Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia

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However, in cases of lepromatous (LL) and borderline lepromatous (BL) patients with high bacterial loads and complicated circumtances, prolonged duration treatment is more often observed. As prolonged duration may affect patient adherence negatively, adding ofloxacin to MDT is a promising approach to prevent prolonged treatment. Method This retrospective cohort study investigated the effects of adding ofloxacin to MDT in 21 patients diagnosed with LL or BL leprosy at Cipto Mangunkusumo National Referral Hospital, Jakarta, Indonesia. Bacterial load and viability were tracked using the Bacteriological Index (BI) and Morphological Index (MI), and were compared using non-parametric Friedman test before and after the patients were given ofloxacin. Findings Adding ofloxacin to MDT led to a significant reductions in both BI and MI. The median MI dropped to zero after six months of combined treatment (p<0.001), with significant differences between baseline and 6, 9, and 12-months. BI also significantly declined (p=0.007), with significant reductions between baseline and 3, 6, 9, and 12-month assessments. The proportion of patients reaching an MI of zero also steadily increased. Interpretation Ofloxacin as an adjunctive therapy to MDT substantially improves treatment of leprosy with high bacterial and morphological index. Faster bacterial clearance prevent prolonged treatment duration, potentially improving adherence, outcomes and reducing relapse risk. Ofloxacin is the only second-line leprosy treatment covered by the national health insurance in Indonesia. Earlier initiation of this adjunctive therapy may offer greater benefits. 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F1000Research 2025, 14 :252 ( https://doi.org/10.12688/f1000research.161758.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia [version 1; peer review: 1 approved with reservations] Mufqi Handaru Priyanto https://orcid.org/0000-0001-9838-6623 1,2 , Malika Sabrina Yunifananda 1 , Sri Linuwih SW Menaldi 1,3 , Erni Juwita Nelwan 3,4 , Melani Marissa 1,3 Mufqi Handaru Priyanto https://orcid.org/0000-0001-9838-6623 1,2 , Malika Sabrina Yunifananda 1 , [...] Sri Linuwih SW Menaldi 1,3 , Erni Juwita Nelwan 3,4 , Melani Marissa 1,3 PUBLISHED 03 Mar 2025 Author details Author details 1 Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, Depok, West Java, Indonesia 2 Universitas Indonesia Hospital, Depok, West Java, Indonesia 3 Rumah Sakit Dr Cipto Mangunkusumo, Central Jakarta, Jakarta, Indonesia 4 Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Depok, West Java, Indonesia Mufqi Handaru Priyanto Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Malika Sabrina Yunifananda Roles: Data Curation, Formal Analysis, Methodology, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sri Linuwih SW Menaldi Roles: Conceptualization, Data Curation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Erni Juwita Nelwan Roles: Conceptualization, Data Curation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Melani Marissa Roles: Conceptualization, Data Curation, Methodology, Writing – Original Draft Preparation OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Pathogens gateway. Abstract Background Standard multi-drug therapy (MDT) with duration of 6-12 months is generally effective for treating leprosy. However, in cases of lepromatous (LL) and borderline lepromatous (BL) patients with high bacterial loads and complicated circumtances, prolonged duration treatment is more often observed. As prolonged duration may affect patient adherence negatively, adding ofloxacin to MDT is a promising approach to prevent prolonged treatment. Method This retrospective cohort study investigated the effects of adding ofloxacin to MDT in 21 patients diagnosed with LL or BL leprosy at Cipto Mangunkusumo National Referral Hospital, Jakarta, Indonesia. Bacterial load and viability were tracked using the Bacteriological Index (BI) and Morphological Index (MI), and were compared using non-parametric Friedman test before and after the patients were given ofloxacin. Findings Adding ofloxacin to MDT led to a significant reductions in both BI and MI. The median MI dropped to zero after six months of combined treatment (p<0.001), with significant differences between baseline and 6, 9, and 12-months. BI also significantly declined (p=0.007), with significant reductions between baseline and 3, 6, 9, and 12-month assessments. The proportion of patients reaching an MI of zero also steadily increased. Interpretation Ofloxacin as an adjunctive therapy to MDT substantially improves treatment of leprosy with high bacterial and morphological index. Faster bacterial clearance prevent prolonged treatment duration, potentially improving adherence, outcomes and reducing relapse risk. Ofloxacin is the only second-line leprosy treatment covered by the national health insurance in Indonesia. Earlier initiation of this adjunctive therapy may offer greater benefits. READ ALL READ LESS Keywords Lepromatous Leprosy; Ofloxacin; Multi-Drug Therapy (MDT); Bacteriological Index (BI); Morphological Index (MI); Leprosy Treatment Optimization; Indonesia Corresponding Author(s) Mufqi Handaru Priyanto ( [email protected] ) Close Corresponding author: Mufqi Handaru Priyanto Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Priyanto MH et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Priyanto MH, Yunifananda MS, Menaldi SLS et al. Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :252 ( https://doi.org/10.12688/f1000research.161758.1 ) First published: 03 Mar 2025, 14 :252 ( https://doi.org/10.12688/f1000research.161758.1 ) Latest published: 03 Oct 2025, 14 :252 ( https://doi.org/10.12688/f1000research.161758.4 )  There is a newer version of this article available. Suppress this message for one day. Introduction Despite global efforts to eliminate Leprosy, Indonesia continues to be a country with a high prevalence of the disease, with 17,251 cases reported by the Indonesian Ministry of Health in 2023. The World Health Organization (WHO) recognizes Indonesia as having one of the highest leprosy burden worldwide. 1 In 2024, a total of 413 leprosy cases have been registered at Dr. Cipto Mangunkusumo National Hospital. 2 The more severe and contagious form of leprosy – lepromatous leprosy (LL) and borderline lepromatous leprosy (BL) – are especially concerning due to their high bacterial loads and may lead to significant morbidity if not properly treated. 3 Since 1981, multi-drug therapy (MDT) combining rifampicin, dapsone, and clofazimine by the World Health Organization (WHO) has been used as the standard treatment for leprosy. 4 While MDT is effective, its use alone can lead to prolonged treatment durations, particularly in patients with high bacterial loads, which may contribute to poor adherence. Adding medication to the current regimen could be considered to improve patient’s adherence. 5 Recently, more studies have analyzed the potential of additional antibacterial agents in enhancing the efficacy of MDT for leprosy cases. Ofloxacin, a fluoroquinolone with strong activity against M. leprae , has shown promise when added to standard MDT. One study highlighted the potential benefits of using ofloxacin in leprosy treatment, noting that it is well tolerated and achieves similar bacterial clearance, even when ofloxacin is only administered during the first month. 6 A retrospective study further demonstrated that patients receiving MDT combined with ofloxacin showed good adherence, as no adherence failures was identified among subjects receiving ofloxacin. Additionally, the combination therapy was associated with a lower relapse rate and improved long-term outcomes, supporting its use as a promising option for treating severe leprosy cases. 5 The evaluation of leprosy treatment is typically followed up using two key bacteriological indices: the Bacterial Index (BI), which measures the overall bacterial load in skin smears, and the Morphological Index (MI), which assesses the proportion of viable (solid) bacilli, which depicts treatment efficacy. A significant reduction in both indices over time reflects successful bacterial clearance and a reduced risk of disease transmission and relapse. 7 Certainly, there are specific considerations that should be given while adding ofloxacin to standard MDT treatment, such as: initial high viable infection load that is indicated by a high MI from acid-fast staining of slit-skin smears, persistently positive MI after at least six months therapy of standard MDT, 8 or relapse, diagnosed based on criteria by Linder et al. 9 With above mentioned findings, this study aims to analyse the efficacy of MDT combined with ofloxacin in patients with lepromatous form of leprosy (BL and LL). By assessing the reduction in BI and MI during the course of treatment regimens, the study seeks to determine whether adding ofloxacin enhances MDT’s bacteriological outcomes, leading to faster bacterial clearance and improved patient outcomes. This is particularly important for patients with lepromatous form of leprosy, where the bacterial load is high and conventional MDT may take longer time than standard duration of multibacillary (MB) therapy to achieve bacteriological cure. Methods Study design Between 2020 and 2024, all medical records of eligible patients with lepromatous form leprosy treated at the Dermatology and Venereology Clinic, Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia, were examined in this retrospective cohort study. The cohort study evaluated treatment outcomes by comparing BI & MI parameters in the same patients before and after the initiation of ofloxacin 400 mg once daily as an adjunct therapy. Participants Patients were included if they (1) were diagnosed with leprosy according to WHO criteria; (2) classified as borderline lepromatous (BL) leprosy or lepromatous form of leprosy (LL) based on Ridley-Jopling criteria 10 ; (3) were adults aged ≥18 years at the start of leprosy treatment; and (4) received ofloxacin in addition to the standard multidrug therapy (MDT) regimen under these circumstances: (a) a high initial viable infection load, evidenced by a high MI from acid-fast staining of slit-skin smears; (b) persistently positive MI, typically after ≥6 months of standard MDT; (c) re-positivity of MI; and (d) relapse, diagnosed based on criteria by Linder et al. 8 , 9 To prevent selection biases, patients were excluded if they (1) had missing initial AFB examination data or (2) did not return for follow-up acid-fast bacilli (AFB) examination at least once after three months of additional ofloxacin ( Figure 1 ). Figure 1. Selection of participants for the study. Procedures Patient data were extracted from electronic patients records by authors on October 2024. Patient information related to demographic, clinical presentation, disability status based on WHO disability grading (grade 0 for no disability, grade 1 for loss of sensation but no visible deformity or damage, and grade 2 for visible deformity of damage present), treatment course, microbiology investigations particularly the results from slit-skin smear examination, and also treatment outcome were gathered. At our center, slit-skin smear examinations are routinely performed from six sites (both earlobes and four lesions) every three months in patients with positive initial MI or in cases requiring close monitoring. Smears are processed using Ziehl-Neelsen staining and evaluated for bacterial and morphological indices by a trained technician, under the supervision of a clinical microbiologist. The BI represents the total number of bacilli, measured semi-quantitatively using the Ridley-Jopling logarithmic scale, while the morphological index is the percentage of solid-staining bacilli. After commencing ofloxacin therapy, patients underwent follow up to do acid-fast bacilli (AFB) examination at least once after three months of addition of adjunct therapy. At each visit, dermatology resident performed clinical examination, including assessment for new lesions, nerve involvement and other clinical findings. Slit-skin smears were collected from standard sites to determine the BI and MI according to established procedures. Outcomes The primary outcomes of this study are (1) change in Bacteriological Index (BI) as this measures the bacterial load in skin smears, and (2) change in Morphological Index (MI) for assesses the proportion of viable bacteria in the smears. The secondary outcome of this study is a proportion of patients achieving an MI of zero. Statistical analysis Statistical analyses were conducted using SPSS Statistics 26 (IBM Corp, Armonk, NY, USA ). and visualized using GraphPad Prism 9.0 (GraphPad Software, Inc., San Diego, CA, USA ). Spatial data was visualized using Google My Maps (Google LLC, Mountain View, CA, USA ). Subject characteristics were presented as frequency and percentage for categorical data, while numerical data were reported as mean and standard deviation. The non-parametric Friedman test was performed to compare MI and BI across AFB measurements, with post-hoc Dunn’s test applied to identify significant differences between time points and baseline value.BI across AFB measurements, with post-hoc Dunn’s test applied to identify significant differences between time points and baseline value. Results Sociodemographic and disease characteristics Twenty-one patients met the eligibility criteria and were included in the analysis ( Table 1 ). The majority of the subjects were male (66.7%) and unemployed (42.9%). All patients resided in the Jakarta metropolitan area, with most domiciled in Jakarta province (57.2%) and the remainder in surrounding regions (Tangerang, Bogor, Depok, and Bekasi) ( Figure 2 ). According to the Ridley-Jopling classification, most patients (71.4%) had polar lepromatous (LL) leprosy, while the remaining patients had borderline lepromatous (BL) disease. Notably, one LL patient was diagnosed with histoid leprosy, and another had Lucio’s leprosy. In terms of disability, 11 patients (52.4%) had no disability, 3 patients (14.3%) had grade 1 disability, and 7 patients (33.3%) had grade 2 disability. Additionally, 6 patients (28.6%) had no history of reaction, while 14 patients (66.7%) experienced a type 2 reaction, 1 patient (4.8%) had a type 1 reaction, and 1 patient (4.8%) had Lucio’s phenomenon. Patients received WHO-MDT for a duration of 9 months (median; range 1–31 months) before starting combined therapy with ofloxacin. Table 1. Sociodemographic and disease characteristics of the subjects. Characteristics Values Age 35.3 ± 11.9 Sex Male 14 (66.7%) Female 7 (33.3%) Occupation Unemployed 9 (42.9%) Private-sector employee 5 (23.8%) Student 3 (14.3%) Self-employed 2 (9.5%) Others 2 (9.5%) Domicile Jakarta Special Capital Region 12 (57.2%) Central Jakarta 3 (14.3%) East Jakarta 3 (14.3%) South Jakarta 2 (9.5%) West Jakarta 2 (9.5%) North Jakarta 2 (9.5%) Tangerang 3 (14.3%) Bogor 3 (14.3%) Depok 2 (9.5%) Bekasi 1 (4.8%) Ridley-Jopling classification Borderline lepromatous (BL) 6 (28.6%) Polar lepromatous (LL) 15 (71.4%) Disability Grade 0 11 (52.4%) Grade 1 3 (14.3%) Grade 2 7 (33.3%) Reaction/history of reaction None 6 (28.6) Type 1 1 (4.8) Type 2 13 (61.9) Lucio’s phenomenon 1 (4.8) Figure 2. Patients’ domicile. Morphological index (MI) clearance on MDT combined with ofloxacin A significant reduction in the morphological index (MI) was observed after the addition of ofloxacin to the standard MDT regimen ( Figure 3 , left). The median MI decreased to 0 after six months of ofloxacin treatment. Significant differences were noted across visits (p < 0.001), with post-hoc comparisons showing significant differences between baseline and six months (p = 0.003), nine months (p = 0.014), and 12 months (p = 0.008), but not at three months (p = 0.060). Figure 3. Changes in absolute morphological (left) and bacterial (right) indices before and after ofloxacin addition. Bacterial index (BI) clearance on MDT combined with ofloxacin A consistent and significant reduction in the bacterial index (BI) was also observed following the addition of ofloxacin ( Figure 3 , right). Significant differences were noted across visits (p = 0.007), with pairwise comparisons showing significant reductions in BI between baseline and three months (p = 0.039), six months (p = 0.003), nine months (p = 0.006), and 12 months (p = 0.004). Proportion of patients achieving MI 0 There was a consistent increase in the proportion of patients achieving an MI to 0 following the addition of ofloxacin, demonstrating the treatment’s effectiveness in reducing viable bacterial load over time ( Figure 4 ). Figure 4. Proportion of patients achieving absolute morphological index of 0 before and after the addition of ofloxacin. Discussion This study demonstrated a significant reduction in the morphological index (MI) following the addition of ofloxacin to the standard MDT regimen, and the median MI also decreased to 0 after six months of ofloxacin treatment. This finding aligns with the known bactericidal effects of ofloxacin, a floroquinolone antibiotic that directly kills the bacteria responsible for leprosy rather than merely inhibiting its growth. 11 This characteristic makes ofloxacin highly effective in reducing the bacterial load in leprosy patients, leading to faster clinical improvements and reducing transmission risk. Moreover, ofloxacin has proven effective in both paucibacillary (PB) and multibacillary (MB) forms of leprosy, especially while combined with other potent bactericidal agents like rifampicin and minocycline. 12 While ofloxacin-based multidrug therapy (OMDT) has a similar treatment duration, the fluoroquinolone component may provide better efficacy in the lepromatous form of leprosy cases, as mentioned in the inclusion criteria in this study about clinical indications for initiating ofloxacin, that might require more aggressive approach to achieve high cure rate. 13 The cure rate in this report showed consistent increase in the proportion of patients achieving an MI of 0 following the addition of ofloxacin, demonstrating the treatment’s effectiveness in reducing viable bacterial load over time. This result is similar to other study evaluating OMDT in non-endemic area that showed a high cure rate and tolerability. 5 Other studies evaluating the effectivity of ofloxacin combined with rifampicin and minocycline showed 2-year cure rate which achieved 93.1% to 99%. 14 , 15 Moreover, a clinical trial that followed up for an average 10.8 years after ofloxacin-containing regimen, reported relapse in one out of 58 patients. 16 These findings supported that adding ofloxacin might be a promising alternative to standard WHO MDT, due to the high cure rate reported. Ofloxacin offers a notable advantage in leprosy treatment due to its rapid onset of action, surpassing the effects of several conventional drugs. Studies indicate its efficacy in quickly decreasing the bacterial index (BI), a crucial indicator on monitoring severe or drug resistant leprosy cases. 17 This study’s findings confirm the established efficacy of ofloxacin, demonstrating a significant reduction in the MI, which reflects the proportion of viable bacilli, after the addition to the standard MDT regimen. Specifically, the median MI was observed to reach zero within six months of treatment initiation. The statistical analysis confirmed significant differences in MI across the assessed time points (p < 0.001). Subsequent post-hoc analysis revealed significant differences between baseline and six months (p = 0.003), nine months (p = 0.014), and 12 months (p = 0.008). Previous studies showed ofloxacin daily on lepromatous leprosy patients produced remarkable clinical improvement, rapid and significant decline of the MI, and killing of > 99 and > 99.99% of the viable M. leprae present before treatment by 14 and 28 days, respectively. 18 This is also consistent to the previous observation that administration of ofloxacin resulted in the complete inhibition of bacterial multiplication and no resumption of growth was observed even 18 months after treatment. 19 Another study shows that, compared to MDT-WHO regimen, the decrease of MI score of patients treated with ofloxacin combined with rifampicin and minocycline is more significant, 79.97% of WHO MDT and 94.83% of ROM regimen. 20 In addition to MI, our study also observed consistent and significant reductions in the bacterial index (BI) following the addition of ofloxacin. Significant differences were noted across visits (p = 0.007), with pairwise comparisons showing significant reductions in BI between baseline and three months (p = 0.039), six months (p = 0.003), nine months (p = 0.006), and 12 months (p = 0.004). These findings emphasize the importance of adding ofloxacin to MDT regimens as early as possible, particularly in cases with a high bacterial load or when certain clinical criteria are met. Rapid reductions in both MI and BI not only reflect effective bacterial clearance but also reduce the risk of relapse and disease transmission. 7 Our data suggests that early initiation of ofloxacin, particularly with inclusion criteria as mentioned above, may lead to faster bacterial clearance and improved patient outcomes. Notably, in our study, patients received WHO-MDT for a duration of 9 months (median; range 1-31 months) before starting combined therapy with ofloxacin. However, waiting for 9 months or longer may not be necessary. If the BI and MI are very high, the addition of ofloxacin should be considered as early as possible to achieve a faster decline in BI and MI, thereby shortening the treatment duration, improving adherence, and reducing the risk of treatment discontinuation. Ofloxacin not only enhances bactericidal efficacy but also prevents drug resistance when combined with other antibiotics such as rifampicin, clofazimine, dapsone. This combination also ensures a broad coverage against the bacterium, improving overall treatment outcomes while reducing the risk of resistance, a major concern in long-term leprosy management. 21 Moreover, studies have demonstrated that ofloxacin combined with rifampicin and minocycline produces fewer side effects compared to the MDT-WHO regimen, which may improve patient adherence and treatment success rate. 20 The broader application of ofloxacin is particularly crucial in MB leprosy, where the bacterial load and MI are higher. 22 Studies have demonstrated that combining ofloxacin with minocycline have been shown to be more bactericidal than dapsone and clofazimine in both mice in both mice and clinical trial. 23 This enhanced efficacy underlines the necessity of incorporating ofloxacin into treatment regimens especially in special cases, for instance, the dapsone hypersensitivity syndrome (DHS). 24 DHS is a complication where patients are unable to tolerate dapsone as part of standard MDT. In such cases, the addition of ofloxacin provides a viable alternative to ensure effective bacterial clearance. This clearance is crucial as high BI is one of the risk factors for the occurrence of grade 2 disability. 25 Finally, in cases of drug-resistant leprosy, ofloxacin has been used as an alternative when traditional drugs like dapsone or clofazimine are ineffective. 5 This makes it a critical option in the arsenal against resistant strains of M. leprae , providing hope for patients who may not respond to standard therapies. As leprosy cases become increasingly concentrated in specific regions, the role of newer antibiotics like ofloxacin will likely expand to support global efforts in reducing disease prevalence and preventing disabilities associated with untreated leprosy. 20 This is the first study from Indonesia to evaluate the effectiveness of adding ofloxacin to the standard WHO MDT regimen for leprosy. It is important to note that this approach is applicable only for certain cases, particularly lepromatous form of leprosy patients who meet the following criteria: (1) a high initial viable infection load, as evidenced by a high morphological index (MI) from acid-fast staining of slit-skin smears; (2) persistently positive MI, typically after ≥6 months of standard MDT; (3) re-positivity of MI; and (4) relapse, diagnosed based on criteria by Linder et al. 8 In Indonesia, ofloxacin is currently the only second-line treatment for leprosy covered by the national health insurance system. However, its use is restricted to the national referral hospital and is covered only for one week-long of administration. For the next three weeks of consumption, patients are required to either purchase the medication themselves or visit the hospital weekly to receive it. This limitation emphasizes the need for policy changes to improve access to this promising therapy, particularly for patients in rural areas. We acknowledge that this study was conducted retrospectively and has limitations, including potential for biases to inherent to this design. Additionally, the safety and drug tolerance profile regarding ofloxacin may not have been adequately captured due to limited documentation in these records. Despite these limitations, we believe that our findings could be a preliminary data for the future randomized control trial study with larger sample size to evaluate the efficacy of ofloxacin in lepromatous form of leprosy thoroughly. Conclusion Addition of ofloxacin to standard MDT WHO in lepromatous form of leprosy patients significantly reduces both in the MI and BI after six months and three months, respectively. Addition of ofloxacin also demonstrated the treatment’s effectiveness in reducing viable bacterial load over time. Ethics and consent The study protocol was reviewed and approved by the Ethics Committee of the Faculty of Medicine, Universitas Indonesia – Dr. Cipto Mangunkusumo Hospital (Komite Etik Penelitian Kesehatan Fakultas Kedokteran Universitas Indonesia – RSUPN Dr. Cipto Mangunkusumo). The approval date was December 8, 2024, valid for one year from the date of approval. The protocol number assigned to this study is KET-1769/UN2.F1/ETIK/PPM.00.02/2024. As this research involved retrospective secondary data extracted from medical records, no direct patient contact was required. Consequently, the need for individual informed consent specific to this study was waived by the Ethics Committee. However, all patients at Dr. Cipto Mangunkusumo Hospital provide general consent for treatment and the use of their data for research purposes upon admission, with strict adherence to anonymity, and in accordance with all relevant regulations and ethical standards. Contributors MHP: Conceptualisation, data curation, methodology, statistical analysis, visualisation, writing (original draft and revisions) MSY: Data curation, methodology, statistical analysis, visualisation, writing (original draft and revisions) SLM: Conceptualisation, data curation, methodology, writing (original draft and revisions) EJN: Conceptualisation, data curation, methodology, writing (original draft and revisions) MM: Conceptualisation, data curation, methodology, writing (original draft and revisions) Data availability Underlying data Figshare: Dataset OMDT.xlsx. https://doi.org/10.6084/m9.figshare.28331675.v1 . 26 The project contains the following underlying data: • Dataset OMDT.xlsx Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Software availability To facilitate accessibility for future studies, we note the following open-source alternatives, such as JASP (JASP Team, Amsterdam, Netherlands) for statistical analyses and ggplot2 3.5.1 (Hadley Wickham, Auckland, New Zealand ) or SciDAVis (SciDAVis Development Team) for data visualization. References 1. World Health Organizations: Global leprosy (Hansen disease) update, 2023: Elimination of leprosy disease is possible - Time to act! Wkly Epidemiol. Rec. 2024; 1 (37): 501–521. 2. Departemen Dermatologi dan Venereologi: Jumlah Kasus Kusta di RS Dr. Cipto Mangunkusumo Jakarta. Jakarta: 2024. 3. Ridley DS, Jopling WH: Classification of leprosy according to immunity. A five-group system. Int. J. Lepr. Other Mycobact. Dis. 1966; 34 (3): 255–273. PubMed Abstract 4. Lazo-Porras M, Prutsky GJ, Barrionuevo P, et al. : World Health Organization (WHO) antibiotic regimen against other regimens for the treatment of leprosy: A systematic review and meta-analysis. BMC Infect. Dis. 2020; 20 : 62. BioMed Central Ltd. PubMed Abstract | Publisher Full Text | Free Full Text 5. Faust L, Klowak M, MacRae C, et al. : Ofloxacin-containing multidrug therapy in ambulatory leprosy patients: a case series. J. Cutan. Med. Surg. 2020; 25 : 45–52. Publisher Full Text 6. Khang TH, Panikar V, Lanh PH, et al. : Treatment of leprosy with ofloxacin - containing combined drug regimens in vietnam. Madridge J. Dermatology Res. 2019 May 20; 4 (1): 96–99. Publisher Full Text 7. Pattyn SR: Activity of ofloxacin and pefloxacin against mycobacterium leprae in mice. Antimicrob. Agents Chemother. 1987; 31 (4): 671–672. PubMed Abstract | Publisher Full Text | Free Full Text 8. Narang T, Bishnoi A, Dogra S, et al. : Alternate anti-leprosy regimen for multidrug therapy refractory leprosy: A retrospective study from a tertiary care center in North India. Am. J. Trop. Med. Hyg. 2019; 100 (1): 24–30. PubMed Abstract | Publisher Full Text | Free Full Text 9. Linder K, Zia M, Kern WV, et al. : Relapses vs. reactions in multibacillary leprosy: Proposal of new relapse criteria. Trop. Med. Int. Health. 2008 Mar; 13 (3): 295–309. PubMed Abstract | Publisher Full Text 10. Ridley DS, Jopling WH: Classification of leprosy according to immunity. A five-group system. Int. J. Lepr. Other Mycobact. Dis. 1966; 34 (3): 255–273. PubMed Abstract 11. Graham DB, Tripp J: Ofloxacin. Vol. 1 . . Treasure Island (FL): StatPearls Publishing; 2023; 1–10. 12. Widjaja Y, Djawad K, Amin S, et al. : Alternative leprosy treatment using rifampicin ofloxacin minocycline (rom) regimen – two case reports. Serb. J. Dermatol. Venerol. 2019 Sep 1; 11 (3): 89–93. Publisher Full Text 13. Cunha AS, Virmond M, Schettini AP, et al. : Ofloxacin multicentre trial in MB leprosy FUAM-Manaus and ILSL-Bauru, Brazil. Lepr. Rev. 2012; 1 (83): 261–268. 14. Girdhar A, Kumar A, Girdhar KB: A randomised controlled trial assessing the effect of adding clarithromycin to rifampicin, ofloxacin and minocycline in the treatment of single lesion paucibacillary leprosy in Agra District, India. Lepr. Rev. 2011; 82 (1): 46–54. PubMed Abstract | Publisher Full Text 15. Kumar A, Girdhar A, Girdhar B: A randomized controlled trial to compare cure and relapse rate of paucibacillary multidrug therapy with monthly rifampicin, ofloxacin, and minocycline among paucibacillary leprosy patients in Agra District, India. Indian J. Dermatol. Venereol. Leprol. 2015; 81 (4): 356–362. PubMed Abstract | Publisher Full Text 16. Balagon MF, Cellona RV, Abalos RM, et al. : The efficacy of a four-week, ofloxacin-containing regimen compared with standard WHO-MDT in PB leprosy. Lepr. Rev. 2010; 1 (81): 27–33. 17. Rao PS, Ramachandran A, Sekar B, et al. : Ofloxacin-containing combined drug regimens in the treatment of lepromatous leprosy. Lepr. Rev. 1994; 65 : 181–189. PubMed Abstract 18. Ji B, Perani EG, Petinom C, et al. : Clinical trial of ofloxacin alone and in combination with dapsone plus clofazimine for treatment of lepromatous leprosy. Antimicrob. Agents Chemother. 1994; 38 (4): 662–667. PubMed Abstract | Publisher Full Text | Free Full Text 19. Grosset JH, Guelpa-Lauras CC, Perani EG, et al. : Activity of ofloxacin against mycobacterium leprae in the mouse. Int. J. Lepr. 1988; 56 (2): 259–264. 20. Moestopo O, Gunawan H, Dahlan A: Comparison of effectiveness between rifampicin ofloxin-minocycline regimen and multidrug therapy-world health organization in multibacillary leprosy patients. Althea Med. J. 2016; 3 (4): 661–665. Publisher Full Text 21. World Health Organization: WHO Expert Committee on Leprosy: eighth report. World Health Organization; 2012. 22. Basuki S, Rahmi M: Relapse of multibacillary leprosy treated with rifampicin and ofloxacin: a case report. J. Pigment Disord. 2017; 04 (2): 1–3. Publisher Full Text 23. Kar HK, Gupta R: Treatment of leprosy. Clin. Dermatol. 2015; 33 : 55–65. Publisher Full Text 24. Krismawati H, Irwanto A, Pongtiku A, et al. : Validation study of hla-b* 13:01 as a biomarker of dapsone hypersensitivity syndrome in leprosy patients in Indonesia. PLoS Negl. Trop. Dis. 2020; 14 (10): 1–11. Publisher Full Text 25. Mowla MR, Angkur DM, Hasan Z, et al. : Leprosy patients with deformities at post-elimination stage: The Bangladesh experience. Skin Health Dis. 2021; 1 (1): 1–8. Publisher Full Text 26. Handaru Priyanto M, Yunifananda MS, Menaldi SL, et al. : Dataset OMDT.xlsx. Dataset. figshare. 2025. Publisher Full Text Comments on this article Comments (0) Version 4 VERSION 4 PUBLISHED 03 Mar 2025 ADD YOUR COMMENT Comment Author details Author details 1 Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, Depok, West Java, Indonesia 2 Universitas Indonesia Hospital, Depok, West Java, Indonesia 3 Rumah Sakit Dr Cipto Mangunkusumo, Central Jakarta, Jakarta, Indonesia 4 Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Depok, West Java, Indonesia Mufqi Handaru Priyanto Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Malika Sabrina Yunifananda Roles: Data Curation, Formal Analysis, Methodology, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Sri Linuwih SW Menaldi Roles: Conceptualization, Data Curation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Erni Juwita Nelwan Roles: Conceptualization, Data Curation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Melani Marissa Roles: Conceptualization, Data Curation, Methodology, Writing – Original Draft Preparation Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (4) version 4 Revised Published: 03 Oct 2025, 14:252 https://doi.org/10.12688/f1000research.161758.4 version 3 Revised Published: 06 Aug 2025, 14:252 https://doi.org/10.12688/f1000research.161758.3 version 2 Revised Published: 28 Apr 2025, 14:252 https://doi.org/10.12688/f1000research.161758.2 version 1 Published: 03 Mar 2025, 14:252 https://doi.org/10.12688/f1000research.161758.1 Copyright © 2025 Priyanto MH et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Priyanto MH, Yunifananda MS, Menaldi SLS et al. Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :252 ( https://doi.org/10.12688/f1000research.161758.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 03 Mar 2025 Views 0 Cite How to cite this report: Ochoa MT. Reviewer Report For: Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :252 ( https://doi.org/10.5256/f1000research.177837.r369473 ) The direct URL for this report is: https://f1000research.com/articles/14-252/v1#referee-response-369473 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 02 Apr 2025 Maria T Ochoa , Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, Southern California, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.177837.r369473 The work done by Priyanto al is interesting and in my opinion the article adds new insights into the treatment of leprosy in Indonesia The article needs improvements in the methods, results and discussion. - The authors should ... Continue reading READ ALL The work done by Priyanto al is interesting and in my opinion the article adds new insights into the treatment of leprosy in Indonesia The article needs improvements in the methods, results and discussion. - The authors should include a cohort of patients treated with multidrug therapy without ofloxacin. That will improve the quality of the paper -Authors should explain the meaning of “high initial viable infection load, evidenced by a high MI” what is considered a high MI -Authors should mention the main dose used for ofloxacin and also the main side effects of this medication. - The discussion is too long, very repetitive and should be reduced. The findings are interesting, however the authors cannot draw conclusions. The authors need to acknowledge this limitation. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: leprosy I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Ochoa MT. Reviewer Report For: Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :252 ( https://doi.org/10.5256/f1000research.177837.r369473 ) The direct URL for this report is: https://f1000research.com/articles/14-252/v1#referee-response-369473 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 18 Apr 2025 Mufqi Handaru Priyanto , Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia 18 Apr 2025 Author Response We sincerely appreciate the reviewer’s constructive feedback on our manuscript. Below, we address each of the points raised: 1. Regarding the suggestion to include a cohort treated without ofloxacin: ... Continue reading We sincerely appreciate the reviewer’s constructive feedback on our manuscript. Below, we address each of the points raised: 1. Regarding the suggestion to include a cohort treated without ofloxacin: We acknowledge the importance of this comparison. However, as this is a preliminary study, our aim was to analyze treatment outcomes before and after the addition of ofloxacin within the same patient group. Should the current findings prove promising, a subsequent study involving a direct comparison between ofloxacin and non-ofloxacin groups will be conducted to strengthen this finding 2. Regarding the clarification of “high initial viable infection load, evidenced by a high MI”: A high MI (Morphological Index) was not the sole criterion for patient recruitment in this study. While there is currently no universally accepted threshold in the international literature defining what constitutes a "high" MI, we based our observations on patient data from our center. In addition to elevated MI values, other factors such as persistent positivity, relapse, and re-positivity were also considered in selecting subjects for inclusion. 3. Regarding the main dose and side effects of ofloxacin: We have now included a description of the dose of ofloxacin along with its commonly reported side effects 4. Regarding the discussion section: We have revised the discussion section to make it more concise Thank you so much for your time We sincerely appreciate the reviewer’s constructive feedback on our manuscript. Below, we address each of the points raised: 1. Regarding the suggestion to include a cohort treated without ofloxacin: We acknowledge the importance of this comparison. However, as this is a preliminary study, our aim was to analyze treatment outcomes before and after the addition of ofloxacin within the same patient group. Should the current findings prove promising, a subsequent study involving a direct comparison between ofloxacin and non-ofloxacin groups will be conducted to strengthen this finding 2. Regarding the clarification of “high initial viable infection load, evidenced by a high MI”: A high MI (Morphological Index) was not the sole criterion for patient recruitment in this study. While there is currently no universally accepted threshold in the international literature defining what constitutes a "high" MI, we based our observations on patient data from our center. In addition to elevated MI values, other factors such as persistent positivity, relapse, and re-positivity were also considered in selecting subjects for inclusion. 3. Regarding the main dose and side effects of ofloxacin: We have now included a description of the dose of ofloxacin along with its commonly reported side effects 4. Regarding the discussion section: We have revised the discussion section to make it more concise Thank you so much for your time Competing Interests: none Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 18 Apr 2025 Mufqi Handaru Priyanto , Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia 18 Apr 2025 Author Response We sincerely appreciate the reviewer’s constructive feedback on our manuscript. Below, we address each of the points raised: 1. Regarding the suggestion to include a cohort treated without ofloxacin: ... Continue reading We sincerely appreciate the reviewer’s constructive feedback on our manuscript. Below, we address each of the points raised: 1. Regarding the suggestion to include a cohort treated without ofloxacin: We acknowledge the importance of this comparison. However, as this is a preliminary study, our aim was to analyze treatment outcomes before and after the addition of ofloxacin within the same patient group. Should the current findings prove promising, a subsequent study involving a direct comparison between ofloxacin and non-ofloxacin groups will be conducted to strengthen this finding 2. Regarding the clarification of “high initial viable infection load, evidenced by a high MI”: A high MI (Morphological Index) was not the sole criterion for patient recruitment in this study. While there is currently no universally accepted threshold in the international literature defining what constitutes a "high" MI, we based our observations on patient data from our center. In addition to elevated MI values, other factors such as persistent positivity, relapse, and re-positivity were also considered in selecting subjects for inclusion. 3. Regarding the main dose and side effects of ofloxacin: We have now included a description of the dose of ofloxacin along with its commonly reported side effects 4. Regarding the discussion section: We have revised the discussion section to make it more concise Thank you so much for your time We sincerely appreciate the reviewer’s constructive feedback on our manuscript. Below, we address each of the points raised: 1. Regarding the suggestion to include a cohort treated without ofloxacin: We acknowledge the importance of this comparison. However, as this is a preliminary study, our aim was to analyze treatment outcomes before and after the addition of ofloxacin within the same patient group. Should the current findings prove promising, a subsequent study involving a direct comparison between ofloxacin and non-ofloxacin groups will be conducted to strengthen this finding 2. Regarding the clarification of “high initial viable infection load, evidenced by a high MI”: A high MI (Morphological Index) was not the sole criterion for patient recruitment in this study. While there is currently no universally accepted threshold in the international literature defining what constitutes a "high" MI, we based our observations on patient data from our center. In addition to elevated MI values, other factors such as persistent positivity, relapse, and re-positivity were also considered in selecting subjects for inclusion. 3. Regarding the main dose and side effects of ofloxacin: We have now included a description of the dose of ofloxacin along with its commonly reported side effects 4. Regarding the discussion section: We have revised the discussion section to make it more concise Thank you so much for your time Competing Interests: none Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 4 VERSION 4 PUBLISHED 03 Mar 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 4 5 6 Version 4 (revision) 03 Oct 25 read read read Version 3 (revision) 06 Aug 25 read Version 2 (revision) 28 Apr 25 read Version 1 03 Mar 25 read Maria T Ochoa , Keck School of Medicine, University of Southern California, Los Angeles, USA Brandon L Adler , University of Southern California, Los Angeles, USA Fifa Argentina , Universitas Sriwijaya, Palembang, Indonesia Isadora Costa Celestino , Federal University of Uberlândia, Uberlândia, Brazil Bruno de Carvalho Dornelas , Federal University of Uberlândia,, Uberlândia,, Brazil Hongsheng Wang , Nanjing Medical University, Nanjing, China Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Wang H. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 20 Nov 2025 | for Version 4 Hongsheng Wang , Nanjing Medical University, Nanjing, China 0 Views copyright © 2025 Wang H. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions It is recommended to classify the treatment outcomes of patients according to the following baseline conditions: “(a) a high initial viable infection load, evidenced by a high MI from acid-fast staining of slit-skin smears; (b) persistently positive MI, typically after ≥6 months of standard MDT; (c) re-positivity of MI; and (d) relapse.” Regarding Figure 2, the sample size at each time point decreased significantly (n = 21 → 15 → 10 → 7). The authors only compared MI and BI at each follow-up point with the baseline, which may represent inconsistent comparison sets. Were there any cases with a 6-month follow-up but without a 3-month follow-up? It is suggested to also perform comparisons between different time points (e.g., 3 vs 6 months) to avoid missing information related to declining trends and relapse. After reaching MI = 0, was continuous follow-up performed? Were there any cases of “(c) re-positivity of MI” or “(d) relapse”? Using only */ns to indicate significance is insufficient to reflect biological or clinical relevance; median values and 95% confidence intervals should be reported to better interpret the actual magnitude of change. Were there any cases that did not take ofloxacin, used other medications, or received extended MDT regimens? It is recommended to include these cases for comparison. Were there any leprosy reactions during treatment? Were any adverse effects of ofloxacin observed? It is suggested to add relevant descriptions. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? No source data required Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise leprosy control I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Wang H. Peer Review Report For: Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :252 ( https://doi.org/10.5256/f1000research.188786.r421048) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-252/v4#referee-response-421048 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Carvalho Dornelas B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 25 Oct 2025 | for Version 4 Bruno de Carvalho Dornelas , Federal University of Uberlândia,, Uberlândia,, Brazil 0 Views copyright © 2025 Carvalho Dornelas B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This study, a single-center retrospective cohort analysis, investigates the efficacy of adding ofloxacin (400 mg once daily) to the standard WHO Multi-Drug Therapy (MDT) regimen for patients diagnosed with lepromatous (LL) or borderline lepromatous (BL) leprosy (N=21). The primary objective was to assess the impact of this adjunctive therapy on bacteriological outcomes, specifically measuring the Morphological Index (MI) and the Bacteriological Index (BI). The authors found a significant reduction in both MI and BI after the addition of ofloxacin, noting that the median MI dropped to zero after six months of combined treatment. This outcome is interpreted as supporting the potent bactericidal activity of ofloxacin, leading to faster bacterial clearance in high-bacterial-load cases, potentially enhancing adherence and reducing relapse risk. Standard multi-drug therapy (MDT) with duration of 6-12 months is generally effective for treating leprosy . WHO/MDT dates from 80s. We need new drugs as ofloxacin. Relapse and treatment failure rates are not low. Could you please cite: [Nascimento ACMD, et al (2022) - Ref 1] Despite global efforts to eliminate Leprosy . Please, keep it in lowercase (leprosy). where the bacterial load is high and conventional MDT may take longer time than standard duration of multibacillary (MB) therapy to achieve bacteriological cure . How do you define bacteriological cure? Please, exclusion criteria do not make sense. Having the available data in an inclusion criterion, isn’t it? Exclusion criteria are not the opposite of those. Maybe, patients with other infectious disease were exclude…. Please, note this. At each visit, dermatology resident? No supervision from a senior dermatologist? Nearly half of the initial patients (N=43) were excluded due to missing data or failure to return for follow-up. This high attrition rate in a retrospective single-center study limits the generalizability of the findings to broader populations and introduces potential selection bias. This limitation is noted by the authors and should be continuously emphasized. For future research, as the authors mention, strategies must be implemented to ensure prospective data collection and patient retention for long-term chronic disease follow-up. The work addresses a clinically relevant challenge: the optimization of treatment for highly bacilliferous forms of leprosy (LL/BL) where standard MDT alone may lead to prolonged viable infection and potential issues with adherence or relapse. The use of BI and MI as primary bacteriological outcomes is appropriate for assessing treatment efficacy. However, as highlighted by multiple reviewers, the study design presents significant methodological limitations that restrict the strength and generalizability of the conclusions. The study primarily measures change within the same cohort after the introduction of ofloxacin, making it difficult to definitively attribute the acceleration of clearance entirely to the added drug, rather than the ongoing effects of standard MDT. The most substantial weakness is the absence of a concurrent control group receiving standard MDT without ofloxacin. This retrospective design limits the ability to compare outcomes directly, preventing the authors from asserting that the observed acceleration in bacterial clearance (MI and BI reduction) is significantly faster than what would have occurred naturally with standard MDT in this specific population. While the authors explained that ethical considerations at a national referral center precluded withholding potentially beneficial treatment from high-risk patients solely for a comparison group, this needs to be emphasized more strongly as a limitation when interpreting results. The language used in the Abstract—suggesting the approach helps "prevent prolonged treatment duration"—must be tempered, as the Discussion noted that the overall duration remained similar, but the efficacy was enhanced. The authors should clarify the focus: is the main goal shortening the duration, or achieving bacteriological cure faster within the standard timeframe? The primary outcomes of this study are (1) change in Bacteriological Index (BI) as this measures the bacterial load in skin smears, and (2) change in Morphological Index (MI) . Please, once abbreviated, keep using abbreviations throughout the text. The majority of the subjects were male (66.7%) and unemployed (42.9%). Please, rewrite this. 42,9% is not the majority, is it? The monitoring of adverse effects was primarily passive, relying on documentation in medical records if patients reported complaints, rather than a systematic evaluation. This is inadequate, especially given that ofloxacin is known to cause serious side effects like tendinopathy and peripheral neuropathy. The absence of documentation does not guarantee the absence of adverse effects. Future, more thorough studies should incorporate a systematic and active monitoring protocol for known adverse effects associated with ofloxacin, particularly musculoskeletal and neurological complications. Studies of the rifampicin-ofloxacin-minocycline (ROM) combination reported 2-year cure rate ranging from 93.1% to 99%. What is cure in leprosy? What are the criteria for it? I am not aware of any. Ofloxacin was initiated under circumstances including a "high initial viable infection load, evidenced by a high MI". The authors should explicitly define the internal threshold or clinical criteria used that qualified an MI result as "high" enough to warrant immediate addition of second-line therapy, thereby providing crucial context for replication. The article presents useful preliminary data supporting the use of ofloxacin as an adjunctive treatment for high-bacterial-load leprosy, demonstrating faster bacteriological clearance. The importance of optimizing treatment for these challenging cases is clear. However, significant methodological limitations inherent to the retrospective design and the passive nature of adverse effects monitoring weaken the conclusiveness and generalizability of the results. Please: 1. Ensure the interpretation of the findings consistently reflects the limitations inherent to the retrospective, single-center, non-controlled design. 2. Explicitly define the criteria used by the center to determine a "high MI" that justified the addition of ofloxacin to the standard MDT. 3. Ensure the Introduction/Abstract clearly states that the benefit of Ofloxacin is accelerating clearance, rather than definitively preventing prolonged treatment duration, unless the data unequivocally supports a shorter course. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly References 1. Nascimento A, dos Santos D, Antunes D, Gonçalves M, et al.: Leprosy Relapse: A Retrospective Study on Epidemiologic, Clinical, and Therapeutic Aspects at a Brazilian Referral Center. International Journal of Infectious Diseases . 2022; 118 : 44-51 Publisher Full Text 2. de Carvalho Dornelas B, da Costa W, de Abreu J, Daud J, et al.: Role of histopathological, serological and molecular findings for the early diagnosis of treatment failure in leprosy. BMC Infectious Diseases . 2024; 24 (1). Publisher Full Text 3. de Carvalho Dornelas B, da Costa W, de Abreu J, Daud J, et al.: Impact of histopathological and serological assessments on early diagnosis of leprosy relapse. APMIS . 2025; 133 (1). Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Pathology and epidemiology and leprosy I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Carvalho Dornelas Bd. Peer Review Report For: Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :252 ( https://doi.org/10.5256/f1000research.188786.r421040) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-252/v4#referee-response-421040 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Celestino I. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 25 Oct 2025 | for Version 4 Isadora Costa Celestino , Federal University of Uberlândia, Uberlândia, Brazil 0 Views copyright © 2025 Celestino I. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I believe the study was conducted appropriately, considering its design, and that important points regarding the efficacy of ofloxacin combined with MDT were discussed, particularly the report of a decrease in BI and MI over time. However, I would like to make a few observations: 1. In the paragraph "A retrospective study further demonstrated that patients receiving MDT combined with ofloxacin showed good adherence, but no adherence failures were identified among subjects receiving ofloxacin. Additionally, the combination therapy was associated with a lower relapse rate and improved long-term outcomes, supporting its use as a promising option for treating severe leprosy cases."5, the study "Faust L, et al., 2021 [Ref- 1]" did not conclude that the use of ofloxacin increases adherence. Rather, it indicated that OMDT helped to reduce some of the existing barriers related to medication, compared to the numerous ones usually encountered. 2. What was the MI cutoff (in percentage) used to define "a high initial viable infection load, evidenced by a high MI from acid-fast staining of slit-skin smears"? I suggest making this explicit. 3. Were there no adverse reactions described in the records? If not, I suggest mentioning this explicitly in the results. Even if this absence is part of the study design as a bias, the methodology section indicates that adverse reaction were monitored. Therefore, it would be helpful to clearly state that no adverse reactions were observed. I believe that once the authors evaluate these points, the article will be even more complete. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes References 1. Faust L, Klowak M, MacRae C, Kopalakrishnan S, et al.: Ofloxacin-Containing Multidrug Therapy in Ambulatory Leprosy Patients: A Case Series. Journal of Cutaneous Medicine and Surgery . 2021; 25 (1): 45-52 Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Pharmacovigilance, Leprosy, Clinical Pharmacy, Pharmacology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Celestino IC. Peer Review Report For: Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :252 ( https://doi.org/10.5256/f1000research.188786.r421045) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-252/v4#referee-response-421045 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Argentina F. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 03 Sep 2025 | for Version 3 Fifa Argentina , Universitas Sriwijaya, Palembang, South Sumatra, Indonesia 0 Views copyright © 2025 Argentina F. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The study highlights ofloxacin’s potential to accelerate bacteriological clearance in lepromatous leprosy, but methodological issues limit its strength. Lack of a control group, retrospective single-center design, and substantial missing follow-up reduce generalizability. Discussion remains repetitive, adverse event monitoring was inadequate, and inconsistencies in patient selection should be clarified. Thank you. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise The use of standard leprosy drugs in some cases is often resistant, characterized by unchanged bacterial index and morphology index values or only a slight decrease. This results in longer MDT drug use and reduced patient compliance with medication. With preliminary research on the use of ofloxacin, it can be used as a guideline for further research in the future. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (1) Author Response 03 Oct 2025 Mufqi Handaru Priyanto, Universitas Indonesia Hospital, Depok, Indonesia We thank the reviewer for the constructive comments. Concerning the absence of a control group and the retrospective single-center design, we acknowledge that this limits the generalizability of the findings; this has already been addressed in the Limitations section, and we have strengthened our interpretation by referencing comparable published studies. Regarding adverse event monitoring, we would like to clarify that side effects were monitored through patient medical records during follow-up visits. Any adverse events related to treatment would have been documented in the patient’s status notes, while the absence of such documentation indicated no adverse events. To make this explicit, we have added a statement in the Methods section specifying that adverse event monitoring was integrated into clinical follow-up and recorded accordingly. In addition, the Discussion section has been revised to reduce repetition and improve clarity while maintaining alignment with the cited literature. We believe these revisions address the reviewer’s concerns and strengthen the manuscript View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Argentina F. Peer Review Report For: Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :252 ( https://doi.org/10.5256/f1000research.186135.r407739) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-252/v3#referee-response-407739 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Adler B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 13 Jun 2025 | for Version 2 Brandon L Adler , Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA 0 Views copyright © 2025 Adler B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Thank you for this study evaluating the impact of addition of ofloxacin to MDT for lepromatous leprosy, conducted in a single center. “At our center, slit-skin smear examinations are routinely performed from six sites (both earlobes and four lesions) every three months in patients with positive initial MI or in cases requiring close monitoring.” Accordingly, there seems to be no reason that a cohort of patients receiving MDT without ofloxacin from your center could be compared to those receiving ofloxacin with regard to the BI and MI. That is what is missing for this study to be truly clinically meaningful. In the abstract you state, “As prolonged duration may affect patient adherence negatively, adding ofloxacin to MDT is a promising approach to prevent prolonged treatment.” In the discussion: “Though the treatment duration remains similar to standard MDT, ofloxacin-added regimens may offer enhanced efficacy, particularly in lepromatous cases.” These statements seem contradictory, and maybe the one in the abstract should be toned down? Statistical methods (non-parametric Friedman test) can be deleted from the study abstract. Methods: “The most common adverse effect of this drug is tendinopathy, and there may be hypersensitivity reactions, central nervous system adverse drug reactions, peripheral neuropathy, though uncommon.” This is not a study method and does not belong in this section of the paper. It can go in the introduction (assuming you report the numbers of patients developing side effects to ofloxacin) or in the discussion (since it seems side effects were not evaluated- which is another limitation). In figure 1, I don’t understand how 3 patients were excluded due to not having BL/LL leprosy, if the initial N=43 includes only lepromatous patients. Also in figure 1, we can see that nearly half of patients were excluded due to missing data or not returning for follow up, a major limitation. Figure 2 showing the map of patients’ domiciles is extraneous to the study aims and can be deleted. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? No Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise leprosy I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (1) Author Response 18 Aug 2025 Mufqi Handaru Priyanto, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia Thank you for this study evaluating the impact of addition of ofloxacin to MDT for lepromatous leprosy, conducted in a single center. “At our center, slit-skin smear examinations are routinely performed from six sites (both earlobes and four lesions) every three months in patients with positive initial MI or in cases requiring close monitoring.” Accordingly, there seems to be no reason that a cohort of patients receiving MDT without ofloxacin from your center could be compared to those receiving ofloxacin with regard to the BI and MI. That is what is missing for this study to be truly clinically meaningful. Thank you for this observation. We acknowledge that the inclusion of a control group receiving standard MDT without ofloxacin would indeed strengthen the study's design and enhance its clinical meaningfulness, allowing for a more direct comparison of bacteriological indices (BI) and morphological indices (MI) changes. However, it is crucial to clarify the ethical and practical considerations at our center that led to the current study design. Our institution, as a national referral hospital, primarily manages complex and challenging cases of leprosy, including those with high initial MI, persistent positivity, relapse, or re-positivity, where the standard MDT alone might be insufficient to achieve optimal clinical and bacteriological clearance within the conventional timeframe. The decision to add ofloxacin in these specific cases is a clinical judgment made in accordance with the severity of the disease and the need for more aggressive bacteriological clearance to prevent further complications and transmission. Therefore, withholding an additional, potentially beneficial, antimicrobial agent from these high-risk patients solely for research comparison was considered as ethically unfeasible, given the established clinical practice and patient well-being priorities. While a concurrent control group was not feasible, we aimed to demonstrate the efficacy of ofloxacin-added regimens within this cohort by observing significant reductions in MI and BI over time, and by comparing these outcomes against the expected prolonged treatment durations typically observed in such cases under standard MDT alone. We agree that future multi-center studies, perhaps with different patient populations or in settings where such a comparative arm is ethically permissible, would be invaluable to further validate our findings. In the abstract you state, “As prolonged duration may affect patient adherence negatively, adding ofloxacin to MDT is a promising approach to prevent prolonged treatment.” In the discussion: “Though the treatment duration remains similar to standard MDT, ofloxacin-added regimens may offer enhanced efficacy, particularly in lepromatous cases.” These statements seem contradictory, and maybe the one in the abstract should be toned down? We appreciate you highlighting this discrepancy. You are correct that the statements regarding treatment duration could appear contradictory. We have revised the abstract to better reflect the findings and align with the discussion. In the abstract, our initial statement 'As prolonged duration may affect patient adherence negatively, adding ofloxacin to MDT is a promising approach to prevent prolonged treatment' was an initial hypothesis and a general clinical rationale. However, as revealed in our results and discussed in detail, the addition of ofloxacin did not, in this specific cohort, shorten the overall treatment duration compared to the minimum standard MDT for lepromatous leprosy. Instead, its benefit lies in accelerating bacteriological clearance within that standard duration, which is crucial for preventing relapse and reducing transmission, especially in difficult-to-treat cases. Therefore, we have revised the abstract statement on the newest version. 2. Statistical methods (non-parametric Friedman test) can be deleted from the study abstract. We concur with your suggestion. The specific mention of 'non-parametric Friedman test' in the abstract is indeed overly detailed for this section. We have removed it from the abstract to maintain conciseness and focus on the primary findings, while ensuring the full details of our statistical analysis remain in the Methods section. 3. Methods: “The most common adverse effect of this drug is tendinopathy, and there may be hypersensitivity reactions, central nervous system adverse drug reactions, peripheral neuropathy, though uncommon.” This is not a study method and does not belong in this section of the paper. It can go in the introduction (assuming you report the numbers of patients developing side effects to ofloxacin) or in the discussion (since it seems side effects were not evaluated- which is another limitation). We appreciate this astute observation regarding the placement of the adverse effect description. You are absolutely correct that this information does not belong in the Methods section, which should be reserved for how the study was conducted. We have moved the description of ofloxacin's common adverse effects, including tendinopathy, hypersensitivity reactions, CNS adverse drug reactions, and peripheral neuropathy, to the Introduction section . This provides essential background information for readers regarding the drug's safety profile before they delve into our findings. Regarding the evaluation of side effects in our study, we acknowledge this as a limitation. While we did not conduct a systematic, pre-specified evaluation of all potential adverse effects, any reported side effects during treatment were documented in patient medical records. However, due to the retrospective nature of some data collection and the primary focus on bacteriological outcomes, a comprehensive analysis of adverse events was beyond the scope of this particular study. We have explicitly stated this as a limitation in the Discussion section, consistent with your feedback. 4. In figure 1, I don’t understand how 3 patients were excluded due to not having BL/LL leprosy, if the initial N=43 includes only lepromatous patients. Also in figure 1, we can see that nearly half of patients were excluded due to missing data or not returning for follow up, a major limitation. Thank you for pointing out the inconsistencies in Figure 1. We apologize for the confusion. Regarding the initial cohort of 43 patients and the subsequent exclusions, it is important to clarify our patient selection process. The initial N=43 represents all leprosy patients who received ofloxacin in addition to standard MDT at our center during the study period, as identified from our pharmacy records. From this initial pool, patients were then filtered based on our specific inclusion criteria for this study, which required a diagnosis of lepromatous leprosy (BL/LL). During a re-review of their detailed clinical and histopathological records for this specific study, 3 patients, despite an initial classification, were found to have clinical features and biopsy results that did not unequivocally meet the criteria for the lepromatous (BL/LL) spectrum as defined for our study's inclusion. We have revised the flowchart to clarify this specific reason for exclusion. We fully agree with your observation that the exclusion of nearly half of the patients due to missing data or not returning for follow-up represents a significant limitation. We have acknowledged and emphasized this point more strongly in our Discussion section. This high reduction rate is indeed a challenge inherent to real-world clinical data collection in a referral setting, particularly for chronic diseases requiring long-term follow-up. While regrettable, we believe the remaining robust dataset still provides valuable insights into the efficacy of ofloxacin in the responsive patients within this challenging group. We are actively working on strategies to improve patient retention and data completeness in future studies. 5. Figure 2 showing the map of patients’ domiciles is extraneous to the study aims and can be deleted. We concur with your assessment that Figure 2 is extraneous to the core aims of this study, which primarily focus on the clinical and bacteriological outcomes of the treatment regimen. We have removed Figure 2 from the manuscript. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Adler BL. Peer Review Report For: Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :252 ( https://doi.org/10.5256/f1000research.180812.r384857) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-252/v2#referee-response-384857 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Ochoa M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 02 Apr 2025 | for Version 1 Maria T Ochoa , Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, Southern California, USA 0 Views copyright © 2025 Ochoa M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The work done by Priyanto al is interesting and in my opinion the article adds new insights into the treatment of leprosy in Indonesia The article needs improvements in the methods, results and discussion. - The authors should include a cohort of patients treated with multidrug therapy without ofloxacin. That will improve the quality of the paper -Authors should explain the meaning of “high initial viable infection load, evidenced by a high MI” what is considered a high MI -Authors should mention the main dose used for ofloxacin and also the main side effects of this medication. - The discussion is too long, very repetitive and should be reduced. The findings are interesting, however the authors cannot draw conclusions. The authors need to acknowledge this limitation. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise leprosy I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 18 Apr 2025 Mufqi Handaru Priyanto, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia We sincerely appreciate the reviewer’s constructive feedback on our manuscript. Below, we address each of the points raised: 1. Regarding the suggestion to include a cohort treated without ofloxacin: We acknowledge the importance of this comparison. However, as this is a preliminary study, our aim was to analyze treatment outcomes before and after the addition of ofloxacin within the same patient group. Should the current findings prove promising, a subsequent study involving a direct comparison between ofloxacin and non-ofloxacin groups will be conducted to strengthen this finding 2. Regarding the clarification of “high initial viable infection load, evidenced by a high MI”: A high MI (Morphological Index) was not the sole criterion for patient recruitment in this study. While there is currently no universally accepted threshold in the international literature defining what constitutes a "high" MI, we based our observations on patient data from our center. In addition to elevated MI values, other factors such as persistent positivity, relapse, and re-positivity were also considered in selecting subjects for inclusion. 3. Regarding the main dose and side effects of ofloxacin: We have now included a description of the dose of ofloxacin along with its commonly reported side effects 4. Regarding the discussion section: We have revised the discussion section to make it more concise Thank you so much for your time View more View less Competing Interests none reply Respond Report a concern Ochoa MT. Peer Review Report For: Optimizing treatment of lepromatous form of leprosy using ofloxacin on top of standard multi-drug therapy in National Referral Hospital, Jakarta, Indonesia [version 1; peer review: 1 approved with reservations] . F1000Research 2025, 14 :252 ( https://doi.org/10.5256/f1000research.177837.r369473) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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