 ± 6.4 days. A
statistically significant association was found between infection-related mortality and
prolonged neutropenia (>10 days), presence of MDR pathogens, and delayed initiation of
empirical therapy (p < 0.05 for all). Conversely, early initiation of empirical antibiotics
within 1 hour of fever onset, combined with G-CSF support and appropriate escalation, was
associated with a higher survival rate.
These findings underscore the high burden of infectious complications in patients with acute
leukaemia, particularly from multidrug-resistant Gram-negative pathogens. Despite
established empirical treatment protocols, infection-related mortality remains significant,
especially in patients with severe neutropenia and delayed microbiological guidance. The
data highlight the urgent need for enhanced diagnostic capabilities, access to rapid pathogen
identification tools, and regional antimicrobial stewardship efforts to improve outcomes in
this high-risk patient population.
Discussion
The results of this study highlight the persistent and severe threat posed by infectious
complications in patients undergoing treatment for acute leukaemia. Despite advances in
chemotherapy and supportive care, infections remain a leading cause of morbidity and
mortality, particularly during prolonged periods of neutropenia induced by intensive
induction or consolidation regimens. The high frequency of febrile episodes (89.8%) and
documented infections in over half of the patients underscores the vulnerability of this
population and the central role infection management plays in determining treatment
outcomes.
Gram-negative bacteria emerged as the dominant group of pathogens, consistent with global
epidemiological trends. The predominance of
E. coli
,
Klebsiella pneumoniae
, and
Pseudomonas aeruginosa
aligns with findings from international haematology centres, but
the high proportion of multidrug-resistant (MDR) strains—particularly ESBL-producing and
carbapenem-resistant isolates—is concerning. These resistant organisms significantly reduce
the efficacy of first-line empirical regimens and necessitate early escalation to carbapenems
or combination therapies. The association between MDR infections and higher mortality in
this cohort reflects the urgent need for proactive infection surveillance and the rational use
of broad-spectrum antibiotics to prevent further resistance development.
Fungal infections, although less frequent, were associated with increased length of hospital
stay and higher treatment complexity. Most were due to
Aspergillus
species or disseminated
Candida
, occurring in patients with prolonged neutropenia and previous antibiotic use. The
limited availability of fungal biomarkers and imaging studies in our setting may have
resulted in underdiagnosis or delayed detection. Nonetheless, empirical antifungal therapy in
persistent febrile neutropenia was a life-saving measure in many cases, emphasising the
importance of early clinical suspicion and access to antifungal drugs like voriconazole and
amphotericin B.
Viral reactivations, particularly of HSV and CMV, though relatively infrequent, added
another layer of complexity to patient management. These findings suggest the need for
enhanced virological monitoring, especially in patients receiving immunosuppressive
therapy or presenting with mucocutaneous lesions, and the routine availability of PCR-based
assays for early detection and preemptive treatment.
The infection-related mortality rate of 17.6% is in line with data from comparable centres in
middle-income countries. Most deaths were attributable to sepsis caused by resistant Gram-
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negative organisms, typically in patients who experienced prolonged neutropenia, delayed
empirical antibiotic administration, or lacked early access to intensive care. Importantly,
timely initiation of empirical therapy within the first hour of fever onset, along with
granulocyte-colony stimulating factor (G-CSF) support and close clinical monitoring, was
associated with improved survival. These observations reinforce global recommendations on
the “golden hour” principle in febrile neutropenia and support the inclusion of rapid-
response pathways in institutional protocols.
Our findings underscore the need to develop and implement comprehensive infection
prevention and control strategies tailored to the local microbial environment. These should
include regular antibiogram updates, standardised empirical therapy guidelines, rigorous
hand hygiene and catheter care protocols, and educational programs for healthcare providers.
Additionally, building diagnostic capacity—particularly for rapid microbial detection,
resistance profiling, and fungal biomarkers—is essential to optimise antimicrobial
stewardship and reduce unnecessary drug exposure.
This study also reveals several resource limitations that constrain infection management in
our setting. Delays in microbiological diagnosis, limited access to newer antimicrobial
agents, and inconsistent availability of diagnostic imaging hinder timely intervention.
Moreover, many patients lacked consistent prophylaxis due to supply interruptions or
financial barriers. Addressing these systemic gaps requires not only medical interventions
but also institutional investment and health policy support.
In conclusion, infectious complications in acute leukaemia remain a significant threat to
patient survival, especially in resource-constrained settings. Multidrug-resistant Gram-
negative infections and delayed intervention are the principal drivers of infection-related
mortality. Strengthening early diagnostic capabilities, ensuring timely empirical treatment,
enhancing infection control practices, and updating local treatment protocols are critical to
improving outcomes. The insights from this study can serve as a foundation for regional and
national policy development aimed at reducing infection-related mortality in haematological
malignancies.
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