rifampin and Scrub-Typhus

To explore the efficacy and safety of drugs in patients with scrub typhus.. For this systematic review and network meta-analysis, we searched PubMed, Embase, Web of Science, Cochrane Central Register of Clinical Trials, China National Knowledge Infrastructure (CNKI), and Wanfang data (WF) up to December 2021. All randomized controlled trials (RCTs) of antibiotics used to treat scrub typhus were included without language or date restrictions. The overall effectiveness was evaluated from 4 perspectives: cure rate (CR), defervescence time (DT), gastrointestinal symptoms-adverse events (GS-AD), and abnormal blood count-adverse events (ABC-AD). The quality of evidence was evaluated using the Cochrane Risk of Bias tool and GRADE system.. Sixteen studies involving 1,582 patients were included to evaluate 7 drugs, namely, azithromycin, doxycycline, chloramphenicol, tetracycline, rifampin, moxifloxacin, and telithromycin. In this network meta-analysis, rifampicin (82%) and chloramphenicol (65%) were more effective in terms of CR, and moxifloxacin (3%) from the quinolone family was the worst. Azithromycin caused the fewest events in terms of ABC-AD. No differences were found in this network meta-analysis (NMA) in terms of DT and GS-AD.. Rifampicin was associated with the highest CR benefit and the lowest risk of DT when used to treat patients with scrub typhus, except in areas where tuberculosis (TB) was endemic. Azithromycin was found to be better in CR and was associated with a lower probability of GS-AD and ABC-AD; therefore, it may be considered to treat pregnant women and children. Moxifloxacin had a much lower CR than other drugs and is, therefore, not recommended for the management of scrub typhus.. https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021287837.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Chloramphenicol; Female; Humans; Moxifloxacin; Network Meta-Analysis; Rifampin; Scrub Typhus

Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat scrub typhus include tetracyclines, chloramphenicol, macrolides, and rifampicin.. To assess and compare the effects of different antibiotic regimens for treatment of scrub typhus.. We searched the following databases up to 8 January 2018: the Cochrane Infectious Diseases Group specialized trials register; CENTRAL, in the Cochrane Library (2018, Issue 1); MEDLINE; Embase; LILACS; and the metaRegister of Controlled Trials (mRCT). We checked references and contacted study authors for additional data. We applied no language or date restrictions.. Randomized controlled trials (RCTs) or quasi-RCTs comparing antibiotic regimens in people with the diagnosis of scrub typhus based on clinical symptoms and compatible laboratory tests (excluding the Weil-Felix test).. For this update, two review authors re-extracted all data and assessed the certainty of evidence. We meta-analysed data to calculate risk ratios (RRs) for dichotomous outcomes when appropriate, and elsewhere tabulated data to facilitate narrative analysis.. We included six RCTs and one quasi-RCT with 548 participants; they took place in the Asia-Pacific region: Korea (three trials), Malaysia (one trial), and Thailand (three trials). Only one trial included children younger than 15 years (N = 57). We judged five trials to be at high risk of performance and detection bias owing to inadequate blinding. Trials were heterogenous in terms of dosing of interventions and outcome measures. Across trials, treatment failure rates were low.Two trials compared doxycycline to tetracycline. For treatment failure, the difference between doxycycline and tetracycline is uncertain (very low-certainty evidence). Doxycycline compared to tetracycline may make little or no difference in resolution of fever within 48 hours (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.90 to 1.44, 55 participants; one trial; low-certainty evidence) and in time to defervescence (116 participants; one trial; low-certainty evidence). We were unable to extract data for other outcomes.Three trials compared doxycycline versus macrolides. For most outcomes, including treatment failure, resolution of fever within 48 hours, time to defervescence, and serious adverse events, we are uncertain whether study results show a difference between doxycycline and macrolides (very low-certainty evidence). Macrolides compared to doxycycline may make little or no difference in the proportion of patients with resolution of fever within five days (RR 1.05, 95% CI 0.99 to 1.10; 185 participants; two trials; low-certainty evidence). Another trial compared azithromycin versus doxycycline or chloramphenicol in children, but we were not able to disaggregate date for the doxycycline/chloramphenicol group.One trial compared doxycycline versus rifampicin. For all outcomes, we are uncertain whether study results show a difference between doxycycline and rifampicin (very low-certainty evidence). Of note, this trial deviated from the protocol after three out of eight patients who had received doxycycline and rifampicin combination therapy experienced treatment failure.Across trials, mild gastrointestinal side effects appeared to be more common with doxycycline than with comparator drugs.. Tetracycline, doxycycline, azithromycin, and rifampicin are effective treatment options for scrub typhus and have resulted in few treatment failures. Chloramphenicol also remains a treatment option, but we could not include this among direct comparisons in this review.Most available evidence is of low or very low certainty. For specific outcomes, some low-certainty evidence suggests there may be little or no difference between tetracycline, doxycycline, and azithromycin as treatment options. Given very low-certainty evidence for rifampicin and the risk of inducing resistance in undiagnosed tuberculosis, clinicians should not regard this as a first-line treatment option. Clinicians could consider rifampicin as a second-line treatment option after exclusion of active tuberculosis.Further research should consist of additional adequately powered trials of doxycycline versus azithromycin or other macrolides, trials of other candidate antibiotics including rifampicin, and trials of treatments for severe scrub typhus. Researchers should standardize diagnostic techniques and reporting of clinical outcomes to allow robust comparisons.

Topics: Adult; Anti-Bacterial Agents; Azithromycin; Child, Preschool; Chloramphenicol; Doxycycline; Humans; Macrolides; Randomized Controlled Trials as Topic; Rifampin; Scrub Typhus; Tetracycline

Scrub typhus is a vector-borne disease caused by the pathogen Orientia tsutsugamushi. We review the published literature for evidence on drug treatment in scrub typhus. Doxycycline has a proven efficacy in several trials and a meta-analysis, although resistance has been documented in parts of northern Thailand. Macrolides are equally efficacious and have less adverse effects, but they are expensive. Azithromycin is the recommended drug in pregnancy and for children. Rifampicin is effective in areas where doxycycline resistance is present. Quinolones have shown some degree of efficacy but the evidence is scant. Most clinical evidence on drug treatment is from cases of mild-to-moderate scrub typhus. Further study is needed on the efficacy of different antibiotics in the treatment of severe, life-threatening scrub typhus.

Topics: Anti-Bacterial Agents; Azithromycin; Child; Clinical Trials as Topic; Doxycycline; Female; Humans; Macrolides; Orientia tsutsugamushi; Pregnancy; Rifampin; Scrub Typhus; Treatment Outcome

Doxycycline is currently the most frequently used treatment in patients with scrub typhus. However, doxycycline-resistant strains have been found, necessitating the development of a new treatment. Rifampin is known to be effective even for such strains. Our aim in this study was to compare the effects of rifampin and doxycycline treatment in patients with scrub typhus in areas in which resistance to doxycycline has not been reported.. Patients admitted to Chosun University Hospital and regional network hospitals between 2007 and 2009 with a body temperature ≥37.5°C and suspected to have scrub typhus were randomly assigned to 1 of 2 treatment groups: a group administered doxycycline 100 mg twice daily for 5 days and a group administered rifampin 600 mg once daily for 5 days. For treatment outcomes, fever, headache, muscle ache, and rash clearance times were compared between the groups.. The rifampin and doxycycline groups showed equivalence in all treatment outcomes evaluated. The proportions of patients with fever clearance within 48 hours were similar between groups. Furthermore, there was no significant difference in the occurrence of side effects following drug administration between groups.. On the basis of the finding that equivalent treatment effects and safety were found in patient groups that received 600 mg of rifampin and 200 mg of doxycycline, respectively, for 5 days to treat scrub typhus, rifampin may be considered an alternative treatment to doxycycline.. NCT00568711.

Topics: Aged; Anti-Bacterial Agents; Doxycycline; Exanthema; Female; Fever; Humans; Male; Middle Aged; Rifampin; Scrub Typhus; Treatment Outcome

Some strains of scrub typhus in northern Thailand are poorly responsive to standard antirickettsial drugs. We therefore did a masked, randomised trial to compare rifampicin with standard doxycycline therapy for patients with scrub typhus.. Adult patients with strictly defined, mild scrub typhus were initially randomly assigned 1 week of daily oral treatment with 200 mg doxycycline (n=40), 600 mg rifampicin (n=38), or doxycycline with rifampicin (n=11). During the first year of treatment, the combined regimen was withdrawn because of lack of efficacy and the regimen was replaced with 900 mg rifampicin (n=37). Treatment outcome was assessed by fever clearance time (the time for oral temperature to fall below 37.3 degrees C).. About 12,800 fever patients were screened during the 3-year study to recruit 126 patients with confirmed scrub typhus and no other infection, of whom 86 completed therapy. Eight individuals received the combined regimen that was discontinued after 1 year. The median duration of pyrexia was significantly shorter (p=0.01) in the 24 patients treated with 900 mg daily rifampicin (fever clearance time 22.5 h) and in the 26 patients who received 600 mg rifampicin (fever clearance time 27.5 h) than in the 28 patients given doxycycline monotherapy (fever clearance time 52 h). Fever resolved in a significantly higher proportion of patients within 48 h of starting rifampicin (900 mg=79% [19 of 24], 600 mg=77% [20 of 26]) than in patients treated with doxycycline (46% [13 of 28]; p=0.02). Severe gastrointestinal events warranted exclusion of two patients on doxycyline. There were two relapses after doxycycline therapy, but none after rifampicin therapy.. Rifampicin is more effective than doxycycline against scrub-typhus infections acquired in northern Thailand, where strains with reduced susceptibility to antibiotics can occur.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Doxycycline; Eosinophilia; Exanthema; Female; Fever; Follow-Up Studies; Gastrointestinal Diseases; Humans; Male; Middle Aged; Patient Dropouts; Rifampin; Scrub Typhus; Thailand; Time Factors; Treatment Outcome

Scrub typhus is an infectious disease caused by Orientia tsutsugamushi. The differences in virulence of O. tsutsugamushi prototypes in humans are still unknown. We investigated whether there are any differences in the clinical features of the Boryoung and Karp genotypes.. Patients infected with O. tsutsugamushi, as Boryoung and Karp clusters, who had visited 6 different hospitals in southwestern Korea were prospectively compared for clinical features, complications, laboratory parameters, and treatment responses. Infected patients in the Boryoung cluster had significantly more generalized weakness, eschars, skin rashes, conjunctival injection, high albumin levels, and greater ESR and fibrinogen levels compared to the Karp cluster. The treatment response to current antibiotics was significantly slower in the Karp cluster as compared to the Boryoung cluster.. The frequency of occurrence of eschars and rashes may depend on the genotype of O. tsutsugamushi.

Topics: Adult; Aged; Anti-Bacterial Agents; Doxycycline; Female; Genotype; Humans; Ketolides; Male; Middle Aged; Orientia tsutsugamushi; Prospective Studies; Republic of Korea; Rifampin; Scrub Typhus; Serotyping; Species Specificity; Treatment Outcome

In order to determine the effects of antibiotic treatment on the results of nested PCRs for scrub typhus, we investigated the frequency of positive outcomes at various times after antibiotic administration in patients with scrub typhus. The rate of detection by nested PCR with blood buffy coat before antibiotic administration was 90.5%. However, this decreased to 60.5% within 3 days after administration of antibiotics such as doxycycline and rifampin and to 10% by the fourth day following antibiotic administration. Since the sensitivity of nested PCR can be affected by antibiotic administration, clinicians should perform this PCR before antibiotic administration and at the latest within 3 days after antibiotic administration.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Blood; Doxycycline; Humans; Middle Aged; Orientia tsutsugamushi; Polymerase Chain Reaction; Rifampin; Scrub Typhus; Sensitivity and Specificity; Time Factors

The influence of tsutsugamushi fever infection on the metabolism of blood lymphocytes of mice differing in susceptibility to Rickettsia tsutsugamushi and of rifampicine and tetracycline treatment was studied. In susceptible mice, the activity of oxidation-reduction processes in lymphocytes increased at 7--10 days of the disease and became normal upon recovery of the animals. In mice with low susceptibility this increase of the activity began and terminated much earlier, at 3--5 days. Treatment of the infection with antibiotics resulted in a rapid arrest of the disease and normalization of the lymphocyte activity. The relationship between susceptibility of the animals to R. tsutsugamushi and the activity of oxidation-reduction enzymes is discussed on the example of succinate dehydrogenase.

Topics: Animals; Antibodies, Bacterial; Disease Models, Animal; Lymphocytes; Mice; Orientia tsutsugamushi; Rifampin; Scrub Typhus; Succinate Dehydrogenase; Tetracycline