42 years old male presented with
(ABG): revealed type 1 respiratory failure
Scrub typhus, a life-threatening zoonotic bacterial infection caused by Orientia tsutsugamushi and transmitted by trombiculid mite larvae, is a public health challenge that extends beyond the so-called Tsutsugamushi Triangle, the region where this infection has traditionally been endemic in Asia and Northern Australia. A billion people are estimated to be at risk in endemic regions, with an estimated 1 million cases and 150,000 deaths annually. Scrub typhus typically presents as an acute febrile illness that may be associated with headache, cough, shortness of breath, and altered sensorium. An eschar at the site of the mite bite serves as a highly distinctive diagnostic clue. When this infection is untreated, the median case fatality is approximately 6% but can reach 70% in severe disease. Severe disease (including multiorgan dysfunction and shock) develops in approximately one third of hospitalized patients and can lead to death in approximately a quarter of cases despite therapy.
Historically, scrub typhus has been treated with doxycycline or chloramphenicol. However, data from sufficiently powered, randomized, controlled trials are lacking, particularly for severe scrub typhus. In recent years, chloramphenicol has been used less frequently because of its toxicity profile, and oral azithromycin is increasingly used for mild scrub typhus. A small, prospective, open-label, randomized trial in South Korea involving patients with mild scrub typhus showed that single-dose azithromycin (500 mg) was as effective as doxycycline (200 mg) daily for a week.
Intravenous Treatment for Scrub Typhus (INTREST) clinical trial was conducted to compare the efficacy and safety of three 7- day intravenous antibiotic treatments (doxycycline, azithromycin, or a combination of both) in patients with severe scrub typhus and concluded that combination therapy with intravenous doxycycline and azithromycin was superior to monotherapy with either drug with respect to the primary composite outcome of death at day 28, persistent complications at day 7, and persistent fever at day 5 in both the modified intention-to-treat and per-protocol populations. The superiority of combination therapy was mainly due to a reduced incidence of persistent complications at day 7, when the frequencies of respiratory, renal, hepatic, and central nervous system complications were lower in the combination- therapy group than in either of the monotherapy groups.
Severe scrub typhus is associated with substantial complications and death. Common manifestations resulting in organ involvement include acute respiratory distress syndrome, hepatitis, shock, meningoencephalitis, and renal failure.
Why a combination of doxycycline and azithromycin should be more clinically effective in the treatment of severe scrub typhus than either of the drugs alone is a matter of speculation. Through different mechanisms, the two drugs inhibit messenger RNA translation at the bacterial ribosome. Azithromycin binds the 23SrRNA of the 50S ribosomal subunit at the polypeptide exit tunnel, and doxycycline prevents aminoacyl-tRNA binding to the 30S ribosomal subunit. The combination of the two drugs may result in a more complete blockade of protein synthesis with a consequently greater effect against O. Tsutsugamushi. Better bacterial control during the critical first week of infection may result in prevention and faster resolution of severe manifestations of illness.
This case highlights the importance of early recognition and aggressive management of scrub typhus, particularly in patients presenting with severe complications like ARDS and thrombocytopenia. The patient responded well to the combination of azithromycin and doxycycline, coupled with intensive supportive care. There is some clinical support for the use of dual therapy in severe cases of scrub typhus. Dual therapy offers significant advantages over monotherapy, particularly in high-risk or critically ill patients.
Dr Ramapriya Critical Care Kauvery Hospital, Chennai
Mentor:
Dr Vetriselvan P Associate Consultant Critical Care Medicine Kauvery Hospital, Chennai
