Assessment of the anti-biofilm effect of micafungin in an animal model of catheter-related candidemia.

In cases where catheter-related candidemia (CRC) must be managed without catheter withdrawal, antifungal lock therapy using highly active anti-biofilm (HAAB) agents is combined with systemic treatment. However, the activity of HAAB agents has never been studied in in vivo models using bioluminescence. We assessed the efficacy of micafungin using a bioluminescent Candida albicans SKCA23-ACTgLuc strain in an animal model of CRC. We divided 33 female Wistar rats into five groups: sham (A), infected nontreated (B), treated with lock therapy (0.16 mg/ml) (C), systemically treated only (1 mg/kg) (D), and systemically treated+lock (E). Catheters were colonized 24 h before insertion into the femoral vein (day 0). Treatment started on day 1 and lasted 7 days, followed by 7 days of surveillance. Bioluminescence assays were carried out on days 1, 3, 5, and 14, together with daily monitoring of clinical variables. Postmortem microbiological cultures from the catheter and several tissue samples were also obtained. Overall, 28 rats (84.8%) completed the study. Group B animals showed significant weight loss at days 2, 4, and 5 compared with groups C and D (P < .05). In group B, no animals survived after day 7, 75% had CRC, and bioluminescence remained constant 5 days after catheter implantation. Positive catheter culture rates in groups C, D, and E were, respectively, 83.3%, 62.5%, and 25.0% (P = .15). Micafungin proved to be a HAAB agent when administered both systemically and in lock therapy in an animal model of CRC, although the bioluminescence signal persists after treatment. This persistence should be further analyzed.

Can Sophorolipids prevent biofilm formation on silicone catheter tubes?

Given the impact of biofilms in health care environment and the increasing antibiotic resistance and/or tolerance, new strategies for preventing that occurrence in medical devices are obligatory. Thus, biomaterials surface functionalization with active compounds can be a valuable approach. In the present study the ability of the biosurfactants sophorolipids to prevent biofilms formation on silicone rubber aimed for medical catheters was investigated. Sophorolipids produced by Starmerella bombicola, identified by HPLC-MS/MS were used to cover silicone and surface characterization was evaluated through contact angle measurements and FTIR-ATR. Results revealed that sophorolipids presence on silicone surface decreased the hydrophobicity of the material and biofilm formation of Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. Antibiofilm activity was evaluated through different methods and was more pronounced against S. aureus. Furthermore, biocompatibility of silicone specimens with HaCaT cells was also obtained. From this study it was possible to conclude that sophorolipids seem to be a favourable approach for coating silicone catheters. Such compounds may represent a novel source of antibiofilm agents for technological development passing through strategies of permanent functionalization of surfaces.

In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections.

The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment.

Performing Gram stain directly on catheter tips: assessment of the quality of the observation process.

A previous study performed in our institution showed that catheter tip (CT) staining by combining acridine orange and Gram stain (GS) before culture anticipated catheter colonization with exhaustive and careful observation by a highly trained technician. Our objective was to assess the validity values of GS without acridine orange on an external smear of CT for predicting catheter colonization and catheter-related bloodstream infection (C-RBSI). We compared different periods of observation and the results of two technicians with different levels of professional experience. Over a 5-month period, the roll-plate technique was preceded by direct GS of all CTs sent to the microbiology laboratory. The reading was taken at ×100 by two observers with different skill levels. Each observer performed a routine examination (3 min along three longitudinal lines) and an exhaustive examination (5 min along five longitudinal lines). The presence of at least one cell was considered positive. All slides were read before culture results were known. We included a total of 271 CTs from 209 patients. The prevalence of catheter colonization and C-RBSI was 16.2 % and 5.1 %, respectively. Routine and exhaustive examinations revealed only 29.5 % and 40.9 % of colonized catheters, respectively (p < 0.001). In contrast, they revealed high negative predictive values for C-RBSI (96.5 % and 96.3 %, respectively). Our study shows that the yield of GS performed directly on CTs is greater when staining is performed exhaustively. However, the decision to implement this approach in daily routine will depend on the prevalence rate of catheter colonization at each institution.

Molecular investigation of bacterial communities on the inner and outer surfaces of peripheral venous catheters.

Peripheral venous catheters (PVCs) are some of the most widely used medical devices in hospitals worldwide. PVC-related infections increase morbidity and treatment costs. The inner surfaces of PVCs are rarely examined for the population structure of bacteria, as it is generally believed that bacteria at this niche are similar to those on the external surface of PVCs. We primarily test this hypothesis and also study the effect of antibiotic treatment on bacterial communities from PVC surfaces. The inner and outer surfaces of PVCs from 15 patients were examined by 454 GS FLX Titanium 16S rRNA sequencing and the culture method. None of the PVCs were colonised according to the culture method and none of the patients had a bacteraemia. From a total of 127,536 high-quality sequence reads, 14 bacterial phyla and 268 diverse bacterial genera were detected. The number of operational taxonomic units for each sample was in the range of 86-157, even though 60 % of patients had received antibiotic treatment. Stenotrophomonas maltophilia was the predominant bacterial species in all the examined PVC samples. There were noticeable but not statistically significant differences between the inner and outer surfaces of PVCs in terms of the distribution of the taxonomic groups. In addition, the bacterial communities on PVCs from antibiotic-treated patients were significantly different from untreated patients. In conclusion, the surfaces of PVCs display complex bacterial communities. Although their significance has yet to be determined, these findings alter our perception of PVC-related infections.

Cost savings and clinical acceptability of an intravascular line tip culture triage policy.

BACKGROUND: Culture of intravascular line tips is useful for the diagnosis of intravascular line-related phlebitis and bacteraemia. However, the test lacks specificity, with a low predictive value for intravascular line bacteraemia. A recent randomised study showed that predictive value could be increased and costs reduced by refrigerating intravascular lines and retrieving them for culture only if there was a bacteraemia in the seven days before or after the intravascular line was received. AIM: We studied whether a similar triage policy could be introduced into our 1400-bed National Health Service (NHS) teaching hospital in the UK. We assessed cost reduction in the laboratory and clinical acceptability. METHODS: Data regarding the number of intravascular lines received, stored and cultured and blood cultures received was retrieved from the microbiology computer, for five-month periods before and after the introduction of the new triage policy. FINDINGS: Of the 134 intravascular line tips received in the five months after the policy had been introduced, 101 (75%) were stored without retrieval and 33 were cultured. Of these, 7/134 (5%) were culture positive and three matched a concurrent blood culture. Audit showed that compliance with the policy was >98%. The estimated annual cost reduction following the introduction of the policy was £3,166.96. The policy was acceptable to clinicians. CONCLUSIONS: The policy was both cost saving and clinically acceptable. If the policy were adopted throughout the NHS in the UK, the annual cost saving to the service might be in the order of £300,000.

Estimating the proportion of healthcare-associated infections that are reasonably preventable and the related mortality and costs.

OBJECTIVE: To estimate the proportion of healthcare-associated infections (HAIs) in US hospitals that are "reasonably preventable," along with their related mortality and costs. METHODS: To estimate preventability of catheter-associated bloodstream infections (CABSIs), catheter-associated urinary tract infections (CAUTIs), surgical site infections (SSIs), and ventilator-associated pneumonia (VAP), we used a federally sponsored systematic review of interventions to reduce HAIs. Ranges of preventability included the lowest and highest risk reductions reported by US studies of "moderate" to "good" quality published in the last 10 years. We used the most recently published national data to determine the annual incidence of HAIs and associated mortality. To estimate incremental cost of HAIs, we performed a systematic review, which included costs from studies in general US patient populations. To calculate ranges for the annual number of preventable infections and deaths and annual costs, we multiplied our infection, mortality, and cost figures with our ranges of preventability for each HAI. RESULTS: As many as 65%-70% of cases of CABSI and CAUTI and 55% of cases of VAP and SSI may be preventable with current evidence-based strategies. CAUTI may be the most preventable HAI. CABSI has the highest number of preventable deaths, followed by VAP. CABSI also has the highest cost impact; costs due to preventable cases of VAP, CAUTI, and SSI are likely less. CONCLUSIONS: Our findings suggest that 100% prevention of HAIs may not be attainable with current evidence-based prevention strategies; however, comprehensive implementation of such strategies could prevent hundreds of thousands of HAIs and save tens of thousands of lives and billions of dollars.

Prospective, randomised study of selective versus routine culture of vascular catheter tips: patient outcome, antibiotic use and laboratory workload.

In order to assess the value of vascular catheter tip culture in patients with negative blood cultures, all tip samples from hospitalised patients were prospectively randomised (1:1) to two different routines for processing catheters: culture of all tips (routine A) vs culture only of tips from patients with concomitant bacteraemia or fungaemia (routine B). Over a nine-month period, 426 catheters from 318 patients were randomly assigned to routine A and 429 catheters from 322 patients to routine B (n=40 [corrected] patients). We compared the outcome and costs from both groups. No statistically significant differences were found with respect to demographic data, mortality, hospital stay or antimicrobial use. In non-bacteraemic/fungaemic cases (N=517), days on antimicrobial therapy after catheter withdrawal were significantly higher in patients from group A [10.0 days (interquartile range, IQR): 6.0-14.0] vs 8.0 days (IQR: 4.7-12.2), P=0.03], as was the number of daily defined doses (DDDs) of antimicrobials [10.8 DDDs (IQR: 2.4-26.9) vs 7.5 DDDs (IQR: 1.5-20.0), P=0.03]. Median antimicrobial cost per treated patient was significantly higher in group A: €222.30 (IQR: €20.30-€1,030.60) vs €109.10 (IQR: €10.90-€653.20), P=0.05. If all vascular catheter tips were processed according to routine B, the microbiology laboratory workload would decrease by 77% for the total number of catheters processed. Microbiology laboratories should not routinely culture catheter tips in patients without bacteraemia or fungaemia.

Medicare reimbursement policies and hemodialysis vascular access outcomes: a need for change.

In March 2010, the Center for Medicare and Medicaid Services (CMS) convened several clinical technical expert panels (C-TEP) to provide recommendations for improving various aspects of hemodialysis management. One of the C-TEPs was tasked with recommending measures to decrease vascular access-related infections. The members of this C-TEP, who are the authors of this manuscript, concluded unanimously that the single most important measure would be to remove financial and regulatory barriers to timely placement and revision of hemodialysis fistulas and the concurrent avoidance of catheter use. The following position paper outlines the financial barriers to improved vascular access outcomes and our proposals for a future CMS demonstration project.

Efficacy of trypsin in enhancing assessment of bacterial colonisation of vascular catheters.

Since the number of organisms isolated from a medical device is crucial in assessing the likelihood of device-associated infection, we examined whether incubation of catheters in trypsin before sonication can increase the yield of superficially colonised vascular catheters in vitro and those removed from patients. Polyurethane and silicone catheters were individually colonised in vitro with individual clinical isolates including Staphylococcus aureus and Escherichia coli. Equal numbers of 1 cm segments of colonised catheters were then individually incubated either in a trypsin-containing solution or a control solution without trypsin. Each solution containing the segment was then sonicated and cultured quantitatively. In the clinical arm, indwelling catheters removed from patients were also cut into 1 cm segments that were equally suspended in the trypsin-containing or control solution and then sonicated and cultured quantitatively. Trypsin-based sonication enhanced the detection of S. aureus on colonised polyurethane and silicone catheters in vitro by 14- and 30-fold, respectively (P = 0.03 and P = 0.04), and the detection of E. coli on colonised polyurethane and silicone catheters by 3- and 6-fold, respectively (P = 0.04 and P = 0.05). Compared with sonication alone, trypsin followed by sonication resulted in 10% increase in the detectability of significant colonisation of indwelling catheters removed from patients and 11% increase in the mean colony counts of colonising organisms (P = 0.04). Exposure of catheters to trypsin before sonication improves the sensitivity of sonication and enhances the accuracy of assessing significant catheter colonisation.