Unusual accumulation of a wide array of antimicrobial resistance mechanisms in a patient with cytomegalovirus-associated hemophagocytic lymphohistiocytosis: a case report

• Published in: BMC infectious diseases Vol. 20; no. 1; p. 237
• Main Authors: Hasan, Mohammad Rubayet, Sundaram, Manu Somasundaram, Sundararaju, Sathyavathi, Tsui, Kin-Ming, Karim, Mohammed Yousuf, Roscoe, Diane, Imam, Omar, Janahi, Mohammad A, Thomas, Eva, Dobson, Simon, Tan, Rusung, Tang, Patrick, Lopez, Andres Perez
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20-03-2020; BioMed Central; BMC
• Subjects: Accumulation; Anemia; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotic resistance; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Antiviral agents; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Antiviral resistance; Bacteria; Bone marrow; Carbapenem-Resistant Enterobacteriaceae - drug effects; Carbapenem-Resistant Enterobacteriaceae - genetics; Care and treatment; Case Report; Case reports; Case studies; Child; Cidofovir; Colitis; Complications and side effects; Cytomegalovirus; Cytomegalovirus - drug effects; Cytomegalovirus - genetics; Cytomegalovirus - immunology; Cytomegalovirus infections; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - diagnosis; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - virology; Diagnosis; DNA sequencing; Drug resistance; Drug Resistance, Multiple, Bacterial - genetics; Drug Resistance, Multiple, Viral; E coli; Enzymes; Fatal Outcome; Fever; Ganciclovir; Ganciclovir - adverse effects; Ganciclovir - therapeutic use; Gene sequencing; Genes; Genomes; Genomics; Genotype; Hemophagocytic lymphohistiocytosis; Hemorrhage; Histiocytosis; Hospital admission and discharge; Hospitals; Humans; Infection; Infections; Infectious diseases; Inflammatory bowel disease; Laboratories; Lymphatic diseases; Lymphocytosis; Lymphohistiocytosis, Hemophagocytic - diagnosis; Lymphohistiocytosis, Hemophagocytic - drug therapy; Lymphohistiocytosis, Hemophagocytic - virology; Male; Metagenomics; Microbial drug resistance; Multidrug resistance; Multidrug resistant organisms; Multidrug-resistant organism; Mutation; Patients; Sepsis; Sepsis - drug therapy; Sepsis - microbiology; Sepsis - mortality; Ulcers; Valganciclovir; Vancomycin; Vancomycin-Resistant Enterococci - drug effects; Vancomycin-Resistant Enterococci - genetics; Virus diseases; Whole genome sequencing; Qatar; India; Cytomegalovirus; Hemophagocytic lymphohistiocytosis; Multidrug-resistant organism; Antiviral resistance
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-020-04966-z

Infections with multidrug-resistant organisms (MDRO) pose a serious threat to patients with dysregulated immunity such as in hemophagocytic lymphohistiocytosis (HLH), but such infections have rarely been comprehensively characterized. Here, we present a fatal case of HLH secondary to cytomegalovirus (CMV) infection complicated by both anti-viral drug resistance and sepsis from multiple MDROs including pandrug-resistant superbug bacteria.
A previously healthy, six-year-old boy presented with a 45-day history of fever prior to a diagnosis of hemophagocytic lymphohistiocytosis and hemorrhagic colitis, both associated with CMV. On hospital admission, the patient was found to be colonized with multiple, multidrug-resistant (MDR) bacteria including vancomycin-resistant enterococci (VRE) and carbapenamase-producing organisms (CPO). He eventually developed respiratory, urine and bloodstream infections with highly drug-resistant, including pandrug-resistant bacteria, which could not be controlled by antibiotic treatment. Antiviral therapy also failed to contain his CMV infection and the patient succumbed to overwhelming bacterial and viral infection. Whole genome sequencing (WGS) of the MDR bacteria and metagenomic analysis of his blood sample revealed an unusual accumulation of a wide range of antimicrobial resistance mechanisms in a single patient, including antiviral resistance to ganciclovir, and resistance mechanisms to all currently available antibiotics.
The case highlights both the risk of acquiring MDR superbugs and the severity of these infections in HLH patients.