Treatment
Several reports have indicated the global spread of Typhi and Paratyphi strains resistant to all first-line antibiotics—ampicillin, chloramphenicol, and co-trimoxazole—collectively known as multidrug-resistant (MDR) Salmonella [14]. All MDR Typhi and Paratyphi carry the IncHI1 plasmid [15], though more recently in has been found that their prevelance in India is declining and being replaced by the emergence and spread of QRDR Salmonella strains resistant [16] to fluoroquinolones that has been acquired through chromosomal mutations in the quinolone resistance gene qnrS and/or the quinolone resistance determining region (QRDR) harboring gyrB, parE, gyrA, and parC genes [17], with the later 2 being the most common mutations here. Resistance to third-generation cephalosporins is associated with the acquisition of several extended-spectrum β-lactamase (ESBL) genes. The XDR H58 S. Typhi strain, resistant to ampicillin, chloramphenicol, co-trimoxazole, fluoroquinolones, and third-generation cephalosporins, was first identified in Pakistan in 2016 [18]. Azithromycin and carbapenems are last resort antibiotics for treating Salmonella infections, but there have been reports of S. Typhi strains developing resistance to azithromycin and invasive non-typhoidal Salmonella (NTS) becoming resistant to carbapenems [19] [20]. Given India’s position as locus for the transmission of XDR H58 S [22] and the clinical picture the decision was made to empirically treat the patient with ceftriaxone.
HLH remains a very rare but potentially fatal complication of enteric fever with atleast 53 cases being reported in the literature [22]. Though our patient only had a 3-5% probability or 119 points on the Hscore [23] at the height of his illness, a high a high index of suspicious is required given the unexplained neurological symptoms [24], low local availability of drugs like etoposide and tests like sCD25 levels. The MRI findings only had the effect of heightening our suspicions. The hyperintensity in the splenium of the corpus callosum, known as the boomerang sign [25], is a documented cytotoxic lesions of the corpus callosum [26]. Whereas the T2 shine through ( a hyperintesity on DWI and T2 with true restriction of diffusion as confirmed on ADC) is typically indicative of vasogenic edema [27]. Given the excessive release of pro-inflammatory cytokines [28] in HLH it may be a plausible radiologic manifestation. While further work-up for the disease and an empiric dose of dexamethasone was recommended by hematology, but given the rapid improvement thereafter it was withdrawn.
Other complications one must remain vigilant for include include gastrointestinal hemorrhage, acute kidney injury, myocarditis, pneumonia, anemia, disseminated intravascular coagulation, encephalopathy, cholecystitis, intestinal perforation, and hepatitis [29].