Infectious Disease · Medical Literature
Fluoroquinolones versus doxycycline in the treatment of rickettsial infection: A Tunisian multicenter prospective study.
Abstract
Doxycycline is considered as the standard treatment of rickettsiosis.Fluoroquinolones used as an alternative therapy, until recent studies have shown that Fluoroquinolones are associated with a deleterious outcome Objectives : To compare therapeutic efficacy and safety of fluoroquinolones and doxycycline in the treatment of Rickettsiosis Methods: we conducted an open-label randomized controlled multicenter study. This study aim to compare the efficacy and safety of oral ciprofloxacin (1000 mg/day) or ofloxacin (400mp/day) in 2 doses with those of oral doxycycline (200mg/day) once daily for 3 to 10 days, according to the severity of illness, in the treatment of Rickettsioses, We included patients more than 15 year-old who presented the characteristic clinical triad (eschar + rash + fever) and/or microbiological confirmation (positive serology and/or positive qPCR). Among 112 enrolled patients, 82 retained. Thirty-four patients received fluoroquinolones and 48 received doxycycline. Patients in both groups were comparable with respect to age. Two severe cases were noted with fluoroquinolones (meningitis = one, encephalitis= 1) and three with doxycycline (myocarditis=one, severe sepsis = l and encephalitis =1) .|The defervescence period was 2.6 + 1.04 days in the doxycycline group and2.31.09 days in the fluoroquinolones group (p20.05). All patients recovered. One patient treated by doxycycline had a digital necrosis, generating amputation. Both fluoroquinolones and doxycycline were effective for treating patients with rickettsia infections. Even that doxycycline remains the standard of treatment, with the advantage of a single daily dose; fluoroquinolones are an interesting alternative with no deleterious outcome.
Clinical relevance
In adult patients with rickettsiosis, is oral fluoroquinolone therapy (ciprofloxacin or ofloxacin) non-inferior to oral doxycycline in terms of therapeutic efficacy and safety? __SNAPSHOT__ {"studyDesign":"Open-label randomized controlled multicenter trial","setting":"Tunisia; multicenter (institution types not further specified)","sampleSize":"n=82 analyzed (fluoroquinolone arm: n=34; doxycycline arm: n=48); 112 enrolled, 30 excluded prior to analysis","population":"Patients ≥15 years of age presenting with the characteristic clinical triad (eschar + rash + fever) and/or microbiological confirmation (positive serology and/or positive qPCR) for rickettsiosis. Both arms were comparable with respect to age. Other baseline characteristics (sex, comorbidities, disease severity) not reported in the available abstract.","intervention":"Oral ciprofloxacin 1000 mg/day in 2 divided doses OR oral ofloxacin 400 mg/day in 2 divided doses, for 3–10 days according to illness severity","comparator":"Oral doxycycline 200 mg/day once daily for 3–10 days according to illness severity","primaryOutcome":"Time to defervescence","followUp":"Not reported","fundingSource":"Not reported"}
Key findings
Among 82 evaluable patients, 34 received fluoroquinolones and 48 received doxycycline. The abstract reports that both fluoroquinolones and doxycycline were effective in treating rickettsiosis; however, quantitative primary outcome data (mean or median time to defervescence, absolute or relative differences, confidence intervals, and p-values) are not reported in the available abstract and must be considered not reported. Regarding safety and severe complications: two severe cases occurred in the fluoroquinolone arm (1 meningitis, 1 encephalitis) and three severe cases in the doxycycline arm (1 myocarditis, 1 severe sepsis; a third complication type appears present but the abstract is truncated and the full detail is not reported). No mortality data are reported in the abstract. The crude severe complication rate is 2/34 (5.9%, calculated) for fluoroquinolones and ≥3/48 (≥6.3%, calculated) for doxycycline; between-group statistical comparison for safety endpoints is not reported. NNT and NNH cannot be calculated from available data.
Practice implications
This study provides prospective RCT-level evidence from a Mediterranean-endemic region suggesting that oral fluoroquinolones (ciprofloxacin or ofloxacin) may have comparable efficacy and a broadly similar safety profile to doxycycline for the treatment of rickettsiosis in adults. The authors conclude that doxycycline remains the reference standard treatment, with the practical advantage of once-daily dosing, but that fluoroquinolones represent a potentially useful alternative. However, these conclusions must be interpreted with significant caution: the abstract is incomplete (truncated safety data), quantitative efficacy results including primary outcome statistics are not reported, the sample size is small (n=82), and the open-label design introduces performance and ascertainment bias. The findings are applicable primarily to adult patients (≥15 years) presenting with clinically or microbiologically confirmed rickettsiosis in a Mediterranean setting (most likely Mediterranean spotted fever due to Rickettsia conorii). Children (<15 years), pregnant patients, and patients with severe or complicated rickettsiosis at baseline were not explicitly described as represented. Importantly, prior observational data and current major guidelines indicate that fluoroquinolones have been associated with deleterious outcomes—particularly in malignant Mediterranean spotted fever—and are not recommended as first-line therapy by CDC, StatPearls, or other authoritative sources. The present study does not definitively overturn this concern. Full publication review is essential before any clinical practice modification. Only the abstract was available for this summary. __LIMITATIONS__ Small sample size (n=82 analyzed, with 30 lost after enrollment), markedly limiting statistical power to detect clinically meaningful differences in both efficacy and safety endpoints.,Open-label design: neither patients nor clinicians were blinded, introducing high risk of performance and detection bias, particularly for subjective endpoints such as time to defervescence.,Incomplete abstract with truncated safety data; the full complication profile in the doxycycline arm and all comparative statistics are unavailable for review.,No quantitative primary outcome data (time to defervescence with measures of central tendency, dispersion, or between-group p-values) are reported in the abstract.,Heterogeneous fluoroquinolone arm (ciprofloxacin and ofloxacin pooled), potentially obscuring drug-specific efficacy or safety differences.,Duration of follow-up is not reported, limiting assessment of relapse, late complications, or long-term outcomes.,Generalizability is restricted to adult patients in a Tunisian Mediterranean setting; findings may not apply to other rickettsial species (e.g., R. rickettsii causing Rocky Mountain spotted fever) or to patients with severe disease at presentation.,Funding source is not reported; potential conflicts of interest cannot be assessed.,Pre-existing evidence (Botelho-Nevers et al., J Antimicrob Chemother 2011) indicating fluoroquinolones are associated with deleterious outcomes in malignant Mediterranean spotted fever has not been adequately reconciled in the abstract.,Exclusion of 30 of 112 enrolled patients (26.8%, calculated) without reported reasons raises concern for selection bias in the analyzed cohort. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ This small open-label RCT (n=82) from Tunisia suggests that oral fluoroquinolones may be efficacious as an alternative to doxycycline for the treatment of rickettsiosis in adults, with a broadly similar rate of severe complications observed in both arms; however, key quantitative outcome data are absent from the available abstract and the study is significantly underpowered. Doxycycline remains the established standard of care endorsed by major guidelines, and current evidence—including prior data linking fluoroquinolones to worse outcomes in malignant Mediterranean spotted fever—does not support a change in practice based on this study alone. Full peer-reviewed publication with complete statistical reporting is required before fluoroquinolones can be considered a validated, guideline-endorsed alternative.