Potency of commonly retailed antibiotics in pharmacies found in Adama, Oromia regional state, Ethiopia

Demelash Demissie; Teshome Geremew; Adinew Zewdu Chernet; Musa Mohammed Ali

doi:10.1371/journal.pone.0253971

Peer Review History

Original SubmissionFebruary 15, 2021
23 Apr 2021 Decision Letter - Praveen Rishi, Editor PONE-D-21-05088 Potency of commonly retailed antibiotics in pharmacies found in Adama, Oromia regional state, Ethiopia PLOS ONE Dear Dr. Ali, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Jun 07 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information. Moreover, please include more details on how the questionnaire was pre-tested, and whether it was validated. Moreover, please clarify how each variable was defined and categorised. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: No Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: I Don't Know ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No Reviewer #2: No ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: In this submitted manuscript authors claimed that about 40% of antibiotics tested in the present study were not potent and the potency of antibiotics varies based on the source of the country. Authors also claimed that most of azithromycin were not potent while all ceftriaxone were potent. Author (s) mentioned that the physicochemical condition in the pharmacy setup significantly associated with the potency of antibiotics.Manuscript is not technically sound due to poor presentation and so it is very difficult to understand what kind of message to give the author (s) in the present MS. However, there are following points that need to be addressed :1. What could be the scientific reason, reduction in potency of antibiotic.?2. Does variation of API ( Source of API) in the antibiotics preparations responsible for antibiotic potency.3. Does the pharmacy set up awareness of this type of loss in the potency of antibiotics? Reviewer #2: Comments This study about “Potency of commonly retailed antibiotics in pharmacies found in Adama, Oromia regional state, Ethiopia -” provides interesting data but has many shortcomings. These points should be addressed. My major comments are as follows. 1.The manuscript is not written so well and therefore, it is difficult to understand what authors want to say. 2.Language of the manuscript needs to be improved thoroughly. Some points, words or sentences have been highlighted in the manuscript and corrections should be made throughout the manuscript thoroughly. 3.On page number 13, E. coli must be italicized in table 3. 4. “To obtain 10 μg of amoxicillin disc, 500 mg of amoxicillin tablet was dissolved in 250 ml of phosphate buffer and 5 μm of dissolved stock antibiotic was impregnated on the 6 mm sized disc. To obtain 5 μg of ciprofloxacin disc, 500mg of ciprofloxacin tablet was dissolved in 500ml of distilled water and 5 μm of dissolved stock antibiotic was impregnated on the 6 mm sized disc. To obtain 30 μg of ceftriaxone, 1000mg of injectable ceftriaxone was dissolved in 166.7ml of distilled water and 5 μm of dissolved stock antibiotic was impregnated on the 6 mm sized disc. To obtain 15 μg of azithromycin, 500mg of azithromycin the tablet was dissolved in a 166.7 ml of 95% ethanol with a broth media and 5 μm of dissolved stock antibiotic was impregnated on the 6 mm sized disc.” Authors have used different volumes of different solvents and different amounts of antibiotics, justify. 5.“5 μm of dissolved stock antibiotic was impregnated on the 6 mm sized disc”. What does “5 μm” mean? How authors confirmed/checked that 5 μm was impregnated on disc? 6.Present work describe the potency of antibiotics. In Table 4, what factors were considered to define/calculate potency of antibiotics on the basis of country? 7.Which factors define the pass and fail percentage of any antibiotic in Table 4 and 5? ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes:** NA Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0253971.r001
Revision 1
3 May 2021 Author Response Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: No Reviewer #2: Partly ________________________________________ 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: I Don't Know ________________________________________ 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ________________________________________ 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No Reviewer #2: No ________________________________________ 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: In this submitted manuscript authors claimed that about 40% of antibiotics tested in the present study were not potent and the potency of antibiotics varies based on the source of the country. Authors also claimed that most of azithromycin were not potent while all ceftriaxone were potent. Author (s) mentioned that the physicochemical condition in the pharmacy setup significantly associated with the potency of antibiotics. Manuscript is not technically sound due to poor presentation and so it is very difficult to understand what kind of message to give the author (s) in the present MS. Response: Thank you for your valuable comments. • In order to address the technical issue of the manuscript, we have included the following information in the method section: categories of antibiotics tested and their form (in the study design and population), Recommended storage condition of evaluated antibiotics, antibiotic disc preparation heading with detail description, antimicrobial susceptibility testing heading with detail description, pass criteria heading with detail description. We have also included details of what we did to maintain the quality of the data under Data quality control. All these are shown in the manuscript with track change. However, there are following points that need to be addressed :1. What could be the scientific reason, reduction in potency of antibiotic.?2. Does variation of API ( Source of API) in the antibiotics preparations responsible for antibiotic potency.3. Does the pharmacy set up awareness of this type of loss in the potency of antibiotics? Response: • Yes, most of the antibiotics tested did not pass the potency test; several factors can be the reason for the failure. In addition to factors that are significantly associated with the potency of the antibiotics in the current study, other factors such as substandard, counterfeit, laboratory methods used can also affect the potency of antibiotics. There are also possibilities of illegal antibiotics in pharmacies. We have mentioned these reasons in the middle and as the end of the discussion section. • The pharmacies are of about the ineffectiveness of antibiotics indirectly from customers (there is no improvement despite antibiotic intake). We have communicated the finding of this study to concerned bodies. Reviewer #2: Comments This study about “Potency of commonly retailed antibiotics in pharmacies found in Adama, Oromia regional state, Ethiopia -” provides interesting data but has many shortcomings. These points should be addressed. My major comments are as follows. 1. The manuscript is not written so well and therefore, it is difficult to understand what authors want to say. Response: Thank you for your constructive comments. • We agree with comment; we have revised the manuscript as shown in the track change. 2.Language of the manuscript needs to be improved thoroughly. Some points, words or sentences have been highlighted in the manuscript and corrections should be made throughout the manuscript Response: • We agree with comment; we have revised the languages as shown in the track change. 3.On page number 13, E. coli must be italicized in table 3. Response: We italicized as suggested. 4. “To obtain 10 μg of amoxicillin disc, 500 mg of amoxicillin tablet was dissolved in 250 ml of phosphate buffer and 5 μm of dissolved stock antibiotic was impregnated on the 6 mm sized disc. To obtain 5 μg of ciprofloxacin disc, 500mg of ciprofloxacin tablet was dissolved in 500ml of distilled water and 5 μm of dissolved stock antibiotic was impregnated on the 6 mm sized disc. To obtain 30 μg of ceftriaxone, 1000mg of injectable ceftriaxone was dissolved in 166.7ml of distilled water and 5 μm of dissolved stock antibiotic was impregnated on the 6 mm sized disc. To obtain 15 μg of azithromycin, 500mg of azithromycin the tablet was dissolved in a 166.7 ml of 95% ethanol with a broth media and 5 μm of dissolved stock antibiotic was impregnated on the 6 mm sized disc.” Authors have used different volumes of different solvents and different amounts of antibiotics, justify. Response: For preparation of antibiotics, we have followed CLSI guideline (CLSI guideline M_100S26, 2016, 26 ed, Table 6A, page 192). Preparation procedure is attached as supplement file. 5.“5 μm of dissolved stock antibiotic was impregnated on the 6 mm sized disc”. What does “5 μm” mean? How authors confirmed/checked that 5 μm was impregnated on disc? Response: We agree with the comment and corrected as 5 μL. 6.Present work describe the potency of antibiotics. In Table 4, what factors were considered to define/calculate potency of antibiotics on the basis of country? Response: We agree with the comment and included ‘pass’ and ‘fail’ criteria set by CLSI in the method section as shown in the track change. 7.Which factors define the pass and fail percentage of any antibiotic in Table 4 and 5? Response: We agree with the comment and included ‘pass’ and ‘fail’ criteria set by CLSI in the method section. Attachments Attachment Submitted filename: Response to reviewers comments.docx https://doi.org/10.1371/journal.pone.0253971.r002
17 Jun 2021 Decision Letter - Praveen Rishi, Editor Potency of commonly retailed antibiotics in pharmacies found in Adama, Oromia regional state, Ethiopia PONE-D-21-05088R1 Dear Ali, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Praveen Rishi, Ph.D., FAMI, FABMS Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: (No Response) Reviewer #2: (No Response) ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't Know Reviewer #2: N/A ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: No Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Still the author must improve the language of the MS rigorously. Still it is very difficult to understand the MS due to poor presentation. Reviewer #2: In line 147; “The uncertainty measurement for amoxicillin, ciprofloxacin, azithromycin, and ceftriaxone with a 95% CI were 17-19 mm, 31-32 mm, 21-24 mm, and 31-33 mm respectively.” What does “CI” refer to? ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes:** Satish K Pandey Reviewer #2: No https://doi.org/10.1371/journal.pone.0253971.r003
Formally Accepted
21 Jun 2021 Acceptance Letter - Praveen Rishi, Editor PONE-D-21-05088R1 Potency of commonly retailed antibiotics in pharmacies found in Adama, Oromia regional state, Ethiopia Dear Dr. Ali: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Prof. Praveen Rishi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0253971.r004

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