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].