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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Single-drug therapy or selective decontamination of the digestive tract as antifungal prophylaxis in critically ill patients: a systematic review

JW van Till, O van Ruler, B Lamme, RJ Weber, JB Reitsma, and MA Boermeester.

Review published: 2007.

CRD summary

The authors concluded that single-drug antifungal prophylaxis and selective decontamination of the digestive tract (SDD) reduced yeast colonisation and infections in critically ill patients; most yeast-related outcomes appeared to be more effectively reduced by SDD. The evidence appears to support the authors’ conclusions, but poor reporting of the review methods makes it difficult to comment on the reliability of these conclusions.

Authors' objectives

To evaluate the effects of single-drug antifungal prophylaxis (SAP) and selective decontamination of the digestive tract (SDD) in non-neutropenic critically ill adults, and to compare SAP with SDD.

Searching

MEDLINE (1966 to January 2006), the Cochrane Database of Systematic Reviews, the Cochrane CENTRAL Register, DARE and EMBASE (1950 to January 2006) were searched; the search terms were reported. Studies reported in English, French or German were eligible. In addition, the reference lists of eligible studies were screened. Unpublished data and data from studies reported only as abstracts were excluded.

Study selection

Prospective clinical trials that compared the effects of preventive (either pre-emptive or prophylactic) antifungal therapy with no antifungal agent in non-neutropenic adults who did not have concurrent immune suppression were eligible for inclusion. Studies had to report the incidence of Candida or yeast infection or colonisation. The review assessed yeast colonisation (positive yeast cultures from sputum, stool, urine and /or wound without clinical signs of infection or inflammation), invasive yeast infection (positive yeast cultures from presumed sterile sites with clinical signs of infection or inflammation), candidaemia (positive yeast culture in two or more blood cultures), all-cause in-hospital mortality and mortality directly attributable to yeast infection.

Most of the included studies were randomised controlled trials (RCTs). Most of the SAP studies evaluated fluconazole; other SAP studies evaluated nystatin, clotrimazole and ketoconazole. Most SDD studies evaluated oral amphotericin; other SDD studies evaluated nystatin. The participants included surgical, trauma and medical patients. Median values for patient characteristics were as follows: age 55 years, females 38%, Acute Physiology and Chronic Health Evaluation II (APACHE) score 16 and surgical patients 49%.

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

Validity was assessed using the Jadad scale, which considers randomisation, blinding and withdrawals. The maximum possible score was 5 points. It appears that only RCTs were assessed for validity.

One reviewer assessed validity.

Data extraction

Results data were extracted as odds ratios (ORs) with 95% confidence intervals (CIs), according to review-defined outcomes.

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction.

Methods of synthesis

Pooled ORs with 95% CIs were calculated separately for SAP and SDD using random-effects models. Statistical heterogeneity was assessed using the Q statistic and the I2 statistic. The difference between ORs for SAP and SDD was tested formally, and where there was no significant difference the results from both types of treatment were combined. The number-needed-to-treat (NNT) with antifungal therapy to prevent one adverse outcome was calculated. Publication bias was assessed by calculating the number of studies with null results required to change statistically significant results to non significant results (fail-safe N). The influence of sample size and percentage of surgical patients was examined. For studies of SAP, the effects of systemic drugs were compared with non-absorbable enteral antifungal drugs using logistic regression.

Results of the review

Thirty-three prospective studies (n=5,529) were included. Eleven studies evaluated SAP: 10 RCTs and one prospective intervention study with a historical control group. Twenty-two studies evaluated SDD: 19 RCTs, 2 prospective cohort studies and one non-randomised study with a placebo control group.

The median Jadad quality score for RCTs was 3.5. Twenty-RCTs described the method of randomisation and 15 RCTs were double-blind.

The risk of yeast colonisation was statistically significantly reduced with SAP (OR 0.38, 95% CI: 0.20, 0.70; NNT 5; 5 studies; fail-safe N 25) and SDD (OR 0.12, 95% CI: 0.05, 0.29; NNT 3; 10 studies; fail-safe N 194) compared with controls. Significant heterogeneity was found amongst studies of SDD (p<0.001, I2=73.5%) but not amongst those of SAP (p=0.10). The treatment effect was significantly greater with SDD than with SAP (OR 3.62, 95% CI: 1.12, 11.77). Fail-safe N values were 25 for SAP and 194 for SDD.

The risk of invasive infection was statistically significantly reduced with SAP (OR 0.54, 95% CI: 0.39, 0.75; NNT 20; 10 studies; fail-safe N 26) and SDD (OR 0.29, 95% CI: 0.18, 0.45; NNT 18; 15 studies; fail-safe N 101) compared with controls. No significant heterogeneity was found for either analysis (p=0.40 and p=0.45). The treatment effect was significantly greater with SDD than with SAP (OR 2.0, 95% CI: 1.1, 3.7). Fail-safe N values for yeast infection were 26 for SAP and 101 for SDD.

The risk of candidaemia was statistically significantly reduced with SAP (OR 0.32, 95% CI: 0.12, 0.82; NNT 38; 6 studies), but not with SDD (OR 0.59, 95% CI: 0.25, 1.40; 12 studies), compared with control. No significant heterogeneity was found for either analysis (p=0.25 and p=0.71). There was no significant difference between ORs for SAP and SDD (p=0.34). The fail-safe N was 25 for SAP.

All-cause mortality was reduced with SAP (OR 0.80, 95% CI: 0.64, 1.00; 11 studies) and significantly reduced with SDD (OR 0.73, 95% CI: 0.59, 0.93; NNT 15; 21 studies) compared with controls. No significant heterogeneity was found for either analysis (p=0.61 and p=0.10). There was no significant difference between the ORs for SAP and SDD (p=0.58). The fail-safe N was 41 for SDD.

Mortality directly attributable to yeast infection was significantly reduced with antifungal prophylaxis (OR 0.23, 95% CI: 0.09, 0.60; NNT 41; 6 studies).

Authors' conclusions

Both SAP and SDD reduced yeast colonisation and infections in critically ill patients. Indirect comparisons suggested that yeast-related outcomes (except candidaemia) were more effectively reduced by SDD.

CRD commentary

The review question was stated clearly. Several relevant sources were searched and some attempts were made to limit language bias; although there were no attempts to minimise publication bias, the authors did assess the potential for this. The validity assessment appeared to be limited to RCTs despite the inclusion of studies of other designs. The methods used to select studies and extract the data were not described, so it is not known whether any efforts were made to reduce reviewer error and bias. Only one author assessed validity and this lack of duplication could have led to the introduction of reviewer error and bias. RCTs and non-randomised studies were combined using meta-analyses and heterogeneity was assessed. However, it is questionable whether combining studies with different designs is appropriate. Most of the included studies were RCTs and it was not clear why the authors did not analyse these studies separately. The evidence appears to support the authors’ conclusions, but incomplete reporting of the review methods makes it difficult to comment on the reliability of these conclusions.

Implications of the review for practice and research

Practice: The authors stated that systemic therapy may be recommended for patients at high risk of Candida bloodstream infections and SDD may be used to prevent Candida colonisation and infection in critically ill patients.

Research: The authors did not state any implications for further research.

Funding

Dutch Digestive Diseases Foundation, grant number WS 00-54.

Bibliographic details

van Till J W, van Ruler O, Lamme B, Weber R J, Reitsma J B, Boermeester M A. Single-drug therapy or selective decontamination of the digestive tract as antifungal prophylaxis in critically ill patients: a systematic review. Critical Care 2007; 11(6): R126. [PMC free article: PMC2246222] [PubMed: 18067657]

Indexing Status

Subject indexing assigned by NLM

MeSH

Antifungal Agents /administration & dosage; Candidiasis /drug therapy /microbiology /mortality; Critical Illness /mortality; Decontamination /methods; Gastrointestinal Tract /drug effects /microbiology; Hospital Mortality /trends; Humans

AccessionNumber

12008102730

Database entry date

01/12/2008

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 18067657

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