Criteria abstracted from The Users' Guide to Medical Literature, from the Health Information Research Unit and Clinical Epidemiology and Biostatistics, McMaster University

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Article Reviewed:

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Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections.

Raad D, Darouiche ER, Dupuis J.

Ann Intern Med 1997;127:267-274. [abstract]

Reviewed by Stephen Schexnayder, University of Arkansas for Medical Sciences/Arkansas Children's Hospital

Review posted January 29, 1998

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I. What is being studied?:

The study objective:

To determine whether the use of a central venous catheter (CVL) treated with a surfactant (tridodecylmethyl-ammonium chloride) followed by rifampin and minocycline (RF/MN) will reduce CVL infection and bloodstream infections from CVL's.

The study design:

Multicenter, randomized controlled trial.

The patients included:

All adult patients in five Texas Medical Center university-affiliated hospitals who needed central venous catheters. 281 hospitalized patients received a total 298 central venous catheters (CVLs). Approximately two-thirds (65% control, 62% coated with RF/MN) were in the intensive care unit. Patients in both groups were nearly divided among patients with cancer, cardiopulmonary disease, head trauma or neurosurgical procedures, and abdominal surgical procedures.

The patients excluded:

Patients known to be allergic to rifampin and minocycline, who had dermatitis or burn over the insertion site, or who catheters were expected to be in place less than three days. No catheters were changed over guidewires.

The interventions compared:

Plain polyurethane CVL triple lumen catheter vs. CVL triple lumen catheter coated with RF/MN. All catheters were 20 cm long.

The outcomes evaluated:

Catheter colonization (CC) and catheter-related bloodstream infection (CRBSI). Catheter related bloodstream infection was confirmed by pulse-gel electrophoresis.

CC was defined as a positive semi-quantitative culture of an intravascular catheter segment of >15 colony forming units or isolation of more than 1000 CFU by sonification technique. CRBSI was defined as a peripheral blood culture positive with signs of sepsis and no other obvious infection. Data were analyzed with and without the confirmation of molecular typing, as infection can be polyclonal within a species.

II. Are the results of the study valid?

Primary questions:

1. Was the assignment of patients to treatments randomized?

Yes. The catheters were boxed with three coated and three uncoated per case at the manufacturer, and were visibly indistinguishable. Each catheter had a unique identification number.

2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?

Was followup complete?

Yes. 298 catheters were originally inserted; 32 (15 control, 17 RF/MN) were not analyzed because they were not cultured upon removal. 30 were in place for less than three days (not anticipated at enrollment), but were included in the study.

Were patients analyzed in the groups to which they were randomized?

Yes, though patients may have crossed over between groups, as the patient was randomized each time they needed a CVL, and a small number of patients received more than one CVL.

Secondary questions:

3. Were patients, health workers, and study personnel "blind" to treatment?

Yes. The catheters were put into box with three of each catheter type by the manufacturer, with each catheter identified solely by a number. The patient and clinician who inserted the catheter were blinded to the group assignment. There is no mention of the investigators being blinded to the type of catheter.

4. Were the groups similar at the start of the trial?

Yes. Multiple demographic and host risk factors were the same between groups including age, sex, neutropenia, and diagnostic category (cancer, cardiopulmonary disease, head trauma, abdominal surgery) were similar between groups.

The majority of the catheters were placed in the subclavian vein (58% control vs. 61% coated) while most of the remainder were placed in the internal jugular vein. Femoral vein catheters accounted for a very small portion (12% control vs. 8% coated).

5. Aside from the experimental intervention, were the groups treated equally?

All catheters were placed using sterile gowns, gloves,cap, and masks. Skin prep was with either povidone-iodine or chlorhexidine (used at one institution), although one cannot determine the number of catheters placed at that institution from the paper. Therapeutic interventions (antibiotics, blood products, and immunosuppressive drugs) were not statistically different between groups. There were more catheters in the control group inserted into patients for total parenteral nutrition (29 vs. 19) but this difference was not statistically significant.

III. What were the results?

1. How large was the treatment effect?

NOTE: The paper used "risk reduction" rather than relative risk. In order to facilitate comparison between papers, the editors have recalculated the treatment effects into relative risk of treatment vs. control groups. See here for review of RRR, RR, and ARR.

The relative risk of catheter colonization was 0.32 (95% confidence interval 0.17 - 0.60) in the RF/MN group compared to the control group. CRBSI occurred in 7 controls and no RF/MN patients (relative risk 0.07, 95% confidence interval 0.0 -1.21). When analyzed for the 5 of 7 infections confirmed by molecular typing, the relative risk was 0.14% (95% confidence interval 0.02 -0.80).

When measured in infections per 1000 catheter days, there were 0 in the RF/MN group vs. 7.34 in the control group. When analyzed for the 5 of 7 infections confirmed by molecular typing, the rates were 0 vs. 5.16 for the controls.

Multivariate analysis found five factors to be protective:

Factor	Odds ratio	Confidence Interval
RF/MN catheter	0.25	0.12 - 0.53
Female	0.36	0.16 - 0.80
Systemic antibiotics	0.29	0.12 - 0.70
Subclavian vs. internal jugular	0.39	0.18 - 0.84
Subclavian vs. femoral	0.28	0.10 - 0.82
Insertion outside the ICU	0.41	0.18 - 0.96

2. How precise was the estimate of the treatment effect?

The confidence intervals reported show that we can be 95% confident that the risk of catheter colonization is 40% to 83% lower with the use of the RF/MN catheters. RF/MN catheters could reduce the risk of CRBSI by 100% or increase it by 21%.

IV. Will the results help me in caring for my patients?

1. Can the results be applied to my patient care?

This is not clear. Since the organisms isolated in this study are the most frequent cause of CC in children, the results may be valid. However, if the major source of catheter infections is from the skin and many infections were in adult males with beards, we may not see such a great benefit. The catheters may cause more local reaction in children than adults, especially in neonates.

2. Were all clinically important outcomes considered?

Yes. Length of stay (LOS) is an important outcome measure that was not assessed. However, CRBSI is usually strongly correlated with increased LOS.

3. Are the likely treatment benefits worth the potential harms and costs?

This depends on the local CRBSI rate.In one study, CRBSI prolonged the ICU stay by an average of eight days (1). Based on that study and a unit cost of $14 more per RF/MN catheter, if the hospital places 250 catheters per year, the projected cost savings would be approximately $180,000 per year. Whether this cost assumption is applicable to pediatric patients is unknown, but there is little doubt CRBSI increases morbidity and health care costs.

References:

1. Pittet D, Tarara D, Wenzel RP. Nosocomial bloodstream infection in critically ill patients. JAMA 1994; 271:1598-1601.

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Related Reviews:

Maki DG, Stolz SM, Wheeler S, et al. Prevention of Central Venous Catheter-Related Bloodstream Infection by Use of an Antiseptic-Impregnated Catheter. Ann Intern Med 1997; 127:257-266.

• Review, by S. Schexnayder

Darouiche RO, Raad II, Heard SO, et al. A Comparison of Two Antimicrobial-Impregnated Central Venous Catheters. N Engl J Med 1999;340:1-8.

• Review by S. Schexnayder

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