Referee 1 Reviewer`s report Title: Mycoplasma hominis necrotizing

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Referee 1
Reviewer's report
Title: Mycoplasma hominis necrotizing pleuropneumonia in an immunocompetent adolescent
Version: 2 Date: 19 April 2010
Reviewer: Thomas Atkinson
Reviewer's report:
Summary: This manuscript documents a severe necrotizing pneumonia in a previously healthy
adolescent due to Mycoplasma hominis. While the case is dramatic and potentially interesting,
the authors’ response to the previous critique is inadequate for the following reasons:
1. Although the version of the revised manuscript that I received does not include the
title and author page, these are noted in the authors’ response letter. The term
“immunocompetent” is inappropriate since this is something that must be
demonstrated rigorously, while only a limited evaluation has been performed
(Negative HIV testing, normal immunoglobulins). Curiously, none of the
immunologic testing that has been performed is actually mentioned in the text.
We agree with the reviewer. We used the term “immunocompetent” since the patient
was in perfect health at to this episode of pneumonia and because all the results of
the test searching the most common causes of immunosupression were negative or
normal [Elisa HIV Test, C3 C4, Immunoglobulin’s levels (IgG, IgG1, IgG2, IgG3
and IgG4, IgA and IgM)] and we had thought that it would not be necessary to
specify all the tests done in the article.
As the reviewer suggested, in this new version of the manuscript we suppressed the
term “immunocompetent” in the title and in the discussion section. We replaced
“immunocompetent” by “previously healthy” adolescent.
2. The most important pieces of diagnostic testing cited are the PCR and TaqMan assays,
which continue to be inadequately described – no details regarding sensitivity and
specificity testing are provided. Unpublished tests of this type are unacceptable to
establish diagnosis.
We agree with the reviewer. The data regarding the TaqMan PCR is now accepted for
publication:
Pascual A, Jaton-Ogay K, Ninet B., Bille J., Greub G.: New Diagnostic Real-Time
PCR for Specific Detection of Mycoplasma hominis DNA. Int J Microbiol 2010,
2010: 317512.
doi:10.1155/2010/317512
3. There continue to be numerous grammatical problems and unacceptable inaccuracies –
for example in the first paragraph of the Background section, the authors state that the
M. hominis genome contains 256 genes, which would be far smaller than that of M.
genitalium, the mycoplasma with the smallest genome, which has about 470 genes.
This statement also does not agree with information included in the abstract of the
associated reference, which states that M. hominis has 537 coding sequences. The
number of 256 genes apparently refers to a discussion of a purely theoretical minimal
genome in that reference.
We agree with the reviewer and it was specified in the previous text of the
manuscruptipt that number of 256 genes refered to a theoretical minimal genome.
As the reviewer propose we suppressed this phrase in the introduction section of this
new version of the manuscript.
We modified it by: Page 3, line 39: “A recent analysis of the M. hominis genome
sequence revealed that it is the second smallest genome among self-replicating free
living organisms with a predicted genome of 537 coding genes”
Referee 2
Reviewer's report
Title: Mycoplasma hominis necrotizing pleuropneumonia in an
immunocompetent adolescent
Version: 2 Date: 27 March 2010
Reviewer: Ran Nir-Paz
Reviewer's report:
Major Compulsory Revisions
1. M. hominis specific Taq man primers can detect some other mycoplasma species
according to the primers provided. Therefore, authors need to provide reference to
sequencing data and to submit the sequencing data to the NCBI database. Additionally
they need to provide information regarding homology to known sequences.
We agree with the reviewer. The data regarding the TaqMan PCR is now accepted for
publication:
Pascual A, Jaton-Ogay K, Ninet B., Bille J., Greub G.: New Diagnostic Real-Time
PCR for Specific Detection of Mycoplasma hominis DNA. Int J Microbiol 2010,
2010: 317512.
doi:10.1155/2010/317512
2. Chest tube insertion by itself is not a surgery (page 5). However if additional surgical
procedures were done (pericardiectomy with window, decortication of lung?) then please
specify the exact procedure and avoid the use of the non informative term “surgery”.
We agree with the reviewer. The exact procedure done was specified.
The new phrase in this modified version of the manuscript is:
Page 5, line 95: “Due to her worsening respiratory and hemodynamic condition, the
pericardial and pleural effusions were evacuated by pericadiectomy with window and
pleural drainage by chest tube insertion. Apart from supplemental oxygen, she didn’t
need any further respiratory support”.
3. Case presentation is still lacking important information. At the end it is stated that the
patient was admitted for 19 days to the ICU. However, no clinical information on the case
presentation can hint for instability that would require ICU admission. Thus: did the patient
had respiratory instability? Problems with oxygenation? Tachypnea? Was she ventilated? If
yes for how long? Did she have fever? I assume that clinical presentation in this case was
dramatic and impressive which might explain the type and extension of initial antibiotic
treatment. This is not reflected in the current presentation.
We agree with the reviewer. We added some important and relevant clinical data about the
presentation of this M hominis pneumonia. The case was dramatic and she was admitted to the
ICU because she needed oxygen administration but not mechanical ventilation. The stay in
the ICU was extended up to 7 days due to the clinical instability after the pericardiotomy and
pleural drainage. She also had high fever as described in the manuscript.
We modify the text of the manuscript in order to clarify all these important topics.
Page 4, line 59: “A previously healthy 15-year-old sexually active female was
admitted to our hospital because of dyspnoea, fever and right thoracic pain.”
Page 4, line 69: “The high fever however persisted, therefore a chest CT scan was
done on the seventh day of antibiotic treatment, showing a bilateral necrotizing
pneumonia as well as a bilateral pleural effusion.”
Page 5, line 95: “Due to her worsening respiratory and hemodynamic condition, the
pericardial and pleural effusions were evacuated by pericadiectomy with window and
pleural drainage by chest tube insertion. Apart from supplemental oxygen, she didn’t
need any further respiratory support”.
Page 5, line 105: “This treatment was associated with clinical and biological
improvement and the patient could be discharged from the hospital on day 19.”
4. Table 1 should be part of the manuscript and not as supplemental material. I would
also encourage the authors to discuss the previous case reports in more than 1 sentence
in the discussion. The power of a single case report like this comes from the literature
review and the critical review of the common and less common features in between
the cases.
We agree with reviewer. We amended the manuscript to discuss the previous cases
reported in the literature. We also keep the table 1 as supplemental material, as
required in the previous revision of the manuscript.
In the present version of the manuscript we modify the text of the manuscript as
follows:
Page6, line 122: The 11 previously reported cases of M. hominis pneumonia in
immunocompetent patients are summarized in table 1. [1-5]
Six cases occurred in patients with pre-existing co-morbidities (4 traumas or surgery, 1
subarachnoid haemorrhage and 1 oesophageal carcinoma with tracheoesophageal
fistula and septic shock). One case occurred in a pregnant woman, and the other four
cases occurred in patients with no known predisposing conditions.
All the five patients who received an adequate antibiotic against M. hominis
completely recovered. Among those receiving an inadequate antibiotic therapy against
M. hominis, four died and two recovered suggesting that M. hominis infection
aggravate the pre-existing conditions and may lead to death.
Minor revisions:
1. Page 3 - I would not use “rarely”. Uncommonly will be more appropriate for this
pathogen. As is correctly stated later on the page.
Page3, line42: the term “rarely” was changed by “uncommonly” as proposed by the
reviewer.
2. Plenty of typos. For example authors are not consistent on the way they write M.
hominis throughout the text.
As proposed, M. hominis is now written in the same way throughout the manuscript.
3. The sentence “Mycoplasma hominis could be an underestimated cause of severe
pneumonia in immunocompetent children,…” should be deleted.
Adolescents are not children especially if sexual intercourse is major risk for colonization.
Additionally this sentence is too speculative by its’ nature.
We agree and modified the manuscript: “Mycoplasma hominis could be an
underestimated cause of severe pneumonia in immunocompetent children,…” was deleted
and replaced by the following one:
Page7, line 141: “M. hominis could be an underestimated cause of severe pneumonia in
previously healthy patients, particularly when other common etiological agents have been
ruled out in those not responding to standard therapy.”
4. Page 7 top line NCCLS is now CLSI – please correct. Additionally the CLSI have
published guidelines for mycoplasma breakpoint and that should be quoted.
Page7, line 148: We agree and amended the manuscript, the abbreviation NCCLS was
changed by CLSI. The existing bibliography about M hominis breakpoint has been quoted.
Unfortunately there’s no current guidelines published by CLSI.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
'I declare that I have no competing interests
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