Prophylactic antibiotics to reduce morbidity and mortality in newborn infants with intercostal catheters
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objective of this review is to determine the effect of prophylactic antibiotics compared to selective use of antibiotics on mortality and morbidity (especially septicaemia) in neonates undergoing placement of an intercostal catheter.
Data permitting, subgroup analysis will be done to determine whether results differ by:
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term (> 37 weeks gestation) versus preterm (< 37 weeks gestation);
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type of antibiotic (e.g., penicillins, macrolides, aminoglycosides, cephalosporins, or combinations);
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type of indication for catheter (e.g., pneumothorax, pleural effusion, post‐operative indications);
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type of prophylaxis (e.g., single dose/s with insertion, ongoing prophylaxis for the life of the catheter);
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whether infant was on antibiotics at the time of study entry.
Background
Description of the condition
Intercostal catheters are commonly used for the drainage of intrathoracic collections in newborn infants including pneumothorax and pleural effusions. The Vermont Oxford Network Database reported an incidence of pneumothorax in infants weighing less than 1500 g ranging from 5.1% to 8.6% (1991 to 1996) (Horbar 2002).
As with any procedure involving breach of the cutaneous barrier, intercostal drainage is a potential risk factor for nosocomial infection. Additionally, by virtue of their underlying illness, patients requiring intercostal catheters may have impaired local and systemic defence mechanisms. Premature and low birth weight infants are particularly at risk. Retrospective data from the National Institute of Child Health and Development (NICHD) Neonatal Research Network, USA, demonstrated an incidence of pneumothorax from 1990 to 2002 of 13% in infants weighing 501 to 750 g and 6% in infants weighing 751 to 1000 g (Fanaroff 2007). In this same population, the incidence of late‐onset septicaemia was 44% and 30% respectively in each of the above weight groups. Hence, the group of premature neonates most likely to require an intercostal catheter are also those most at risk of morbidity and mortality as a result of nosocomial infection.
Infection secondary to the use of intercostal catheters may cause significant morbidity and mortality. Morbidity may include prolonged duration and increased severity of respiratory illness (including chronic lung disease and need for respiratory support) (Greenough 2005), increased length of hospital stay (Mireya 2007) and impaired neurodevelopmental outcome (Stoll 2004).
Documented complications of intercostal catheters in both paediatric and adult populations include localised cellulitis (Margau 2006) and empyema (Bailey 2000). The incidence of empyema following intercostal drainage has been reported at about 2% (Millikan 1980; Chan 1997; Bailey 2000). Potential factors implicated in infection of the drain site and pleural space include failure of aseptic technique, advancement of a pre‐existing drain into the pleural space and duration of intercostal drainage (Tang 2002). Factors that might affect the risk of infection include geographic location of insertion (operating theatre, intensive care unit, retrieval site), patient acuity at the time of catheter placement, and the skill level of the operator have been incompletely studied (Baumann 2003).
There are currently no published recommendations on the use of prophylactic antibiotics for intercostal catheters for non‐traumatic indications. In adult chest trauma patients requiring intercostal drainage, several studies have found evidence of benefit from single‐dose antimicrobial prophylaxis (Grover 1977; LeBlanc 1985; Demetriades 1991) and published evidence based guidelines for chest trauma make a level III recommendation (based on class I and II data) for up to 24 hours cover with a first generation cephalosporin (Luchette 2000). However, for non‐traumatic indications across all age groups there remains variability in practice including timing, target population and choice of antibiotics.
Description of the intervention
Antibiotic prophylaxis is the prescription of antibiotics with the goal of reducing the risk of bacterial infection (Antibiotic Expert Group 2006). In practice, antibiotic prophylaxis is used where there is an increased risk of infection or where the consequence of infection would be significant. The specific choice of antibiotic is determined by the known or likely target organisms.
How the intervention might work
There is a risk of introduction of colonising bacteria into the systemic circulation with any invasive procedure (Dear 2005) including insertion of an intercostal catheter. The use of antibiotic prophylaxis against known or likely target organisms would potentially reduce pathogen load and, therefore, minimise local and systemic infection related to intercostal catheter use.
Why it is important to do this review
There are significant public health implications for failure of judicious antibiotic use (CDC 2004). Antimicrobial prophylaxis, while potentially preventing intercostal catheter‐related soft tissue and bloodstream infection, may have the undesirable effect of promoting the emergence of resistant strains of micro‐organisms (Freij 1999) or of altering the pattern of isolates causing infection (Viudes 2002). At the individual level, there is a risk of adverse effects associated with antibiotic use including ototoxicity and nephrotoxicity (Fanos 1999; Contopoulos‐Ioannidis 2004). Any policy of antimicrobial prophylaxis must take these potential risks into account.
Recent Cochrane systematic reviews on the use of prophylactic antibiotics for neonates with umbilical artery catheters (Inglis 2007), umbilical venous catheters (Inglis 2005) and central venous catheters (Jardine 2008) demonstrated that there was no evidence to either support or refute the use of antimicrobial prophylaxis during the use of such catheters in newborn infants. The following systematic review evaluates the use of prophylactic antibiotics for neonates with intercostal catheters.
Objectives
The objective of this review is to determine the effect of prophylactic antibiotics compared to selective use of antibiotics on mortality and morbidity (especially septicaemia) in neonates undergoing placement of an intercostal catheter.
Data permitting, subgroup analysis will be done to determine whether results differ by:
-
term (> 37 weeks gestation) versus preterm (< 37 weeks gestation);
-
type of antibiotic (e.g., penicillins, macrolides, aminoglycosides, cephalosporins, or combinations);
-
type of indication for catheter (e.g., pneumothorax, pleural effusion, post‐operative indications);
-
type of prophylaxis (e.g., single dose/s with insertion, ongoing prophylaxis for the life of the catheter);
-
whether infant was on antibiotics at the time of study entry.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials or some types of non‐randomised (i.e., quasi‐randomised) controlled trials of adequate quality in which either individual newborn infants or clusters of infants (such as separate neonatal units) were randomised to receive prophylactic antibiotics versus placebo or no treatment.
Types of participants
Neonates with intercostal catheters: full term infants less than 28 days old; preterm infants up to 44 weeks postmenstrual age.
Types of interventions
Any systemic antibiotic (not including antifungals) or combination of antibiotics (either as a single dose or ongoing prophylaxis) versus placebo or no treatment given at the time of catheter insertion. We will not specifically exclude any study that enrolls babies who are or are not receiving a treatment course (or dose or doses) of antibacterial antibiotics.
Types of outcome measures
Primary outcomes
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Mortality (neonatal mortality, mortality prior to discharge or however defined in individual studies)
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Proven bacterial septicaemia (blood culture positive), suspected septicaemia or clinical septicaemia
Secondary outcomes
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Incidence of local soft tissue infection (cellulitis)
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Incidence of empyema
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Chronic lung disease (oxygen requirement at 36 weeks postmenstrual age)
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Duration of ventilation (hours or days)
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Duration of respiratory support (hours or days)
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Duration of oxygen therapy (hours or days)
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Duration of hospital stays (days)
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Number of resistant organisms (i.e., species) causing infection, identified per time period per infant or per cluster unit
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Number of resistant organisms (i.e., species) colonising infants in the study, identified per time period per infant
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Number of resistant organisms (i.e., species) colonising all infants identified per time period per cluster unit
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Neurodevelopmental outcome (cerebral palsy, sensorineural hearing loss, visual impairment and/or developmental delay at one year, 18 months, two years, or five years)
Search methods for identification of studies
The standard methods of the Cochrane Neonatal Review Group Guidelines will be employed.
Electronic searches
See: Cochrane Neonatal Group methods used in reviews.
Searches will be done of MEDLINE (1966 to the latest), CINAHL (1982 to the latest), and the Cochrane Central Register of Controlled Trials (CENTRAL, latest issue of The Cochrane Library) using the following strategy:
MeSH search terms “Thoracostomy” OR "Chest Tubes" OR the textwords ((“intercostal” OR “inter‐costal”) AND “cathet$”) OR “ICC” OR “ICTD” OR “chest drain” OR “chest tube” OR “tube thoracostomy”
AND
MeSH search term “Infant, newborn” OR the textwords “neonat$” OR “infant”
AND
MeSH search term “Antibacterial Agents” OR the textword “antibiotic”
AND
MeSH search terms “Chemoprevention” OR “Antibiotic Prophylaxis” OR the textword “prophyl$”.
Searching other resources
Previous reviews (including cross references) will also be searched. Searches will not be restricted to publications in the English language or published data. Authors will be contacted for additional/missing information.
Data collection and analysis
The the review authors will separately extract, assess and code all data for each study using a form that will be designed specifically for this review. Any standard error of the mean will replaced by the corresponding standard deviation. Any disagreement will be resolved by discussion. For each study, final data will be entered into RevMan by one review author and then checked by a second review author. Any disagreements will be addressed by the third reviewer.
Selection of studies
All randomized, quasi‐randomized controlled trials or cluster trials fulfilling the selection criteria described in the previous section will be included. Two of the review authors will independently search for and assess trials for inclusion and methodological quality. The review authors will resolve any disagreement by discussion.
Data extraction and management
The standard method of the Cochrane Neonatal Review Group will be employed.
Assessment of risk of bias in included studies
Two of the review authors will independently assess risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008). Any disagreement will be resolved by discussion with or by involving a third review author.
The methodological quality of the studies will be assessed using the following criteria:
1) Sequence generation (evaluating possible selection bias): For each included study, we will describe the method used to generate the allocation sequence as: adequate (any truly random process e.g. random number table; computer random number generator); inadequate (any non random process e.g. odd or even date of birth; hospital or clinic record number); or unclear.
2) Allocation concealment (evaluating possible selection bias): For each included study, we will describe the method used to conceal the allocation sequence as: adequate (e.g. telephone or central randomization; consecutively numbered sealed opaque envelopes); inadequate (open random allocation; unsealed or non‐opaque envelopes, alternation; date of birth); or unclear.
3) Blinding (evaluating possible performance bias): For each included study, we will describe the methods used to blind study participants and personnel from knowledge of which intervention a participant received. Blinding will be assessed separately for different outcomes or classes of outcomes. We will assess the methods as: adequate, inadequate or unclear for participants; adequate, inadequate or unclear for personnel; and adequate, inadequate or unclear for outcome assessors.
4) Incomplete outcome data (evaluating possible attrition bias through withdrawals, dropouts, protocol deviations): For each included study and for each outcome, we will describe the completeness of data including attrition and exclusions from the analysis. We will state whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total randomized participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufficient information is reported or can be supplied by the trial authors, we will re‐include missing data in the analyses that we undertake. We will assess methods as: adequate (< 20% missing data); inadequate (≥ 20% missing data) or unclear.
5) Selective reporting bias: For each included study, we will describe how we investigated the possibility of selective outcome reporting bias and what we found. We will assess the methods as: adequate (where it is clear that all of the study's pre‐specified outcomes and all expected outcomes of interest to the review have been reported); inadequate (where not all the study's pre‐specified outcomes have been reported; one or more reported primary outcomes were not pre‐specified; outcomes of interest are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported); or unclear.
6) Other sources of bias: For each included study, we will describe any important concerns we have about other possible sources of bias (for example, whether there was a potential source of bias related to the specific study design or whether the trial was stopped early due to some data‐dependent process). We will assess whether each study was free of other problems that could put it at risk of bias as: yes; no; or unclear.
Measures of treatment effect
For individual study results: for continuous variables, mean differences (MD) and 95% confidence intervals will be reported. For categorical outcomes, the relative risks (RR) and 95% confidence intervals will be reported. For pooled results: for continuous variables, weighted mean differences (WMD) and 95% confidence intervals will be reported. For categorical outcomes, the relative risks (RR) and 95% confidence intervals will be reported. For significant findings, the risk difference (RD) and number needed to treat (NNT) will be calculated. For measures of counts and rates, we will calculate rate ratios.
Assessment of heterogeneity
Where sufficient included studies are available, heterogeneity will be assessed using the I2 test of heterogeneity.
Data synthesis
If meta‐analysis is judged to be appropriate, the analysis will be done using Review Manager software (RevMan 5) supplied by the Cochrane Collaboration. For estimates of typical relative risk and risk difference, we plan to use the Mantel‐Haenszel method. For measured quantities, we plan to use the inverse variance method. All meta‐analyses will be done using the fixed effect model.
Subgroup analysis and investigation of heterogeneity
Data permitting, subgroup analysis will be done to determine whether results differ by:
-
term (> 37 weeks gestation) versus preterm (< 37 weeks gestation);
-
type of antibiotic (e.g., penicillins, macrolides, aminoglycosides, cephalosporins, or combinations);
-
type of indication for catheter (e.g., pneumothorax, pleural effusion, post‐operative indications);
-
type of prophylaxis (e.g., single dose/s with insertion, ongoing prophylaxis for the life of the catheter);
-
whether infant was on antibiotics at the time of study entry.
Sensitivity analysis
Given availability of sufficient data, a sensitivity analysis is planned to see if results differ by quality of included studies (e.g., adequacy of randomisation, quasi‐randomised versus randomised).
