Fosfomycin for Antibiotic Prophylaxis in Men Undergoing a Transrectal Prostate Biopsy: A Systematic Review and Meta-Analysis
, Jin Seok Gu 1, Ho Seok Chung 1, Seung Il Jung 1, Dongdeuk Kwon 1,*, Myung Ha Kim 2, Jae Hung Jung 3, Mi Ah Han 4, Seung Ji Kang 5, Eu Chang Hwang 1,* and Philipp Dahm 6,7Round 1
Reviewer 1 Report
This is a well designed and conducted work. Prostate biopsy still remains the gold standard for diagnosing prostate cancer. A dispute persists regarding the access route, transrectal or transperineal, regarding the detection rate and complications. It is clear that the transrectal route may be burdened by a higher incidence of post-procedural urinary tract infections. This requires the need for antibiotic prophylaxis. This itself should be calibrated on the characteristics of the patient and not be the same for everyone. Obtaining information on the efficacy of one molecule compared to others will necessarily help in this research path.
No comment about english language
Author Response
Reviewer 1:
This is a well designed and conducted work. Prostate biopsy still remains the gold standard for diagnosing prostate cancer. A dispute persists regarding the access route, transrectal or transperineal, regarding the detection rate and complications. It is clear that the transrectal route may be burdened by a higher incidence of post-procedural urinary tract infections. This requires the need for antibiotic prophylaxis. This itself should be calibrated on the characteristics of the patient and not be the same for everyone. Obtaining information on the efficacy of one molecule compared to others will necessarily help in this research path.
Author response: Thank you very much for your valuable comments.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Dear Authors,
Prostate biopsy is still the gold standard for the diagnosis of prostate cancer, despite the advance of prostate MRI. Traditionally before prostate biopsy, an antibiotic has been given to men to prevent biopsy-related infections. In countries where fluoroquinolones are allowed as antibiotic prophylaxis, a minimum of an entire 1-day administration and targeted therapy in case of fluoroquinolone resistance is recommended. In countries with a ban on fluoroquinolones, fosfomycin is a good alternative, as is augmented prophylaxis, although no established standard combination exists to date.
Your article touches on a susceptible subject of the modern era. WHO seriously advises diminishing fluoroquinolone usage for several years according to the alarmingly increased resistance rates. Many forgotten antibiotics were reconsidered since the medical staff tried to find alternatives.
The manuscript is well-written and organized. The present study is well-conducted and designed, even though I have some minor suggestions which may improve the paper’s quality.
1. In the Introduction section, a paragraph suggests that Fosfomycin concentrates in prostatic tissue. It is helpful for this mechanism to be better explained.
2. “Two NRSs compared fosfomycin and FQ combined with FQ [36, 37].” Please rephrase this sentence.
3. In the Results section- Search. The authors mentioned 92 articles were excluded but did not mention the reason.
4. In the Conclusion section, Fosfomycin is written in uppercase and lowercase. Please correct. “Compared with FQ, fosfomycin or Fosfomycin and FQ combined had a similar prophylactic effect on UTIs after a transrectal prostate biopsy.”
5. You can add in your study the results of one the largest South Eastern European studies about the increased resistance rate for fluoroquinolones and low resistance profile for Fosfomycin: 10.3390/microorganisms8060848
No comments
Author Response
Reviewer 2:
Dear Authors,
Prostate biopsy is still the gold standard for the diagnosis of prostate cancer, despite the advance of prostate MRI. Traditionally before prostate biopsy, an antibiotic has been given to men to prevent biopsy-related infections. In countries where fluoroquinolones are allowed as antibiotic prophylaxis, a minimum of an entire 1-day administration and targeted therapy in case of fluoroquinolone resistance is recommended. In countries with a ban on fluoroquinolones, fosfomycin is a good alternative, as is augmented prophylaxis, although no established standard combination exists to date.
Your article touches on a susceptible subject of the modern era. WHO seriously advises diminishing fluoroquinolone usage for several years according to the alarmingly increased resistance rates. Many forgotten antibiotics were reconsidered since the medical staff tried to find alternatives.
The manuscript is well-written and organized. The present study is well-conducted and designed, even though I have some minor suggestions which may improve the paper’s quality.
Author response: Thank you very much for your valuable comments. We revised our manuscript according to your suggestions. Please see below.
- In the Introduction section, a paragraph suggests that Fosfomycin concentrates in prostatic tissue. It is helpful for this mechanism to be better explained.
Author response: We inserted the following sentences with new references to explain the mechanism. “Fosfomycin is an oral bactericidal agent and is a phosphonic acid derivative with a very low molecular weight. It is eliminated mainly unchanged through the kidneys, resulting in very high urinary concentrations within 2–4 hours. Therapeutic concentrations in urine are usually maintained for at least 36 hours [12]. The high urinary concentrations, combined with fosfomycin's low molecular weight, may facilitate its diffusion into surrounding tissues, such as the prostate gland [12]. While there is limited data explicitly demonstrating fosfomycin's concentration in prostate tissue [13], the drug has proven effective in treating prostatitis [14].”
- Takasaki N, Ra S, Okada S, Sakakibara T, Tonami H, Kitagawa Y, et al. Transference of antibiotics into prostatic tissues: sampling method by transurethral resection for the measurement of the concentration of antibiotics in prostatic tissue. Hinyokika Kiyo. 1986;32(7):969-75.
- Grayson ML, Macesic N, Trevillyan J, Ellis AG, Zeglinski PT, Hewitt NH, et al. Fosfomycin for Treatment of Prostatitis: New Tricks for Old Dogs. Clin Infect Dis. 2015;61(7):1141-3. DOI: 10.1093/cid/civ436
- “Two NRSs compared fosfomycin and FQ combined with FQ [36, 37].” Please rephrase this sentence.
Author response: We revised the sentence as followings “Two NRSs compared fosfomycin combined with FQ and FQ [38,39]”
- In the Results section- Search. The authors mentioned 92 articles were excluded but did not mention the reason.
Author response: We inserted the following sentences; After excluding 92 studies (The 92 studies’ titles and abstracts were irrelevant to the review question; men undergoing a transrectal prostate biopsy (population); fosfomycin (intervention); other antibiotics (comparison)), 24 full-text articles were screened,
For your information, according to the AMSTAR2 checklist (please refer to reference 40; doi: https://doi.org/10.1136/bmj.j4008), the reason for excluded studies should be provided in the full-text stage but not the title and abstract screening stage. This is why we did not provide an exclusion reason for 92 studies.
- In the Conclusion section, Fosfomycin is written in uppercase and lowercase. Please correct. “Compared with FQ, fosfomycin or Fosfomycin and FQ combined had a similar prophylactic effect on UTIs after a transrectal prostate biopsy.”
Author response: We revised the sentence as followings “Compared with FQ, fosfomycin or fosfomycin and FQ combined had a similar prophylactic effect on UTIs after a transrectal prostate biopsy.”
- You can add in your study the results of one the largest South Eastern European studies about the increased resistance rate for fluoroquinolones and low resistance profile for Fosfomycin: 10.3390/microorganisms8060848
Author response: We inserted the following sentences in the discussion section with a new citation number. “Considering the increase in FQ resistance of fecal flora and uropathogens [2, 11, 44] and high sensitivity to fosfomycin of uropathogens [44], this study provides~”
- Chibelean CB, Petca RC, Mareș C, Popescu RI, Enikő B, Mehedințu C, et al. A clinical perspective on the antimicrobial resistance spectrum of uropathogens in a Romanian male population. Microorganisms. 2020;8(6):848. DOI: 10.3390/microorganisms8060848
Author Response File: Author Response.docx
