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

Mufqi Handaru Priyanto; Malika Sabrina Yunifananda; Sri Linuwih SW Menaldi; Erni Juwita Nelwan; Melani Marissa

doi:10.12688/f1000research.161758.3

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Research Article

Revised

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

[version 3; peer review: 1 approved, 1 approved with reservations, 1 not approved]

Mufqi Handaru Priyanto ^1,2, Malika Sabrina Yunifananda², Sri Linuwih SW Menaldi^2,3, Erni Juwita Nelwan^3,4, Melani Marissa^2,3

Mufqi Handaru Priyanto ^1,2, Malika Sabrina Yunifananda², [...] Sri Linuwih SW Menaldi^2,3, Erni Juwita Nelwan^3,4, Melani Marissa^2,3

PUBLISHED 06 Aug 2025

Author details Author details

¹ Universitas Indonesia Hospital, Depok, West Java, Indonesia
² Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, 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

REVIEWER STATUS

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 circumstances often faces non-adherence. Ofloxacin, a fluoroquinolone, has shown promising efficacy against Mycobacterium leprae in in-vitro and in-vivo studies, therefore accelerates bacterial clearance.

Methods

This single-center 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 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.

Keywords

Lepromatous Leprosy; Ofloxacin; Multi-Drug Therapy (MDT); Bacteriological Index (BI); Morphological Index (MI); Leprosy Treatment Optimization; Indonesia

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 3; peer review: 1 approved, 1 approved with reservations, 1 not approved]. F1000Research 2025, 14:252 (https://doi.org/10.12688/f1000research.161758.3) First published: 03 Mar 2025, 14:252 (https://doi.org/10.12688/f1000research.161758.1) Latest published: 06 Aug 2025, 14:252 (https://doi.org/10.12688/f1000research.161758.3)

Revised Amendments from Version 2

This version incorporates several revisions to improve clarity, accuracy, and alignment between sections. The Abstract has been revised to clarify the role of ofloxacin in enhancing bacteriological clearance rather than reducing treatment duration, aligning it with the findings presented in the Discussion. A sentence on statistical methods has been removed from the Abstract to maintain conciseness.
The Methods section was corrected by removing a misplaced paragraph describing ofloxacin’s adverse effects, which has now been relocated to the Introduction for appropriate context. A statement was also added in the Discussion acknowledging the lack of systematic adverse event monitoring as a study limitation.
Figure 1 has been revised to clarify the inclusion criteria and explain why patients with BT/TT leprosy were excluded, despite initially being listed in the pharmacy records. Figure 2, showing the geographical distribution of patients, has been removed due to its limited relevance to the study aims.
In the Limitations section, we added details regarding the lack of a control group, retrospective design, and missing follow-up data, emphasizing the impact these factors may have on generalizability and interpretation.
Overall, these changes aim to improve transparency and strengthen the coherence of the manuscript while preserving the original findings.

See the authors' detailed response to the review by Maria T Ochoa
See the authors' detailed response to the review by Brandon L Adler

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

The most common adverse effect of ofloxacin is tendinopathy, and there may be hypersensitivity reactions, central nervous system adverse drug reactions, peripheral neuropathy, though uncommon.¹⁰

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. Each patients were given 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 criteria¹⁰; (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). 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)

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 2, 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 2. 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 2, 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 3).

Figure 3. 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 accelerates bacterial clearance and contributes to faster clinical improvement and reduces transmission.

Ofloxacin has proven effective in both paucibacillary (PB) and multibacillary (MB) leprosy, especially when combined with potent bactericidal agents like rifampicin and minocycline.¹² Though the treatment duration remains similar to standard MDT, ofloxacin-added regimens may offer enhanced efficacy, particularly in lepromatous cases.¹³

The cure rate in this study showed a consistent increase in patients achieving an MI of 0, demonstrating the effectiveness of ofloxacin in reducing viable bacterial load. This result is similar to other study evaluating OMDT in non-endemic area that showed a high cure rate and tolerability.⁵ Additionally, studies combining ofloxacin with rifampicin and minocycline reported 2-year cure ranging from 93.1% to 99%.^14,15 A long-term follow-up trial also recorded relapse in only 1 of 58 patients over an average of 10.8 years.¹⁶

Another advantage of ofloxacin is its rapid action compared to some other drugs traditionally used in leprosy treatment. Studies have shown that it can quickly reduce the BI, which can be crucial in treating severe or resistant cases of leprosy.¹⁷ Our study observed significant MI reduction following its addition, with the median MI reaching 0 after six months. Statistical analysis confirmed significant differences 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). Previous studies support this, showing daily ofloxacin in lepromatous patients were experiencing rapid MI decline and >99.99% bacterial killing by day 28.¹⁸ Another study found no resumption of bacterial growth even 18 months post-treatment.¹⁹ Compared to WHO MDT, MI reduction was more significant with ROM (rifampicin, ofloxacin and minocycline) regimen: 79.97% of WHO MDT and 94.83% of ROM.²⁰ In addition to MI, our study also found significant reductions in the bacterial index (BI) across visits (p = 0.007), with pairwise differences noted at three (p = 0.039), six (p = 0.003), nine (p = 0.006), and 12 months (p = 0.004). These findings emphasize the importance of early ofloxacin addition in cases with high bacterial loads, enhancing bacterial clearance and reducing relapse risk.⁷

Early use of ofloxacin, especially under the right clinical criteria, may shorten treatment, boost adherence, and reduce discontinuation. In our cohort, WHO MDT had been administered for a median of nine months (range 1–31) before ofloxacin was introduced. However, waiting this long may not be necessary—patients with high MI and BI may benefit from earlier ofloxacin initiation.

Ofloxacin also contributes to resistance prevention when combined with other antibiotics such as rifampicin, clofazimine, and dapsone, as it offers broader coverage and improves outcomes while reducing resistance risk.²¹ Notably, studies have shown that ROM regimens are better tolerated than MDT-WHO, improving adherence.²⁰

Its utility is especially crucial in MB leprosy with higher MI and bacterial load.²² Ofloxacin and minocycline have shown stronger bactericidal effects than dapsone and clofazimine in both animal models and clinical trial.²³ This is vital in special cases like dapsone hypersensitivity syndrome (DHS).²⁴ Effective bacterial clearance in such cases is crucial, given that high BI is a known risk factor for grade 2 disability.²⁵

Finally, in cases of drug-resistant leprosy, ofloxacin has been used as an alternative when standard drugs fail.⁵ As leprosy cases become increasingly concentrated in specific regions, newer antibiotics like ofloxacin will play an increasing role in global leprosy control, preventing complications and disabilities.²⁰

This is the first Indonesian study evaluating ofloxacin’s addition to WHO MDT in lepromatous leprosy. Its use is recommended in cases with: (1) a high initial MI; (2) persistently positive MI, typically after ≥6 months of MDT; (3) re-positivity of MI; and (4) relapse, diagnosed based on criteria by Linder et al.⁸ In Indonesia, ofloxacin is the only second-line drug for leprosy covered by the national health insurance, limited to referral hospital and for one week’s use. Patient must either self-fund or return weekly to continue therapy, highlighting the need for improved access and policy reform, especially for those in rural areas.

We acknowledge that this study has limitations. Firstly, being a being a retrospective study, it inherently carries the potential for biases that are simply part of this design. This also meant that some aspects, such as comprehensive patient follow-up data and a systematic evaluation of drug tolerance and adverse reactions, were challenging to capture adequately from existing records. Secondly, the absence of a concurrent control group receiving standard multi-drug therapy (MDT) without ofloxacin restricts direct comparative analysis of bacteriological and morphological indices. This design choice was influenced by ethical considerations at our national referral center, which primarily manages challenging cases. Thirdly, as a single-center study, the generalizability of our findings may be limited to other populations or healthcare settings. 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

The addition of ofloxacin to the standard WHO MDT regimen in lepromatous leprosy resulted in a significant and consistent reduction in the morphological index (MI) and bacterial index (BI), with the median MI reaching 0 after six months of treatment. These findings support the potent bactericidal activity of ofloxacin and its potential to accelerate bacterial clearance, enhance clinical outcomes, and reduce transmission and relapse risk.

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.

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Version 3

VERSION 3 PUBLISHED 03 Mar 2025

Author details Author details

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 (3)

version 3

Revised

Published: 06 Aug 2025, 14:252

https://doi.org/10.12688/f1000research.161758.3

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Published: 28 Apr 2025, 14:252

https://doi.org/10.12688/f1000research.161758.2

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Published: 03 Mar 2025, 14:252

https://doi.org/10.12688/f1000research.161758.1

© 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.

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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 3; peer review: 1 approved, 1 approved with reservations, 1 not approved]. F1000Research 2025, 14:252 (https://doi.org/10.12688/f1000research.161758.3)

NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.

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ApprovedThe 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 approvedFundamental flaws in the paper seriously undermine the findings and conclusions

Version 3

VERSION 3

PUBLISHED 06 Aug 2025

Revised

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Reviewer Report 03 Sep 2025

Fifa Argentina, Universitas Sriwijaya, Palembang, South Sumatra, Indonesia

Approved

https://doi.org/10.5256/f1000research.186135.r407739

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 ... Continue reading

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.

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Version 2

VERSION 2

PUBLISHED 28 Apr 2025

Revised

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Reviewer Report 13 Jun 2025

Brandon L Adler, Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

Not Approved

https://doi.org/10.5256/f1000research.180812.r384857

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.

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Author Response 18 Aug 2025

Mufqi Handaru Priyanto, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia

18 Aug 2025

Author Response
Thank you for this study evaluating the impact of addition of ofloxacin to MDT for lepromatous leprosy, conducted in a single center.
1. “At our center, slit-skin smear
... Continue reading
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.
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.
Competing Interests: No competing interests were disclosed. Close
Report a concern
Respond or Comment

COMMENTS ON THIS REPORT

Author Response 18 Aug 2025

Mufqi Handaru Priyanto, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia

18 Aug 2025

Author Response
Thank you for this study evaluating the impact of addition of ofloxacin to MDT for lepromatous leprosy, conducted in a single center.
1. “At our center, slit-skin smear
... Continue reading
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.
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.
Competing Interests: No competing interests were disclosed. Close
Report a concern

Version 1

VERSION 1

PUBLISHED 03 Mar 2025

Views

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

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 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.

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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
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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
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Version 3

VERSION 3 PUBLISHED 03 Mar 2025

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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

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Reviewer Report

4 Views

03 Sep 2025 | for Version 3

Fifa Argentina, Universitas Sriwijaya, Palembang, South Sumatra, Indonesia

4 Views Cite this report Responses(0)

Approved

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.

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Reviewer Report

26 Views

13 Jun 2025 | for Version 2

Brandon L Adler, Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

26 Views Cite this report Responses(1)

Not Approved

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

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.

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Reviewer Report

42 Views

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

42 Views Cite this report Responses(1)

Approved With Reservations

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

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

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

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

Abstract

Background

Methods

Findings

Interpretation

Keywords

Revised Amendments from Version 2

Introduction

Methods

Study design

Participants

Figure 1. Selection of participants for the study.

Procedures

Outcomes

Statistical analysis

Results

Sociodemographic and disease characteristics

Table 1. Sociodemographic and disease characteristics of the subjects.

Morphological index (MI) clearance on MDT combined with ofloxacin

Figure 2. Changes in absolute morphological (left) and bacterial (right) indices before and after ofloxacin addition.

Bacterial index (BI) clearance on MDT combined with ofloxacin

Proportion of patients achieving MI 0

Figure 3. Proportion of patients achieving absolute morphological index of 0 before and after the addition of ofloxacin.

Discussion

Conclusion

Ethics and consent

Contributors

Data availability

Underlying data

Software availability

References

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