The Molecular Characterization of Nosocomial Carbapenem-Resistant Klebsiella pneumoniae Co-Harboring blaNDM and blaOXA-48 in Jeddah
Round 1
Reviewer 1 Report
The manuscript is well written and it is an important report on Carbapenem-Resistant Klebsiella pneumoniae harboring blaNDM and blaOXA-48 in Jeddah. Some points to be considered for improvement:
1- I suggest changing co-harboring in the title to ‘harbouring’’ as only a small percentage co-harboured both genes.
2- Line 142: ‘’The susceptibility tests for several antimicrobial agents were performed, including imipenem, meropenem, ertapenem, ampicillin, amoxicillin/clavulanic acid, ceftazidime, cefepime, amikacin, gentamicin, ciprofloxacin, levofloxacin, piperacillin/tazobactam, trimethoprim/sulfamethoxazole, colistin and tigecycline.’ Do you mean using Vitek, or did you do it manually using the disc diffusion method?, it needs clarification.
3- Revise this sentence ‘’First, the DNA template of all samples was prepared and extracted using DNA was isolated from the…..’’
4- Revise the writing names of genes in Table 1
5- add a comma before respectively, throughout the manuscript.
6- A correlation between the presence of genes and MIC should be done
7- Conclusion at the end of the discussion section should be added.
Author Response
Thank you for your valuable comments
1- the word harbouring will be added
2- yes all AST panels were done by Vitek.
3-4 will be revised
5- will be added
6-7 will be revised
Many thanks for your comments
Reviewer 2 Report
This easy-to-read manuscript by Alhazmi, et. al. The study aimed to determine the molecular epidemiology of Carbapenem-resistant Klebsiella pneumoniae (CRKP) and identify the most common carbapenemase genes (blaNDM, blaOXA-48, blaKPC, blaIMP and blaVIM) in isolates collected from clinical samples in Jeddah, Saudia Arabia. One of the major finding was that identification of CRKP co-harboring both blaNDM and blaOXA-48. Due to their high prevalence of carbapenem resistance, such isolates may pose a threat to healthcare systems.
Here are comments for improvement of the manuscript:
Q1) Whether patient’s consents were taken for the study??
Q2) Rewrite line no. 156 to 158 its confusing “First, the DNA template of all samples was prepared and extracted using DNA was isolated from the overnight cultures that are cultivated
from the isolates stored in -80 °C for multiplex-PCR analysis.”
Q3) Table 3.1 can be shifted to supplementary files.
Q4) Where is table 3.2 mentioned online number 169?
Q5) In result section: 3.1 The demographic characteristics of patients with CRKP infections : As author said that this study will eventually enable the health care facilities to improve their policies of the infection control. It would be interesting to know the ethnicity of the patient.
Q6) Figure 4.1-line no. 208 and Figure 4.2 -line no. 210, Figure 4.4 -line no. 240, can be shifted to supplementary
Author Response
Thank you for your valuable comments
-of course
-Revised and re-written
- deleted
-all added to a supplementary file
-I agree it would be interesting however, it is difficult to obtain these data in the current time
comments revised and written in the manuscript
Reviewer 3 Report
Alhazmi et al. have provided a report on the distribution of frequently detected carbapenemases in K. pneumoniae isolates from a Saudi Arabian military hospital. Before publication can be considered, I have a number of suggestions on how to further improve the manuscript.
1. The title of the article is misleading. K. pneumoniae isolates co-harboring genes encoding NDM-type and blaOxa-48-type beta-lactamases were not subjected to a deeper molecular characterization. The co-detection was just a result of the PCR screening for common carbapenemases in the strains.
2. Introduction, second paragraph: A reference of the Ambler classification, to which the authors refer in this paragraph, should be presented.
3. Introduction, lines 49-50: It should be made clear that the quoted enzymes are just examples of carbapenemases of the mentioned Ambler classes.
4. Introduction, lines 53-54: It should be made clear that the K. pneumoniae carbapenemase is just an example of carbapenemases potentially occurring in K. pneumoniae.
5. Materials and methods, line 121: It seem there is a part of the sentence missing at the beginning.
6. Introduction, line 146: If the authors have indeed tested colistin susceptibility just based on the VITEK-approach (and not confirmed by microbroth dilution), they should at least discuss the accuracy limitations of this method in a limitations paragraph of the discussion.
7. Results, second paragraph: In some of the mentioned sample materials acquired from primary non-sterile sample materials, K. pneumoniae both can cause infection but also can persist just as a clinically harmless colonizer. Typically, this decision can only be made clinically. So, if the authors have clinical hints whether or not the isolates caused infections or just harmlessly co-existed, this information would be worth presenting. If such information is not available, this should be provided as a limitation in the limitations section of the discussion.
8. Results, second paragraph: The authors generally postulate a high risk due to carbapenem-resistant K. pneumoniae in various clinical sample materials of their patients. To truly assess the quantitative dimension of this risk, the total numbers of clinical K. pneumoniae isolates (comprising both susceptible and resistant strains) should be provided as denominators. By doing so, proportions of carbapenem-resistant isolates could be shown. This would be highly informative. If such information is not available, this should be provided as a limitation in the limitations section of the discussion.
9. Results, sub-heading 3.4.: It is unclear to me what exactly has been correlated here with the abundance of carbapenemase genes? Just phenotypical carbapenem resistance? Or the total resistance profile? What shall really be shown with this subheading? If it is not really necessary for the demonstration of the authors’ intention (for which an explanation should be provided), I recommend that this sub-heading is removed as superfluous from the manuscript.
10. Results, sub-headings 3.4 and 3.5.: When referring to the measured correlations, the authors use quite poor language style by repeatedly using the same sentence structure. Also, this repetition is redundant to the respective tables. I suggest just referring to the tables and verbally describing only the most important findings. This will also considerably shorten the respective paragraphs.
11. Discussion, lines 304-306: Do the authors really feel that age is an independent risk factor for carrying carbapenem-resistant K. pneumoniae? Do they have checked for confounding by health-care association? This would be the minimum requirement to pose such a claim. Otherwise, the authors should weaken their statement.
12. Discussion, 4th paragraph: The authors’ focus on minor phenotypical resistance differences in the carbapenemase-positive strains is hard to understand. It is well known from the literature that carbapenemase-carriage is an independent predictor for poor outcomes in case of carbapenem-based therapy. So, the authors should better explain why this seems (clinically?) so important to them.
13. Lines 340-342: The breaks in this sentence make it nearly impossible to read it in one piece.
14. A limitation paragraph is missing at the end of discussion, although the study has indeed a number of limitations as addressed in the points above.
15. Minor comment: The whole manuscript should be subjected to language proof-reading by a native speaker either by the authors or by the journal. Although the intended contents are usually obvious, typing, Grammar and syntax errors partially make the manuscript difficult to read.
Author Response
thank you for your comments
Most of the comments were revised and written in the manuscript that is attached and sent
