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Cochrane Database of Systematic Reviews

Antibiotics for hospital-acquired pneumonia in children


(Protocol)

Jiang L, Mu D, Zhang L, Gui G, Duan Y, Wan C

Jiang L, Mu D, Zhang L, Gui G, Duan Y, Wan C.


Antibiotics for hospital-acquired pneumonia in children.
Cochrane Database of Systematic Reviews 2016, Issue 6. Art. No.: CD012239.
DOI: 10.1002/14651858.CD012239.

www.cochranelibrary.com

Antibiotics for hospital-acquired pneumonia in children (Protocol)


Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Antibiotics for hospital-acquired pneumonia in children (Protocol) i


Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Protocol]

Antibiotics for hospital-acquired pneumonia in children

Lucan Jiang1 ,2,3,4 , Dezhi Mu5 , Lingli Zhang1,2,3 , Ge Gui1,2,3,4 , Yanjun Duan6 , Chaomin Wan5

1 Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, China. 2 Key Laboratory of Birth
Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, China. 3 Evidence-Based
Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China. 4 West China School of Pharmacy,
Sichuan University, Chengdu, China. 5 Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu,
China. 6 Department of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA

Contact address: Lingli Zhang, Department of Pharmacy, West China Second University Hospital, Sichuan University, No. 17, Section
Three, Ren Min Nan Lu AvenueRoad, Chengdu, Sichuan, 610041, China. zhlingli@sina.com.

Editorial group: Cochrane Acute Respiratory Infections Group.


Publication status and date: New, published in Issue 6, 2016.

Citation: Jiang L, Mu D, Zhang L, Gui G, Duan Y, Wan C. Antibiotics for hospital-acquired pneumonia in children. Cochrane
Database of Systematic Reviews 2016, Issue 6. Art. No.: CD012239. DOI: 10.1002/14651858.CD012239.

Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT

This is the protocol for a review and there is no abstract. The objectives are as follows:

To compare different antibiotics in order to identify effective and safe antibiotic drug therapies for children with hospital-acquired
pneumonia (HAP) (including ventilator-associated pneumonia (VAP) and HAP without mechanical ventilation).

BACKGROUND of hospital-acquired infection in ICUs (Richards 2000; Vincent


2009). Although nearly 90% of episodes of HAP occur during me-
chanical ventilation in ICU patients, it is often difficult to identify
Description of the condition the exact incidence of VAP because of possible overlap with other
lower respiratory tract infections, such as infectious tracheobron-
Hospital-acquired pneumonia (HAP) or nosocomial pneumonia
chitis in mechanically ventilated patients (ATS 2005). Depending
is a type of pneumonia that develops at least 48 hours after being
on the case definition of pneumonia and the population under
admitted to hospital and that was not present at the time of hos-
evaluation, the exact incidence varies widely (Eggimann 2003).
pital admission (NICE 2014). Ventilator-associated pneumonia
Data published by the National Nosocomial Infection Surveillance
(VAP) is a subtype of HAP. VAP is a lung infection diagnosed in
program indicates that in paediatric ICUs, VAP is the second most
patients undergoing mechanical ventilation for at least 48 hours
frequent cause of nosocomial infection (Cernada 2013; Richards
(ATS 2005). HAP and VAP are serious diseases that are often dif-
1999). As such, VAP constitutes 20% of nosocomial infection in
ficult to treat in clinical practice and remain an important cause
paediatric ICUs, with rates of six episodes per 1000 ventilator days
of morbidity and mortality (Song 2008).
(Cernada 2013).
It is estimated that HAP has a rate of 5 to 10 per 1000 hospital
admissions (ATS 2005). For patients in the intensive care unit
(ICU), the incidence of HAP increases significantly; in both Eu-
rope and the United States, pneumonia is the most frequent cause
Antibiotics for hospital-acquired pneumonia in children (Protocol) 1
Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Description of the intervention pathogen, or pathogen resistance to the antimicrobial drug. The
most important independent factor that affects mortality in HAP
Compared with community-acquired pneumonia (CAP), HAP
is inappropriate initial empiric therapy and the delayed application
and VAP are more likely to be infections caused by colonised bac-
of antibiotics (Masterton 2008; Torres 2009). Therefore, once the
teria and multi-drug resistant (MDR) pathogens (ATS 2005). The
diagnosis of bacterial HAP/VAP is established, even when bacteria
pathogens commonly associated with HAP/VAP are aerobic gram-
are not found in respiratory secretions, there is a need for imme-
negative bacilli, such as Pseudomonas aeruginosa (P. aeruginosa), Es-
diate broad-spectrum antimicrobial drugs (Torres 2009). The ini-
cherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and
tial empirical antibiotic selection should cover possible common
Acinetobacter species. For patients with HAP and VAP, the time
bacteria, the patient should be treated and observed for the first
of onset of pneumonia is important for specific pathogens and
three days, and then a decision should be made on whether to
outcomes as an epidemiologic variable and risk factor. Early-onset
continue or change to other options according to the therapeutic
HAP and VAP, occurring within the first four days of hospitalisa-
response. Once pathogens are specific, treatment should immedi-
tion, generally have a better prognosis, and the pathogens are more
ately be changed to sensitive, targeted narrow-spectrum antimicro-
likely to be antibiotic-sensitive bacteria, such as Streptococcus pneu-
bial drugs (Torres 2009). In addition, all antibiotics for HAP/VAP
moniae (S. pneumoniae), Haemophilus influenzae (H. influenzae),
should be selected according to the local epidemiological data.
Staphylococcus aureus (S. aureus), E. coli and K. pneumoniae; while
late-onset HAP and VAP (five days or more of hospitalisation) are
more likely to be caused by MDR pathogens (including S. aureus,
P. aeruginosa, K. pneumoniae and Enterobacter spp et al), and results
How the intervention might work
in increased patient mortality and morbidity. The number of pa-
tients with HAP caused by MDR pathogens such as methicillin- Pneumonia is the leading cause of mortality in children below the
resistantS. aureus (MRSA), P. aeruginosa and Acinetobacter spp et age of five (WHO 2015). Identifying pathogens in children with
al shows an increasing trend. However, colonisation and infection pneumonia is not easy, and to meet public health goals of reducing
with MDR pathogens is more likely to happen in patients with childhood mortality caused by pneumonia, appropriate antibiotic
early-onset HAP who have received prior antibiotics or who have administration is employed in most instances (Lodha 2013). As
had prior hospitalisation within the previous 90 days; these pa- appropriate antimicrobial treatment for patients with HAP will
tients, they should be treated similar to patients with late-onset significantly improve prognosis, more rapid identification of in-
HAP or VAP. According to the ATS guideline (ATS 2005), the fection and accurate selection of antimicrobial agents for patients
key decision in initial empiric therapy is whether the patient has are vital clinical goals we should focus on (Chastre 2002; Kollef
risk factors for MDR organisms rather than the time of onset of 2003).
HAP/VAP (Selim 2010). Other risk factors for MDR pathogens
include (ATS 2005):
1. antimicrobial therapy in the preceding 90 days;
2. current hospitalisation of five days or more; Why it is important to do this review
3. high frequency of antibiotic resistance in the community or A guideline published in 2005 by the American Thoracic Soci-
in the specific hospital unit; ety and Infectious Diseases Society of America recommended an-
4. immunosuppressive disease and/or therapy; tibiotics specifically for adults with HAP (ATS 2005). The latest
5. presence of risk factors for healthcare-associated pneumonia edition of Therapeutic Guidelines does not address children with
(HCAP). HAP (only listing paediatric doses in an adult framework) (NICE
Empiric therapy is defined as the use of antibiotics before the 2014). Also, antibiotic administration is at the core of treatment
confirmation of a definitive diagnosis of infection, and where the of HAP in children, and its optimal management remains contro-
patient would face greater risk by observation than by treatment versial. Therefore, it is important to know what the best manage-
(Kim 1989). In contrast, the primary objective of directed ther- ment is for HAP in children.
apy is to help confirm a suspected diagnosis, involving a specific
treatment of pre-determined duration (Kim 1989). The follow-
ing statement explains the principles determining antimicrobial
use for HAP: “Choose empiric antimicrobial wisely (broad-spec-
trum), start early, hit hard with an appropriate dosing schedule,
OBJECTIVES
de-escalate rapidly (narrow spectrum) and stop abruptly (post ad-
equate duration)” (Morrow 2009). The ATS guideline indicates To compare different antibiotics in order to identify effective and
that individual empirical antibiotic selection should be based on safe antibiotic drug therapies for children with hospital-acquired
the risk for MDR pathogens (Selim 2010). Inappropriate initial pneumonia (HAP) (including ventilator-associated pneumonia
antimicrobial therapy refers to drugs not covered by the target (VAP) and HAP without mechanical ventilation).

Antibiotics for hospital-acquired pneumonia in children (Protocol) 2


Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
METHODS completion of treatment, or oxygen saturation of less than 90%
(measured by pulse oximetry) after completion of the treatment.
Loss to follow-up or withdrawal from the study at any time after
Criteria for considering studies for this review recruitment will indicate failure in the analysis.
3. Mortality rate.

Types of studies
We will include all randomised controlled trials (RCTs) comparing Secondary outcomes
antibiotic treatment regimens for children with HAP (including The clinically relevant outcome measures will be as follows.
VAP and HAP without mechanical ventilation). 1. Relapse rate: defined as children declared ’cured’, but
developing recurrence of disease at follow-up in a defined period.
2. Length of hospital stay: duration of total hospital stay (from
Types of participants
day of admission to discharge) in days.
We will include children up to (not including) 18 years of age with 3. Need for change in antibiotics: children requiring change in
HAP (including VAP and HAP without mechanical ventilation) antibiotics from the primary regimen.
diagnosed by clinical and/or radiological features and/or quantita- 4. Attributable adverse events and/or any events requiring
tive culture of respiratory specimens. We will also include studies discontinuation of the trial antibiotic.
of children with suspected HAP/VAP. The participants must have
signs and symptoms of a pneumonia infection, including: fever;
leukocytosis (increased numbers of white blood cells); and/or pu-
rulent tracheal secretions. We will exclude data from children with
Search methods for identification of studies
immune suppression or dysfunction related to primary diagnoses.
We will exclude data from children at-risk due to disorders such as
cystic fibrosis, primary ciliary dyskinesia, congenital heart disease,
etc. We will also exclude data from neonates. Electronic searches
We will identify trials from searches of the following databases:
Types of interventions 1. Cochrane Acute Respiratory Infections Group Trials
We will include studies comparing one antibiotic regimen with Register;
another antibiotic regimen or placebo. We will also include tri- 2. Cochrane Central Register of Controlled Trials
als evaluating monotherapy versus combination therapy. We will (CENTRAL) in the Cochrane Library;
classify antibiotic groups as follows. 3. MEDLINE (Ovid);
1. β-lactams. 4. Embase.com;
2. Lincosamides. 5. LILACS;
3. Glycopeptide antibiotics. 6. Chinese Biomedical Literature Database (CBM).
4. Quinolones. The proposed MEDLINE strategy is shown in Appendix 1. We
5. Aminoglycosides. will combine this with the Cochrane highly sensitive search strat-
6. Macrolides. egy for identifying randomised trials sensitivity- and precision-
7. Antibacerial oxazolidinone agents. maximising version (2008 revision) and adapt this for use in the
8. Anti anaerobic antibiotics fungi: e.g. Flagyl. other databases. We will also conduct a search of ClinicalTri-
als.gov (http://clinicaltrials.gov) and the World Health Organiza-
tion (WHO) International Clinical Trials Registry Platform (IC-
Types of outcome measures TRP) (www.who.int/ictrp/en/). We will search all databases from
their inception to the present and we will not impose any restric-
tion on the language of publication.
Primary outcomes
1. Clinical cure. The definition of clinical cure is symptomatic
and involves clinical recovery by the end of treatment. Searching other resources
2. Treatment failure rates. The definition of treatment failure
is the presence of any of the following: development of chest We will contact authors/experts in the field for unpublished and
indrawing, convulsions, drowsiness or inability to drink at any ongoing trials. We will also check the reference lists of retrieved
time, respiratory rate above the age-specific cut-off point on studies. We will not apply any language restrictions.

Antibiotics for hospital-acquired pneumonia in children (Protocol) 3


Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Data collection and analysis summarise the risk of bias judgements across different studies for
each of the domains listed. We will consider blinding separately
for different key outcomes, where necessary. Where information
Selection of studies on risk of bias relates to unpublished data or correspondence with
a trialist, we will note this in the ’Risk of bias’ table.
Two review authors (LJ, GG) will independently screen titles and
When considering treatment effects, we will take into account the
abstracts for inclusion of all the potential studies we identify as a
risk of bias for the studies that contribute to that outcome.
result of the search.
We will retrieve the full-text study reports/publication and two
review authors (LJ, CW) will independently screen the full-text
Assesment of bias in conducting the systematic
and identify studies for inclusion, and identify and record reasons
review
for exclusion of the ineligible studies. We will resolve any disagree-
ment through discussion or, if required, we will consult a third We will conduct the review according to this published protocol
review author (LZ). We will identify and exclude duplicates and and report any deviations from it in the ’Differences between pro-
collate multiple reports of the same study so that each study rather tocol and review’ section of the systematic review.
than each report is the unit of interest in the review. We will record
the selection process in sufficient detail to complete a PRISMA
Measures of treatment effect
flow diagram (BMJ 2009) and ’Characteristics of excluded studies’
table. For dichotomous data, we will present results as summary risk
ratios (RRs) or odds ratio (ORs) with 95% confidence intervals
(CIs); we will also use the RR to measure time-to-event data.
Data extraction and management We will use the mean difference (MD) for measuring continuous
Two review authors (LJ, GG) will independently extract data using data. For trials that measure the same outcome, but use different
pre-designed forms. We will resolve discrepancies through consen- methods, we will use the standardised mean difference (SMD) to
sus or, if required, we will consult a third review author (DM). The combine results.
extracted data will include the following information: details of
source, eligibility, methods, participants, interventions, outcomes
and results. Unit of analysis issues
If any included studies involve both children and adults, we will We will include cluster-randomised trials and cross-over trials
extract data separately for children. If any of the information above along with individually-randomised trials. In this systematic re-
is inadequate, we will contact the authors of the primary study to view, we will treat each group or cluster in cluster-randomised trials
provide further details and clarification. as the unit of analysis; we will use the intracluster correlation coeffi-
If any included studies are not in English or Chinese, we will cient (ICC) to estimate the relative variability within and between
contact translators with relevant language skills to help us extract clusters, according to the relevant section of the Cochrane Hand-
the necessary data. book for Systematic Reviews of Interventions (Higgins 2011). For
cross-over trials with binary outcomes, we will adopt the Becker-
Balagtas approach to combine cross-over trials with parallel trials
Assessment of risk of bias in included studies for meta-analysis (Stedman 2011). For cross-over trials with con-
Two review authors (LJ, YD) will independently assess risk of bias tinuous outcomes, each individual will act as the unit of analysis
according to the following domains using the criteria outlined in and we will conduct approximate paired analyses (Higgins 2011).
the Cochrane Handbook for Systematic Reviews of Interventions (
Higgins 2011). We will resolve disagreements by discussion among
co-authors. Dealing with missing data
1. Random sequence generation. We will conduct intention-to-treat analyses, when data on indi-
2. Allocation concealment. viduals are missing, such as when randomised participants are ex-
3. Blinding of participants and personnel. cluded from the analysis. We will follow recommendations in the
4. Blinding of outcome assessment. Cochrane Handbook for Systematic Reviews of Interventions regard-
5. Incomplete outcome data. ing strategies for dealing with missing data (Higgins 2011). These
6. Selective outcome reporting. are:
7. Other bias. 1. whenever possible, we will contact the original investigators
We will grade each potential source of bias as high, low or unclear to request missing data;
and provide a quote from the study report, together with a jus- 2. we will make explicit the assumptions of any methods used
tification for our judgement in the ’Risk of bias’ tables. We will to cope with missing data: for example, that the data are assumed

Antibiotics for hospital-acquired pneumonia in children (Protocol) 4


Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
missing at random, or that missing values were assumed to have we use random-effects analyses, the results will be presented as the
a particular value such as a poor outcome; average treatment effect with 95% confidence intervals, and the
3. we will perform sensitivity analyses to assess how sensitive estimates of I2 statistic. If appropriate, a Network meta-analyses
results are to reasonable changes in the assumptions that are would be considered.
made; and
4. we will address the potential impact of missing data on the
findings of the review in the discussion section. GRADE and ’Summary of findings’ table
The minimum number of contact attempts we will try will be We will create a ’Summary of findings’ table using the following
three. outcomes: clinical cure, treatment failure rates, relapse rate, need
for change in antibiotics, mortality rate, length of hospital stay
and adverse events reported. We will use the five GRADE con-
Assessment of heterogeneity siderations (study limitations, consistency of effect, imprecision,
We will assess heterogeneity among studies in two ways. Firstly, we indirectness and publication bias) to assess the quality of a body
will assess heterogeneity at face value: heterogeneity in population, of evidence as it relates to the studies which contribute data to the
interventions, or outcomes. Secondly, we will use a Chi2 test (P ≤ meta-analyses for the prespecified outcomes (GRADE 2004). We
0.10 is considered to be consistent with statistical heterogeneity) will use methods and recommendations described in Section 8.5
and the I2 statistic to assess presence of statistical heterogeneity (> and Chapter 12 of the Cochrane Handbook for Systematic Reviews
50% is substantial heterogeneity, > 75% is considerable hetero- of Interventions (Higgins 2011) using GRADEproGDT software
geneity; Higgins 2011). (GRADEproGDT 2015). We will justify all decisions to down- or
up-grade the quality of studies using footnotes and we will make
comments to aid the reader’s understanding of the review where
Assessment of reporting biases necessary.
We will use funnel plots to detect small-study effects including
publication bias, if we find a sufficient number of studies. We will Subgroup analysis and investigation of heterogeneity
assess funnel plot asymmetry visually. If asymmetry is suggested
We will perform a subgroup analysis of:
by a visual assessment, we will perform exploratory analyses to
1. early-onset HAP versus late-onset HAP (HAP without
investigate it.
mechanical ventilation);
2. early-onset VAP versus late-onset VAP.
Data synthesis
We will carry out statistical analysis using the Review Manager Sensitivity analysis
software (RevMan 2014). We will use fixed-effect meta-analysis We will perform a sensitivity analysis of the impact of high risk of
for combining data where it is reasonable to assume that studies bias on the outcome of the meta-analysis.
are estimating the same underlying treatment effect: i.e. where tri-
als are examining the same intervention, and the trials’ popula-
tions and methods are judged sufficiently similar. If there is clin-
ical heterogeneity sufficient to expect that the underlying treat-
ACKNOWLEDGEMENTS
ment effects differ between trials, or if statistical heterogeneity is
detected (I2 statistic > 0%), we will use random-effects meta-anal- The methods section of this protocol is based on a standard tem-
ysis to produce an overall summary, if an average treatment effect plate developed by the Cochrane Airways Group and adapted by
across trials is considered clinically meaningful. The random-ef- the Cochrane Acute Respiratory Infections Group. Many thanks
fects summary will be treated as the average of the range of possible to all authors’ affiliated Institutions and organisations, and thanks
treatment effects and we will discuss the clinical implications of to the Co-ordinating Editors, Referees and Editors of the Cochrane
treatment effects differing between trials. If the average treatment Acute Respiratory Infections Group for their comments and en-
effect is not clinically meaningful, we will not combine trials. If couragement.

Antibiotics for hospital-acquired pneumonia in children (Protocol) 5


Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
REFERENCES

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Indicates the major publication for the study

APPENDICES

Appendix 1. Detailed search strategies


exp Pneumonia/ OR (pneumon* or bronchopneumon* or pleuropneumon* or tracheobronchit* or tracheo bronchit*).tw. OR (vap or
hap or hcap).tw. OR Respiratory Tract Infections/ OR (respiratory infection* or respiratory tract infection*).tw. OR exp Ventilators,
Mechanical/ OR ventilat*.tw. OR intubation/ OR intubation, intratracheal/ OR intubat*.tw. OR exp Drug Resistance, Bacterial/ OR
drug resistance, multiple/ OR drug resistance, multiple, bacterial/ OR (bacteria* adj2 ((multidrug or multi-drug or multiple drug or
antibiotic) adj2 resistan*)).tw. OR (mdr or mdro).tw.
AND
exp Anti-Bacterial Agents/ OR (antibiotic* or antibacterial* or anti-bacterial* or antimicrobial* or anti-microbial*).tw. OR Amikacin/
OR Colistin/ OR Vancomycin/ OR exp Gentamicins/ OR (amikacin* or colistin* or vancomycin* or gentamicin* or gen-
tamycin*).tw,nm.
AND
exp Infant/ OR exp Child/ OR exp Adolescent/ OR exp Minors/ OR exp Puberty/ OR exp Pediatrics/ OR exp Schools/ OR (Infant* OR
infancy OR Newborn* OR Baby* OR Babies OR Neonat* OR Preterm* OR Prematur* OR Postmatur* OR Child* OR Schoolchild*
OR School age* OR Preschool* OR Kid or kids OR Toddler* OR Adoles* OR Teen* OR Boy* OR Girl* OR Minors* OR Pubert*
OR Pubescen* OR Prepubescen* OR Paediatric* OR Paediatric* OR Peadiatric* OR Nursery school* OR Kindergar* OR Primary
school* OR Secondary school* OR Elementary school* OR High school* OR Highschool*)
AND
((randomized controlled trial or controlled clinical trial).pt. or randomized.ab. or randomised.ab. or placebo.ab. or drug therapy.fs. or
randomly.ab. or trial.ab. or groups.ab.) not (exp animals/ not humans.sh.)

CONTRIBUTIONS OF AUTHORS

Roles and responsibilities

Task Responsible

Protocol stage: draft the protocol Lucan Jiang, Lingli Zhang

Antibiotics for hospital-acquired pneumonia in children (Protocol) 7


Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)

Review stage: select which trials to include (2 + 1 arbiter) Lucan Jiang, Ge Gui, Chaomin Wan

Review stage: extract data from trials (2 + 1 arbiter) Lucan Jiang, Ge Gui, Dezhi Mu

Review stage: enter data into RevMan Lucan Jiang, Ge Gui

Review stage: carry-out the analysis Yanjun Duan, Lingli Zhang

Review stage: interpret the analysis Yanjun Duan, Chaomin Wan

Review stage: draft the final review Lucan Jiang, Dezhi Mu, Lingli Zhang

Update stage: update the review Lucan Jiang, Lingli Zhang

DECLARATIONS OF INTEREST
Lucan Jiang: no known conflicts of interest.
Dezhi Mu: no known conflicts of interest.
Lingli Zhang: National Natural Science Foundation of China(No. 81373381&#65289. The grant of National Natural Science
Foundation of China has no role in study design, data collection and analysis or preparation of this review.
Ge Gui: no known conflicts of interest.
Yanjun Duan: no known conflicts of interest.
Chaomin Wan: no known conflicts of interest.

SOURCES OF SUPPORT

Internal sources
• Sichuan University, China.

External sources
• Natural Science Foundation of China, China.
Evidence based establishment of evaluation index system for paediatric rational drug use in China (No. 81373381)

Antibiotics for hospital-acquired pneumonia in children (Protocol) 8


Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.