An Aminoglycoside-Sparing Regimen with Double Beta-Lactam to Successfully Treat Granulicatella adiacens Prosthetic Aortic Valve Endocarditis—Time to Change Paradigm?

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors report a treatment of a patient with Granulicatella  adiacens endocarditis on a bioprosthetic  aortic valve who is effectively treated with early valve replacement surgery and  double beta lactam antibiotic therapy (ampicillin plus ceftriaxone).  Antibiotic sensitivity testing with strip MIC determination technology, including cross-strip testing, is done to show synergistic interaction based on the FIC-index between ampicillin and ceftriaxone or ceftibiprole.  The authors suggest that double beta lactam therapy may be synergistic and an alternative to beta lactam plus aminoglycoside therapy which is advised in various endocarditis guidelines.  This is the second case report of this observation, although the microbiologic observations are presented in more detail in this manuscript. 

 

In this case report the diagnosis of endocarditis and identification of the organism are well established. The microbiologic technique used to establish synergy is interesting but to my knowledge has not been established as a reliable method for predicting synergy by comparison to MBD checkerboard testing on time-kill studies thus perhaps even more caution should be expressed that current in the manuscript. This should be further emphasized because with early source control in this patient (valve replacement) and the ampicillin MIC of the causative isolate it is possible that this patient could have been effectively treated with ampicillin alone. 

 

Several other aspects of this paper if addressed will improve the manuscript:

1)    Abstract line 32:  no data are presented to support   any conclusion beyond the 

apparent interaction of ampicillin with the 2 cephalosporins. Thus, the results statement is not supported – no data on penicillin.

2)    A bit more information for the reader on the MBD test result system would help reader not familiar with that commercial test used.  What broth? What test inoculum?  It is likely that the system thus does not support growth of this organism thus the low MIC noted.  This may also impact your comparison MIC by BMD and the test strips. Alberti et al were very careful to be sure that test systems were equivalent including media supporting growth and inoculum.

3)    I do not think lines 260-266 add much to your discussion and could be deleted

4)    In projecting next steps especially given the unpredictability of susceptibility of this species (or Abiotrophia sp.)  you might suggest expanded in vitro and in vivo (animal models) testing of G. adiacens to confirm the reliability of the cross strip FIC-index for demonstrating synergy before blindly applying this to  treatment/

 

You demonstrated that daptomycin resistance emerges in G. adiacens on exposure of the organism to the agent.  This might be included in your manuscript to make it better known to clinicians (see Canas MA et al Antimicrob Agents Chemo 2021;65:e02442-20.  https://doi.org/10.1128/AAC.02522-20.

 

The paper has many unusual word choices, made-up words (additivity, negativzation), spelling errors (sinergy) and incomplete references.  Too many too list. It needs to be carefully edited  by a  person who is fluent in English. 

 

 

Comments on the Quality of English Language

Quality of the English language is  not adequate. This  manuscript needs to be  edited by someone fluent in the English language

Author Response

We'd like to Thank You very much for Your kind appreciations to our paper, and most off all, for Your Comments and precious suggestions.

Please see the attachment with our response

Best Regards 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

I read with interest the paper “An Aminoglycoside-Sparing Regimen with Double Beta-Lactam to Successfully Treat a Granulicatella Adiacens Prosthetic Aortic Valve Endocarditis. TIME to Change Paradigm? “The paper describes a case of G.adiacens IE on a male patients with an aortic bioprosthesis and a pacemaker, and the isolate is very well studied in a reference lab, where the synergy studies are done.

The microbiological part of the study is very well described, and the discussion is very well written. My only comment on this part of the study would be that it was difficult to see the microorganism in the photographs in Figure 2…

Regarding the efficacy of the given treatment, it is very hard to say the combination therapy was effective, as the source of infection was removed very early, with valve replacemet surgery and pacemaker removal.

Regarding the case report itself, I have two major comments:

1.       The patient’s physical examination needs to be described in more detail, including the general inspection (pale? febrile?), vital signs, respiratory (he had a dry cough, any rales?), cardiovascular, neurological, and abdominal systems. Even if those systems are normal.

2.       The indication for surgery is not clear at all, as the patient had been 2 days on IV treatment when he was taken to the operating theatre. The causative microorganism at this stage was probably not yet identified. So please address the following questions:

 What was the indication for surgery in this patient? He had no severe regurgitation, no abscess. He is a young patient, and a redo operation is no small procedure.

What sort of valve did he have implanted and what was removed?

 What were the findings at surgery?

What did valve histopathology show?

Last but not least, I have made minor suggestions and have small queries are on the file which I have attached.

Comments for author File: Comments.pdf

Comments on the Quality of English Language

English language is very good, only some very minor faults.

Author Response

We'd like to Thank You very much for Your kind appreciation to our paper, and most of all, for Your comments and precious suggestions 

Please see the attachment with our response

Best Regards

Author Response File: Author Response.pdf