Comparison of azithromycin vs doxycycline prophylaxis in leptospirosis, A randomized double blind placebo-controlled trial

Abstract

Introduction: Leptospirosis is an important zoonotic disease in paddy field with 29.5% prevalence rate in Mazandaran province and 4% to 52% mortality rate among hospitalized patients. Prevention is an important strategy for the control of this disease. This study aimed to compare the prophylactic effect of azithromycin versus doxycycline against leptospirosis in an endemic area in north of Iran.
 Methodology: In this randomized double-blind placebo-controlled trial, paddy field workers (n = 187) were randomized to receive azithromycin (500mg weekly), doxycycline (200 mg weekly) or placebo starting one week before exposure to paddy field, during and to four weeks after. Paddy field workers aged 18- 65 years who signed the informed consent form were assessed for signs and symptoms of leptospirosis in addition to serologic evidence of the disease 6th and 12th week. Data were analyzed with SPSS version 13 using Chi-square and Fisher exact test and ANOVA.
 Results: From June to September 2016, 187 participants were entered the study to receive azithromycin (n = 66), doxycycline (n = 71) or placebo (n = 50). In terms of preventing against clinical leptospirosis, there was not any significant difference between three arms, though there was statistically significant difference of seropositivity after 6 and 12 weeks in comparison to baseline among all three groups (P = 0.029) and between active treatment (eg. azithromycin and doxycycline) groups and placebo group (P = 0.01).
 Conclusion: Azithromycin like doxycycline decreased seropositivity without significant effect on clinical leptospirosis.

Current Evidence on the Antimicrobial Treatment and Chemoprophylaxis of Human Leptospirosis: A Meta-Analysis

“…Eight trials assessed prophylactic treatment against leptospirosis with different strategies: four of them with 200 mg of doxycycline weekly [ 24 , 26 , 28 , 30 ], two with daily oral penicillin [ 23 , 27 ], another two with a single dose of doxycycline at the time of exposure to flood water [ 25 , 29 ]. One of them also compared doxycycline prophylaxis with a weekly azithromycin regimen [ 30 ]. Among all these trials, they comprise 4905 patients.…”

“…There was enormous heterogeneity among the studies. Two of them showed a clear benefit of doxycycline [ 24 , 28 ], but the most recent trial result did not show this benefit [ 30 ]. However, this study showed a lower percentage of new IgG seropositivity in those patients who received chemoprophylaxis than in the placebo group ( Table 3 ) [ 30 ].…”

“…Two of them showed a clear benefit of doxycycline [ 24 , 28 ], but the most recent trial result did not show this benefit [ 30 ]. However, this study showed a lower percentage of new IgG seropositivity in those patients who received chemoprophylaxis than in the placebo group ( Table 3 ) [ 30 ]. The administration of a single dose of doxycycline at times of exposure reached statistical significance that favors doxycycline (OR 0.23; 95% CI 0.07–0.77; p = 0.02) ( Figure 6 ).…”

“…However, in most studies, there seems to be a tendency to have fewer cases of leptospirosis in the groups with chemoprophylaxis regimens. Only the Alikhani study [ 30 ] shows more cases of clinical leptospirosis in the doxycycline chemoprophylaxis group than in the control group. Nevertheless, in this study, there are fewer cases of new IgG seropositivity patients in the doxycycline group.…”

Acute Kidney Injury and Acute Liver Failure in Leptospira Infection and Weil’s Syndrome

“…Prolonged elevation in serum bilirubin levels may not adequately reflect recovery of liver injury in this disease. ICG clearance appears to be a promising marker for the detection of hepatic dysfunction and recovery in icteric leptospirosis (66).…”