Author's response to reviewer (Dr. Gordan)
Title: Retrospective Risk Factors Analysis of Extended-Spectrum
β-Lactamase-Producing Enterobacter cloacae Bloodstream Infections in Central
Taiwan
Authors: Chang-Hua Chen, Chieh-Chen Huang (cchuang@dragon.nchu.edu.tw)
Version: 2
Date: 25 April ,2013
Dear Dr. Gordan,
The authors thank your constructive comments. It is our pleasure to submit a
revised manuscript that has been amended in light of the reviewer’ feedback. This
manuscript had been edited by native English-speaking experts of UBM Medica Asia
Pte Ltd at first, and the revised version of this manuscript has been edited and
approved by professional editors of American Journal Experts..
We appreciated your comments, and our answers are as followings
#1
Question:
The authors identify 56 infections as nosocomially acquired, but do not describe how
this is defined. It is unclear if the remaining infections (patients referred from a local
hospital) are community acquired or were acquired in the referring hospital. This is
important as the disease severity may be affected by
co-morbidity, which is likely to be higher for a nosocomial infection.
Answer:
In the past , the Centers for Disease Control and Prevention (CDC) surveillance
definitions (Garner JS, 1988) include only nosocomial infection (NI) ; infections that
are not nosocomial are considered to be community acquired by default. [ reference :
Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for
nosocomial infections, 1988. Am J Infect Control. 1988;16:128-40 , PMID:284189].
Bu the definition cannot cover all the clinical condition . Many scholars harbour
suscicious ( such as Friedma ND, et al . Health Care–Associated Bloodstream
Infections in Adults: A Reason To Change the Accepted Definition of
Community-Acquired Infections . Ann Intern Med. 2002;137:791-797 ) . In Mayhall’s
textbook, a HAI was defined as a localized or systemic condition that ( 1 ) results
from an adverse reaction to the presence of an infectious agent(s) or its toxin(s), ( 2 )
that occurs during a hospital admission, ( 3 ) for which there is no evidence the
infection was present or incubating at a admission, and ( 4 ) meets body site-speci c
criteria. [ reference : Horan TC, Gaynes RP. Surveillance of nosocomial infections. In:
Mayhall CG, editor. Hospital epidemiology and infection control. 3rd ed. Philadelphia:
Lippincott Williams & Wilkins, 2004. p.1659-702.]. And, Horan TC had revised the
definition in 2008 [ references : Horan TC , Andrus M, Dudeck MA. CDC/NHSN
surveillance definition of health care-associated infection and criteria for specific
types of infections in the acute care setting . Am J Infect Control, 2008 ;36:309–332] .
Last month , CDC/NHSN had minor revised the definition at the document of
Protocol Corrections, Clarification, and Additions.
In this study , data were collected from medical charts on standardized forms for
all patients. HAIs were defined according to CDC criteria [ Horan TC , Andrus M,
Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection
and criteria for specific types of infections in the acute care setting . Am J Infect
Control, 2008; 36 : 309–332 ]The enrolled criteria are all conditions of a CDC/NHSN
site specific infection criterion were first present together on or after the 3 rd hospital
day (day of hospital admission is day 1). And those conditions of the community
acquired or acquired in the referring ospitals are not enrolled into HAI.
We exchnage the “nosocomial infection” into “health care-associated infection”
in order to avoid confusion..
#2
Question
I would also be interested to know how many ESBL+ve infections were treated
with cefipime and the MICS for these isolates as there is evidence to suggest
that mortality is higher in cefipime treated patients, even for apparently
susceptible isolates (Lee et al, CID 56:488).
Answer:
In Lee’s study showed efepime definitive therapy is inferior to carbapenem
therapy in treating patients with so-called cefepime-susceptible ESBL-producer
bacteremia. Concerning the antibiotic sensitivity testing (AST), beta-lactams
(including cefepime ), aminoglycosides , fluoroquinolones and
trimethoprim-sulfamethoxazole were performed with the disk diffusion method (BBL,
Sensi-Disc; Becton Dickinson, Cockeysville, MD), according to the guidelines of the
Clinical and Laboratory Standards Institute (CLSI) .
Becasue of the prescription-habit of physicians and the few Enterobacter cloacae
isolates with resistance to cefepime, only one patient was treated with cefipime alone
( cefepime monotherapy ) among 20 patients with ESBL+ Enterobacter cloacae
infections in this study. Our data is comtabible to the Lee’s findings.
#3
Question
The interpretation of the molecular analysis is somewhat confusing. The authors have
performed PFGE on 13 isolates but I am unclear as to why these isolates were chosen.
Since 10 were from ESBL positive patients who died, the conclusion that clone A is
associated with higher mortality cannot be justified as they do not know which clone
was present in the survivors.
Answer:
The increased prevalence of Enterobacter cloacae(E. cloacae) and the high
assocaited mortality rate of E. cloacae infection and high IntI1-carrying rate (70%)
created a great need for laboratory testing methods , so we'd motivated to performe
the pulsed-field gel electrophoresis(PFGE). PFGE is auxiliary investigation to
outbreak of some-kind of E. cloacae isolates. Theoretically all of 70 isoaltes needed to
be studied. And, we want to figure our exitance of outbreak and the association
between the high assocaited mortality rate and ESBL-positive E. cloacae. Besides, we
used a Bio-Rad CHEF DRIII (Bio-Rad Laboratories), and each gel posses only 15
wells . Excluding two wells for markers, only 13 wells remain. We selected 13
samples because of the main motivation (for exitance of outbreak and the
association between the high assocaited mortality rate and ESBL-positive E.
cloacae) ,and the limitation of the facility with manpower .Ten ESBL-positive
isolates from expired patients and one each of an ESBL-positive isolate from a
survivor, an ESBL-negative isolate from an expired patient and an ESBL-negative
from a survivor . So, all 13 strains were typed. There was no significant evidence of
clonal dissemination during the three years of the study.
#4
Question
There are a number of spelling / syntax errors. The level of English is acceptable but
could be improved.
Answer
This manuscript had been edited by native English-speaking experts of UBM
Medica Asia Pte Ltd at first, and the revised version of this manuscript has been
edited and approved by professional editors of American Journal Experts.
These changes having been made, we hope that BMC ID will accept and publish
our manuscript.
Thank you for your consideration.
Sincerely yours,
Chang-Hua Chen.
On behalf of Chieh-Chen Huang