Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

Role of Neutrophil Gelatinase-associated Lipocalin (NGAL) and Other Clinical Parameters as Predictors of Bacterial Sepsis in Patients Presenting to the Emergency Department with Fever.

Background: Bacterial sepsis is associated with significant morbidity and mortality. However, to date, there is no single test that predicts sepsis with reproducible results. We proposed that using a combination of clinical and laboratory parameters and a novel biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL) may aid in early diagnosis. Method: A prospective cohort study was conducted at a tertiary care center in South India (June 2017 to April 2018) on patients with acute febrile episodes fulfilling the Systemic Inflammatory Response Syndrome (SIRS) criteria. Plasma NGAL and standard clinical and laboratory parameters were collected at the admission. Bacterial sepsis was diagnosed based on blood culture positivity or clinical diagnosis. Clinically relevant plasma NGAL cut-off values were identified using the receive operating characteristic (ROC) curve. Clinically relevant clinical parameters along with plasma NGAL's risk ratios estimated from the multivariable Poisson regression model were rounded and used as weights to create a new scoring tool. Results: Of 100 patients enrolled, 37 had bacterial sepsis. The optimal plasma NGAL cut-off value to predict sepsis was 570 ng/mL [area under the curve (AUC): 0.69]. The NGAL sepsis screening tool consists of the following clinical parameter: diabetes mellitus, the presence of rigors, quick sequential organ failure assessment (qSOFA) >2, a clear focus of infection, and the plasma NGAL >570 ng/mL. A score of <3 ruled out bacterial sepsis and a score >7 were highly suggestive of bacterial sepsis with an interval likelihood ratio (LR) of 7.77. Conclusion: The NGAL sepsis screening tool with a score >7 can be used in the emergency department (ED) to identify bacterial sepsis. How to cite this article: Paul A, Newbigging NS, Lenin A, Gowri M, Varghese JS, Nell AJ, et al. Role of Neutrophil Gelatinase-associated Lipocalin (NGAL) and Other Clinical Parameters as Predictors of Bacterial Sepsis in Patients Presenting to the Emergency Department with Fever. Indian J Crit Care Med 2023;27(3):176-182.