Effectiveness of treatment regimens for Typhoid fever in the nalidixic acid-resistant S. typhi (NARST) era in South India

Abstract

The epidemiology of typhoid fever in South Asia has changed. Multi-drug resistant (MDR) Salmonella typhi ( S. typhi) is now frequently resistant to nalidixic acid and thus labelled NARST. Treatment failure with the use of fluoroquinolones has been widely noted, forcing clinicians to adopt alternative treatment strategies. In this observational study, we looked at various treatment regimens and correlated clinical and microbiological outcomes. In 146 hospitalised adults, the median minimum inhibitory concentration (MIC) for ciprofloxacin was 0.38 µg/mL with a median fever clearance time (FCT) of eight days (range = 2-35 days). Of the regimens used, gatifloxacin and azithromycin had a shorter FCT of six days compared to ceftriaxone (ten days; P < 0.001). Though mortality and relapse in our cohort was low, NARST seemed to correlate with mortality ( P = 0.006). Gatifloxacin or azithromycin clearly emerge as the drugs of choice for treatment of typhoid in South India.

Response of extensively drug resistant Salmonella Typhi to treatment with meropenem and azithromycin, in Pakistan

“…No evidence is available to establish fever clearance time for XDR typhoid. Data from previous studies for MDR typhoid and fluoroquinolone resistant strains, has shown that defervescence is achieved in less than 7 days [11][12][13][14]. These results are in line with the expected time to defervescence for non-resistant typhoid fever which is 3.5-8 days from initiation of antimicrobial therapy [15,16].…”

The Invisible Burden: Diagnosing and Combatting Typhoid Fever in Asia and Africa

“…Typhi isolates that demonstrated MDR has declined in recent years [9]. With rapid defervescence following the use of these newer-generation antimicrobials [10], the number of severe typhoid cases that required hospitalization also decreased. More recently, sentinel hospitals in India have been reporting fewer cases of typhoid; therefore, there has been a widespread perception that typhoid is no longer a problem [11].…”

Case report of infective spondylodiscitis due to nalidixic acid-resistant Salmonella paratyphi A

“…Nalidixic acid resistance is greater than 75% and 60% for S. typhi and S. paratyphi , respectively, in India and is associated with mortality. [ 1 21 ] Our decision to start combination therapy was shaped by various factors including drug-resistant pathogen, vertebral involvement and clinical failure with azithromycin.…”

“…Typhoidal Salmonella ( Salmonella enterica serovars Typhi and Paratyphi A, B, C) are gram-negative bacilli that usually present as undifferentiated febrile illness. [ 1 ] Salmonella osteoarticular infections are common in sickle cell anaemia and immunocompromised hosts. [ 2 3 4 ] However, Salmonella osteomyelitis has also been reported in immunocompetent individuals.…”