Antibiotic-impregnated Central Venous Catheters Research Articles

Antibiotic-impregnated central venous catheters in the neonatal intensive care unit—PREVAILing questions

Antibiotic-impregnated central venous catheters in the neonatal intensive care unit—PREVAILing questions

Abstract P-379: EFFECT OF ANTIBIOTIC IMPREGNATED CENTRAL VENOUS CATHETERS ON SERIOUS THROMBOSIS IN THE PEDIATRIC INTENSIVE CARE SETTING

Aims & Objectives: The CATCH clinical trial found antibiotic impregnated central venous catheters (CVCs) reduced bloodstream infections compared to heparin bonded or standard CVCs in paediatric intensive care units (PICUs), but evidence is lacking on the effect of antibiotic impregnation on clinical signs of serious thrombosis, resulting in CVC removal. Methods 1859 children (<16 years) admitted to 14 English PICUs between December 2010 and November 2012 who required a CVC for ≥3 days were randomised to receive, antibiotic impregnated, heparin bonded, or standard CVC. Consent was obtained for analysis of 1485 CVCs. Signs of two episodes of difficulty withdrawing blood or flushing, swollen limb, positive ultrasound and CVC removal due to thrombosis were documented. Observational analysis was used to create a clinically significant thrombosis definition based on what signs were predictive of CVC removal (serious thrombosis). Cox proportional hazard regression was used for three-ways comparisons between CVC types, adjusting for significant risk factors: age, cardiovascular admission, femoral insertion, anticoagulant use and systemic infection. Results Swollen limb was an early sign of thrombosis (median 2.5 days from insertion) and occurred in 40.6% (41/101) of CVC removals. Serious thrombosis was defined by one report of swollen limb or CVC removal. Significant risk factors were femoral insertion and systemic infection. No difference was found between antibiotic impregnated versus standard CVCs (Hazard ratio:1.32:95% confidence interval;0.91,1.93) nor antibiotic impregnated versus heparin bonded CVCs(HR:0.98;0.68,1.40) in time to serious thrombosis. Conclusions Antibiotic impregnated CVCs do not increase risk of serious thrombosis compared to heparin bonded or standard CVCs in children.

Antibiotic-Impregnated Central Venous Catheters Do Not Change Antibiotic Resistance Patterns

Antibiotic-impregnated central venous catheters (CVCs) decrease the incidence of infection in high-risk patients. However, use of these catheters carries the hypothetical risk of inducing antibiotic resistance. We hypothesized that routine use of minocycline and rifampin-impregnated catheters (MR-CVC) in a single intensive care unit (ICU) would change the resistance profile for Staphylococcus aureus. We reviewed antibiotic susceptibilities of S. aureus isolates obtained from blood cultures in a large urban teaching hospital from 2002-2015. Resistance patterns were compared before and after implementation of MR-CVC use in the surgical ICU (SICU) in August 2006. We also compared resistance patterns of S. aureus obtained in other ICUs and in non-ICU patients, in whom MR-CVCs were not used. Data for rifampin, oxacillin, and clindamycin were available for 9,703 cultures; tetracycline resistance data were available for 4,627 cultures. After implementation of MR-CVC use in the SICU, rifampin resistance remained unchanged, with rates the same as in other ICU and non-ICU populations (3%). After six years of use of MR-CVCs in the SICU, the rate of tetracycline resistance was unchanged in all facilities (1%-3%). The use of MR-CVCs was not associated with any change in S. aureus oxacillin-resistance rates in the SICU (66% vs. 60%). However, there was a significant decrease in S. aureus clindamycin resistance (59% vs. 34%; p < 0.05) in SICU patients. Routine use of rifampin-minocycline-impregnated CVCs in the SICU was not associated with increased resistance of S. aureus isolates to rifampin or tetracyclines.

Antibiotic-Impregnated Central Venous Catheters for the Prevention of Catheter-Related Bloodstream Infection in Children: A Meta-Analysis

Antibiotic-Impregnated Central Venous Catheters for the Prevention of Catheter-Related Bloodstream Infection in Children: A Meta-Analysis

Cost-Effectiveness of Pediatric Central Venous Catheters in the UK: A Secondary Publication from the CATCH Clinical Trial.

Background: Antibiotic-impregnated central venous catheters (CVCs) reduce the risk of bloodstream infections (BSIs) in patients treated in pediatric intensive care units (PICUs). However, it is unclear if they are cost-effective from the perspective of the National Health Service (NHS) in the UK.Methods: Economic evaluation alongside the CATCH trial (ISRCTN34884569) to estimate the incremental cost effectiveness ratio (ICER) of antibiotic-impregnated (rifampicin and minocycline), heparin-bonded and standard polyurethane CVCs. The 6-month costs of CVCs and hospital admissions and visits were determined from administrative hospital data and case report forms.Results: BSIs were detected in 3.59% (18/502) of patients randomized to standard, 1.44% (7/486) to antibiotic and 3.42% (17/497) to heparin CVCs. Lengths of hospital stay did not differ between intervention groups. Total mean costs (95% confidence interval) were: £45,663 (£41,647–£50,009) for antibiotic, £42,065 (£38,322–£46,110) for heparin, and £44,503 (£40,619–£48,666) for standard CVCs. As heparin CVCs were not clinically effective at reducing BSI rate compared to standard CVCs, they were considered not to be cost-effective. The ICER for antibiotic vs. standard CVCs, of £54,057 per BSI avoided, was sensitive to the analytical time horizon.Conclusions: Substituting standard CVCs for antibiotic CVCs in PICUs will result in reduced occurrence of BSI but there is uncertainty as to whether this would be a cost-effective strategy for the NHS.

Generalisability and Cost-Impact of Antibiotic-Impregnated Central Venous Catheters for Reducing Risk of Bloodstream Infection in Paediatric Intensive Care Units in England.

BackgroundWe determined the generalisability and cost-impact of adopting antibiotic-impregnated CVCs in all paediatric intensive care units (PICUs) in England, based on results from a large randomised controlled trial (the CATCH trial; ISRCTN34884569).MethodsBSI rates using standard CVCs were estimated through linkage of national PICU audit data (PICANet) with laboratory surveillance data. We estimated the number of BSI averted if PICUs switched from standard to antibiotic-impregnated CVCs by applying the CATCH trial rate-ratio (0.40; 95% CI 0.17,0.97) to the BSI rate using standard CVCs. The value of healthcare resources made available by averting one BSI as estimated from the trial economic analysis was £10,975; 95% CI -£2,801,£24,751.ResultsThe BSI rate using standard CVCs was 4.58 (95% CI 4.42,4.74) per 1000 CVC-days in 2012. Applying the rate-ratio gave 232 BSI averted using antibiotic CVCs. The additional cost of purchasing antibiotic-impregnated compared with standard CVCs was £36 for each child, corresponding to additional costs of £317,916 for an estimated 8831 CVCs required in PICUs in 2012. Based on 2012 BSI rates, management of BSI in PICUs cost £2.5 million annually (95% uncertainty interval: -£160,986, £5,603,005). The additional cost of antibiotic CVCs would be less than the value of resources associated with managing BSI in PICUs with standard BSI rates >1.2 per 1000 CVC-days.ConclusionsThe cost of introducing antibiotic-impregnated CVCs is less than the cost associated with managing BSIs occurring with standard CVCs. The long-term benefits of preventing BSI could mean that antibiotic CVCs are cost-effective even in PICUs with extremely low BSI rates.

Impregnated central venous catheters for prevention of bloodstream infection in children (the CATCH trial): a randomised controlled trial.

Impregnated central venous catheters are recommended for adults to reduce bloodstream infections but not for children because there is not enough evidence to prove they are effective. We aimed to assess the effectiveness of any type of impregnation (antibiotic or heparin) compared with standard central venous catheters to prevent bloodstream infections in children needing intensive care. We did a randomised controlled trial of children admitted to 14 English paediatric intensive care units. Children younger than 16 years were eligible if they were admitted or being prepared for admission to a participating paediatric intensive care unit and were expected to need a central venous catheter for 3 or more days. Children were randomly assigned (1:1:1) to receive a central venous catheter impregnated with antibiotics, a central venous catheter impregnated with heparin, or a standard central venous catheter with computer generated randomisation in blocks of three and six, stratified by method of consent, site, and envelope storage location within the site. The clinician responsible for inserting the central venous catheter was not masked to allocation, but allocation was concealed from patients, their parents, and the paediatric intensive care unit personnel responsible for their care. The primary outcome was time to first bloodstream infection between 48 h after randomisation and 48 h after central venous catheter removal with impregnated (antibiotic or heparin) versus standard central venous catheters, assessed in the intention-to-treat population. Safety analyses compared central venous catheter-related adverse events in the subset of children for whom central venous catheter insertion was attempted (per-protocol population). This trial is registered with ISRCTN number, ISRCTN34884569. Between Nov 25, 2010, and Nov 30, 2012, 1485 children were recruited to this study. We randomly assigned 502 children to receive standard central venous catheters, 486 to receive antibiotic-impregnated catheters, and 497 to receive heparin-impregnated catheters. Bloodstream infection occurred in 18 (4%) of those in the standard catheters group, 7 (1%) in the antibiotic-impregnated group, and 17 (3%) assigned to heparin-impregnated catheters. Primary analyses showed no effect of impregnated (antibiotic or heparin) catheters compared with standard central venous catheters (hazard ratio [HR] for time to first bloodstream infection 0.71, 95% CI 0.37-1.34). Secondary analyses showed that antibiotic central venous catheters were better than standard central venous catheters (HR 0.43, 0.20-0.96) and heparin central venous catheters (HR 0.42, 0.19-0.93), but heparin did not differ from standard central venous catheters (HR 1.04, 0.53-2.03). Clinically important and statistically significant absolute risk differences were identified only for antibiotic-impregnated catheters versus standard catheters (-2.15%, 95% CI -4.09 to -0.20; number needed to treat [NNT] 47, 95% CI 25-500) and antibiotic-impregnated catheters versus heparin-impregnated catheters (-1.98%, -3.90 to -0.06, NNT 51, 26-1667). Nine children (2%) in the standard central venous catheter group, 14 (3%) in the antibiotic-impregnated group, and 8 (2%) in the heparin-impregnated group had catheter-related adverse events. 45 (8%) in the standard group, 35 (8%) antibiotic-impregnated group, and 29 (6%) in the heparin-impregnated group died during the study. Antibiotic-impregnated central venous catheters significantly reduced the risk of bloodstream infections compared with standard and heparin central venous catheters. Widespread use of antibiotic-impregnated central venous catheters could help prevent bloodstream infections in paediatric intensive care units. National Institute for Health Research, UK.

Catheter Related Bloodstream Infection in Haematological Patients: A Prospective, Randomized Study Comparing Heparin-Coated with Chlorhexidine and Silver Sulfadiazine Impregnated Central Venous Catheters

Central venous catheters (CVCs) are widely used in patients with hemato-oncological disease for indications such as administration of chemotherapy, parenteral nutrition, blood products and monitoring of hemodynamics. CVCs are a major source of hospital-acquired infection. The National Nosocomial Infections Surveillance System reported a rate of catheter-related bloodstream infection (CRBI) of five per 1000 central catheter-days. This study was a randomized trial in which patients with nontunneled catheters were randomly assigned to heparin-coated (7 French, polyurethane, double lumen; Arrow®, USA) or chlorhexidine and silver sulfadiazine impregnated CVCs (7 French, polyurethane, double lumen; Arrow®, USA). All CVCs were placed in the subclavian vein in the operating room. CRBI was defined according to Infectious Disease Society of America guidelines. The principal investigator determined whether infections were catheter related and had no knowledge of “the assigned arm” at the time of adjudication of the reference standard definition. Before catheter insertion, laboratory prothrombotic markers included factor V Leiden, the prothrombin gene Gly20210A mutation, plasma antithrombin levels, and protein C and S activity. In our study, all patients were systematically examined by ultrasonography just before, or less than 24 hours after, catheter removal and in case of clinical signs of thrombosis. Two radiologists performed the ultrasonography and were unaware of the allocation of the patients. Two hundred and twenty patients were randomly assigned. Eight patients were excluded after assignment. Ultimately, 212 patients were analyzed [median age: 28 years (7–60); 97 female and 115 male]. CRBI occurred in 6.7% (7/104) of those in the heparin-coated group (2.7 events per 1000 days) and in 4.6% (5/108) in the chlorhexidine and silver sulfadiazine group (2 events per 1000 days) (P=0.5). The microorganisms involved in CRBIs were coagulase-negative Staphylococcus (five cases in the heparin group and 3 cases in the antiseptic group), Staphylococcus aureus (one case in the heparin group), Candida parapsilosis (one case in the antiseptic group), Pseudomonas aeruginosa (one case in the heparin group and one case in the antiseptic group). We observed a CVC-related thrombosis in 11 patients (5.2%; 5 in the heparin group and 6 in the antiseptic group P=0.8). Catheter-related thrombosis and CRBI coincided in two patients and were not significantly correlated (P=0.6). Four (1.9%) and three (1.4%) patients had evidence of protein C and protein S deficiency, respectively. Only one patient had an antithrombin deficiency (0.5%). In total, 9 patients (4.2%) were heterozygous for the factor V Leiden mutation. Thrombosis was diagnosed in three out of 17 patients (17.6%) with a inherited prothrombotic abnormality compared to 8 out of 195 patients (4.1%) who did not have a thrombophilic marker (relative risk 4.3 CI 95% 1.2–14.7). Six and five patients experienced severe bleeding in the heparin and antiseptic groups, respectively. We did not observe heparin-induced thrombocytopenia and anaphylaxis to chlorhexidine was not reported. To our knowledge, this is the first randomized study comparing in haematological patients heparin-coated with antiseptic impregnated CVCs. Furthermore, our results suggest that inherited prothrombotic abnormalities contribute substantially to CVC-related thrombosis in hemato-oncological patients. Presently, the best options for reducing CRBI are heparin-coated and antibiotic-impregnated CVCs. A large, well designed randomized controlled trial is required to determine which of these is most effective.

Effectiveness of impregnated central venous catheters for catheter related blood stream infection: a systematic review

Clinicians need information on the relative effectiveness of different types of impregnated central venous catheter for serious infection and their relative costs and adverse effects in order to decide which type, if any, to use. We systematically reviewed 37 randomized controlled trials involving 11 586 patients. Only seven studies were classified as good on all measures of study quality. Compared with standard catheters, significant and substantial reductions in catheter-related blood stream infection were found for heparin-coated and antibiotic-impregnated central venous catheters. We found no statistically significant benefits of antiseptic central venous catheters, coated with chlorhexidine and silver sulphadiazine, or sliver-impregnated central venous catheters, compared with standard catheters. The few 'head-to-head' comparisons confirmed the benefits of antibiotic impregnation compared with chlorhexidine and silver sulphadiazine or silver impregnation, but no significant difference was found for heparin-coated compared with silver-impregnated central venous catheters. No studies reported serious adverse events, but there is some evidence of antibiotic resistance from in-vitro studies. No impregnated central venous catheter exists for neonates weighing less than 3 kg, and few studies have been undertaken in larger children. The most promising options for reducing catheter-related blood stream infection are heparin-coated or antibiotic-impregnated central venous catheters. Large, high-quality randomized controlled trials are needed to evaluate which of these methods is most effective for reducing clinically important consequences of catheter-associated infection.

Infection associated with central venous or epidural catheters: how to reduce it?

Central venous catheters are a leading source of nosocomial bloodstream infection with an estimated 10% mortality. Infection associated with epidural catheterization is an uncommon but devastating complication. Diagnosis of spinal epidural abscess requires a high index of suspicion and imaging techniques such as MRI. Early diagnosis and treatment will minimize permanent damage, but primary prevention should be the aim, which depends on proper patient evaluation and use of full aseptic precautions. Recent studies suggest that epidural infection is no longer as rare a complication as once thought and may be increasing. It is not clear whether this increase is related to an increase in reporting, an overall increase in the total number of epidurals (especially extended use) being performed, or a true increase in infection rate. Implementation of multistep prevention programs has been shown to decrease central venous catheter-related bloodstream infection rate. Antiseptic or antibiotic-impregnated central venous catheters are effective in decreasing central venous catheter-related bloodstream infections. Healthcare worker education and training are essential to create standardization of aseptic care. Continuous surveillance is necessary for identifying lapses in infection-control practices.

Effect of Chlorhexidine/Silver Sulfadiazine-Impregnated Central Venous Catheters in an Intensive Care Unit with a Low Blood Stream Infection Rate after Implementation of an Educational Program: A Before–After Trial

Current guidelines recommend using antiseptic- or antibiotic-impregnated central venous catheters (CVCs) if, following a comprehensive strategy to prevent catheter-related blood stream infection (CR-BSI), infection rates remain above institutional goals based on benchmark values. The purpose of this study was to determine if chlorhexidine/silver sulfadiazine-impregnated CVCs could decrease the CR-BSI rate in an intensive care unit (ICU) with a low baseline infection rate. Pre-intervention and post-intervention observational study in a 24-bed surgical/trauma/burn ICU from October, 2002 to August, 2005. All patients requiring CVC placement after March, 2004 had a chlorhexidine/silver sulfadiazine-impregnated catheter inserted (post-intervention period). Twenty-three CR-BSIs occurred in 6,960 catheter days (3.3 per 1,000 catheter days)during the 17-month control period. After introduction of chlorhexidine/silver sulfadiazine-impregnated catheters, 16 CR-BSIs occurred in 7,732 catheter days (2.1 per 1,000 catheter days; p = 0.16). The average length of time required for an infection to become established after catheterization was similar in the two groups (8.4 vs. 8.6 days; p = 0.85). Chlorhexidine/silver sulfadiazine-impregnated catheters did not result in a statistically significant change in the microbiological profile of CR-BSIs, nor did they increase the incidence of resistant organisms. Although chlorhexidine/silver sulfadiazine-impregnated catheters are useful in specific patient populations, they did not result in a statistically significant decrease in the CR-BSI rate in this study, beyond what was achieved with education alone.

DURABILITY OF ANTISEPTIC CENTRAL VENOUS CATHETERS AS A FUNCTION OF DURATION OF CATHETERIZATION: SILVER/CARBON/PLATINUM VERSUS MINOCYCLINE/RIFAMPIN

PURPOSE: Three types of antiseptic or antibiotic impregnated central venous catheters (CVCs) are commercially available. Only one study has examined the durability of these catheters (chlorhexidine/silver sulfadiazine vs minocycline/rifampin (MR)). We hypothesized that CVCs coated with MR have a longer antimicrobial activity as a function of duration of catherization compared to silver/carbon/platinum (SPC) CVCs.

New Choices for Central Venous Catheters: Potential Financial Implications

Objective To determine the cost-effectiveness of the newer antiseptic and antibiotic-impregnated central venous catheters (CVCs) relative to uncoated CVCs and to each other. Design Decision model analysis of the cost and efficacy of CVCs coated with either chlorhexidine silver sulfadiazine (CSS) or rifampin-minocycline (RM) at preventing catheter-related bloodstream infections (CRBSIs). The primary outcome is the incremental cost (or savings) to prevent one additional CRBSI. Model estimates are derived from prospective trials of the CSS and RM CVCs and from other studies describing the costs of CRBSIs. Setting and patients Hypothetical cohort of 1,000 patients requiring placement of a CVC. Interventions In the model, patients were managed with either an uncoated CVC, CSS CVC, or RM CVC. Measurements and main results The incremental cost-effectiveness of the treated CVCs was calculated as the savings resulting from CRBSIs averted less the additional costs of the newer devices. Sensitivity analysis of the effect of the major clinical inputs was performed. For the base case analysis, we assumed the incidence of CRBSIs was 3.3% with traditional catheters and that the CSS and RM CVC conferred a relative risk reduction for the development of CRBSIs of 60% and 85%, respectively. Despite their significantly higher cost than older catheters, both novel CVCs yield significant savings. Employing either of the treated CVCs saves approximately $10,000 per CRBSI prevented (relative to standard catheters). Comparing the RM CVC to the CSS CVC revealed the RM product to be economically superior, saving nearly $9,600 per CRBSI averted and $81 per patient in the cohort. For sensitivity analysis, we adjusted all model variables by 50% individually and then simultaneously. This demonstrated the model to be most sensitive to the cost of a CRBSI; however, with all inputs skewed by 50% against both the CSS CVC and the RM CVC, these devices remained economically attractive. Under this scenario, use of either treated device was less costly. Conclusions Utilization of antiseptic and antibiotic-impregnated CVCs represent an attractive alternative for the prevention of CRBSIs and may lead to significant savings. Of the two newer, coated devices, the RM CVC performs better financially. These observations hold over a range of estimates for our model inputs. To determine the cost-effectiveness of the newer antiseptic and antibiotic-impregnated central venous catheters (CVCs) relative to uncoated CVCs and to each other. Decision model analysis of the cost and efficacy of CVCs coated with either chlorhexidine silver sulfadiazine (CSS) or rifampin-minocycline (RM) at preventing catheter-related bloodstream infections (CRBSIs). The primary outcome is the incremental cost (or savings) to prevent one additional CRBSI. Model estimates are derived from prospective trials of the CSS and RM CVCs and from other studies describing the costs of CRBSIs. Hypothetical cohort of 1,000 patients requiring placement of a CVC. In the model, patients were managed with either an uncoated CVC, CSS CVC, or RM CVC. The incremental cost-effectiveness of the treated CVCs was calculated as the savings resulting from CRBSIs averted less the additional costs of the newer devices. Sensitivity analysis of the effect of the major clinical inputs was performed. For the base case analysis, we assumed the incidence of CRBSIs was 3.3% with traditional catheters and that the CSS and RM CVC conferred a relative risk reduction for the development of CRBSIs of 60% and 85%, respectively. Despite their significantly higher cost than older catheters, both novel CVCs yield significant savings. Employing either of the treated CVCs saves approximately $10,000 per CRBSI prevented (relative to standard catheters). Comparing the RM CVC to the CSS CVC revealed the RM product to be economically superior, saving nearly $9,600 per CRBSI averted and $81 per patient in the cohort. For sensitivity analysis, we adjusted all model variables by 50% individually and then simultaneously. This demonstrated the model to be most sensitive to the cost of a CRBSI; however, with all inputs skewed by 50% against both the CSS CVC and the RM CVC, these devices remained economically attractive. Under this scenario, use of either treated device was less costly. Utilization of antiseptic and antibiotic-impregnated CVCs represent an attractive alternative for the prevention of CRBSIs and may lead to significant savings. Of the two newer, coated devices, the RM CVC performs better financially. These observations hold over a range of estimates for our model inputs.