The RESPECT trial-Replacement of peripheral intravenous catheters according to clinical reasons or every 96 hours: A randomized, controlled, non-inferiority trial.

BACKGROUND: Peripheral intravenous catheters are widely used for infusion therapy. To prevent phlebitis, routine catheter replacement at 72 or 96 hours remains widely practiced. OBJECTIVE: To investigate the non-inferiority of clinically indicated peripheral intravenous catheter replacement compared with routine replacement every 96 hours to prevent phlebitis. Phlebitis severity, catheter indwelling time, and other catheter failure types were also compared. SETTING: Multi-center trial in wards at two hospitals in Sao Paulo, Brazil. DESIGN: The REplacement of PEripheral intravenous CaTheters according to clinical signs or every 96 hours (RESPECT) trial was a Randomized, non-blinded, controlled, non-inferiority trial. PARTICIPANTS: 1319 patients were enrolled with the following inclusion criteria: aged ≥18 years, expected peripheral intravenous therapy for ≥96 hours; peripheral intravenous catheters inserted in the selected wards, intensive care units, or surgical centers; and informed consent provided. Exclusion criteria were: bloodstream infection and/or sepsis, neutrophil count of ≤1000/mm3, and simultaneous use of more than one peripheral intravenous catheter. Recruitment occurred within 96 hours of peripheral intravenous catheter insertion. Randomization was performed using a computer-generated, concealed list. METHODS: As intervention, clinically indicated replacement group patients underwent peripheral intravenous catheter removal only at the end of therapy or in the presence of phlebitis, infiltration, occlusion, displacement, accidental removal, or bloodstream infection. Routine 96-h replacement group patients (control) had their catheters replaced every 96-h, unless clinical reasons required earlier replacement. The primary outcome was Phlebitis and the analyses were carried out on intention-to-treat and per-protocol bases. RESULTS: Demographic and clinical variables were similar between groups, with the exception to type of admission (p = 0.025) more frequent in clinically indicated patients and surgical on routine replacement group. Of the 1319 patients, 119 (9.0%) developed phlebitis with no between-group difference (p = 0.162); these patients used 2747 peripheral intravenous catheters, being that 134 presented phlebitis. Phlebitis/1000 catheter-days, was 14.9 in the clinically indicated group and 23.8 in the routine replacement group (p = 0.006). The survival analysis showed no significant between-group difference in the occurrence of the first phlebitis episode. CONCLUSIONS: Clinically indicated peripheral intravenous catheter replacement was not inferior to routine (96 hours) replacement regarding phlebitis occurrence, and was associated with significantly less phlebitis per 1000 days. TRIAL REGISTRATION: Registered with www.clinicaltrials.gov (NCT02568670).

Chlorhexidine gluconate or polyhexamethylene biguanide disc dressing to reduce the incidence of central-line-associated bloodstream infection: a feasibility randomized controlled trial (the CLABSI trial).

BACKGROUND: A number of antimicrobial-impregnated discs to prevent central-line-associated bloodstream infection (CLABSI) are marketed but it is unclear which disc is most effective. AIM: To investigate the feasibility and safety of comparing two antimicrobial-impregnated discs to prevent CLABSI. METHODS: A single-centre, parallel group, randomized controlled trial was conducted in a 929-bed tertiary referral hospital. Hospital inpatients requiring a peripherally inserted central catheter were randomized to chlorhexidine gluconate (CHG) or polyhexamethylene biguanide (PHMB) disc dressing group. Dressings were replaced every seven days, or earlier, if clinically required. Participants were followed until device removal or hospital discharge. Feasibility outcomes included: proportion of potentially eligible participants who were enrolled; proportion of protocol violations; and proportion of patients lost to follow-up. Clinical outcomes were: CLABSI incidence, diagnosed by a blinded infection control practitioner; all-cause bloodstream infection (BSI); and product-related adverse events. FINDINGS: Of 143 patients screened, 101 (71%) were eligible. Five (3.5%) declined participation. There was one post-randomization exclusion. Two (2%) protocol violations occurred in the CHG group. No patients were lost to follow-up. Three (3%) BSIs occurred; two (2%) were confirmed CLABSIs (one in each group) and one a mucosal barrier injury-related BSI. A total of 1217 device-days were studied, resulting in 1.64 CLABSIs per 1000 catheter-days. One (1%) disc-related adverse event occurred in the CHG group. CONCLUSION: Disc dressings containing PHMB are safe to use for infection prevention at catheter insertion sites. An adequately powered trial to compare PHMB and CHG discs is feasible.

Non-culture based diagnostics for intravascular catheter related bloodstream infections.

INTRODUCTION: intravascular catheter related bloodstream infection (IVC-BSI) is a leading cause of nosocomial infections and associated with significant morbidity and mortality. Early detection and adequate treatment of causative pathogens is critical for a favourable outcome. However, it takes significant time to receive microbiological results due to the current reference diagnostic method's reliance on microbial growth. Areas covered: This review discusses culture and non-culture based techniques for the diagnosis of non IVC-BSI and IVC-BSI, including molecular methods and biomarkers. Different diagnostic strategies are evaluated and the potential of new generation of diagnostic assays highlighted. Expert commentary: The development of additional diagnostic methods has potential to beneficially supplement conventional culture diagnosis, and molecular techniques have particular potential to fulfil this need. They would also contribute significant new knowledge on the bacterial species present on catheters that are generally missed by diagnosis using traditionally culture-dependent methods. Advances in molecular strategies, together with new biomarkers, might lead to the development of faster, more sensitive and cheaper technologies and instruments. This review aims to provide a platform for the further development of IVCBSI diagnostic techniques.

A 4-arm randomized controlled pilot trial of innovative solutions for jugular central venous access device securement in 221 cardiac surgical patients.

PURPOSE: To improve jugular central venous access device (CVAD) securement, prevent CVAD failure (composite: dislodgement, occlusion, breakage, local or bloodstream infection), and assess subsequent trial feasibility. MATERIALS AND METHODS: Study design was a 4-arm, parallel, randomized, controlled, nonblinded, pilot trial. Patients received CVAD securement with (i) suture+bordered polyurethane (suture + BPU; control), (ii) suture+absorbent dressing (suture + AD), (iii) sutureless securement device+simple polyurethane (SSD+SPU), or (iv) tissue adhesive+simple polyurethane (TA+SPU). Midtrial, due to safety, the TA+SPU intervention was replaced with a suture + TA+SPU group. RESULTS: A total of 221 patients were randomized with 2 postrandomization exclusions. Central venous access device failure was as follows: suture + BPU controls, 2 (4%) of 55 (0.52/1000 hours); suture + AD, 1 (2%) of 56 (0.26/1000 hours, P=.560); SSD+SPU, 4 (7%) of 55 (1.04/1000 hours, P=.417); TA+SPU, 4 (17%) of 23 (2.53/1000 hours, P=.049); and suture + TA+SPU, 0 (0%) of 30 (P=.263; intention-to-treat, log-rank tests). Central venous access device failure was predicted (P<.05) by baseline poor/fair skin integrity (hazard ratio, 9.8; 95% confidence interval, 1.2-79.9) or impaired mental state at CVAD removal (hazard ratio, 14.2; 95% confidence interval, 3.0-68.4). CONCLUSIONS: Jugular CVAD securement is challenging in postcardiac surgical patients who are coagulopathic and mobilized early. TA+SPU was ineffective for CVAD securement and is not recommended. Suture + TA+SPU appeared promising, with zero CVAD failure observed. Future trials should resolve uncertainty about the comparative effect of suture + TA+SPU, suture + AD, and SSD+SPU vs suture + BPU.

In situ diagnostic methods for catheter related bloodstream infection in burns patients: A pilot study.

BACKGROUND: One of the most common and potentially fatal complications in critically ill burns patients is catheter related bloodstream infection (CR-BSI). Lack of in situ diagnostic techniques requires device removal if CR-BSI is suspected with 75-85% of catheters withdrawn unnecessarily. AIMS: To assess the sensitivity, specificity and accuracy of two in situ diagnostic methods for CR-BSI in an adult ICU burns population: Differential Time to Positivity (DTP) and Semi-Quantitative Superficial Cultures (SQSC). METHODS: Both arterial (AC) and central venous (CVC) catheters were studied. On clinicians' suspicion of CR-BSI, the CVC and AC were removed. Superficial semi-quantitative cultures were taken by removing the dressings and swabbing within a 3cm radius of the CVC and AC insertion sites, as well as inside each hub of the CVC and AC. Peripheral blood was taken for qualitative culture and the catheter tip sent for semi-quantitative culture. DTP was considered positive if culture of lumen blood became positive at least 120min before peripheral blood with an identical pathogen. Superficial and tip cultures were identified as positive if ≥15 CFUs were grown. CR-BSI was confirmed when both catheter tip culture and peripheral blood culture were positive with the same micro-organism. RESULTS: Sixteen patients (88% male) with an APACHE II score of 22.0 (7.3) were enrolled. The mean age was 45.7 (16.9) years with mean total burn surface area 32.9 (19.4)%. Fifty percent had airway burns. ICU stay was 19.9 (11.1) days. All 16 survived ICU discharge with a hospital survival of 93%. There were 20 episodes of CR-BSI in these 16 patients. For these 20 episodes the exposure time (line days) was 113.15. The CR-BSI rate was 15.6 per 1000 catheter days (95% CI 1.9-56.4). For diagnosis of CR-BSI in either AC and CVC, SQSC had a sensitivity of 50% [95% CI 3-97], specificity 83.3% [95% CI 67-93], PPV 14.3 [95% CI 1-58], NPV 96.8 [95% CI 81-100], accuracy of 81.6% [95%CI 65-92] and diagnostic odds ratio 5.0 [95% CI 0.3-91.5]. To diagnose tip colonisation (>15CFU), sensitivity of SQSC was 75% [95% CI 22-99], specificity 88.2% [95%CI 72-96], PPV 42.7 [95% CI 12-80], NPV96.8% [95% CI 81-100], accuracy 86.8% [95% CI 71-95] and diagnostic odds ratio 22.5 [95% CI 1.9-271.9]. For combined DTP blood cultures, sensitivity for CR-BSI was 50% [95% CI 3-97], with specificity 97% [95% CI 82-100], PPV 50% [5% CI 3-97%], NPV 97% [95% CI 82-100], accuracy 94.3% 95% CI 79-99] and diagnostic odds ratio 32 [95% CI 1.1-970.8]. CONCLUSION: Both DTP and SQSC displayed high specificity, NPV and accuracy in a population of adult burns patients. These features may make these tests useful for ruling out CR-BSI in this patient group. This study was limited by a low number of events and further research is required.

Microbial biofilms associated with intravascular catheter-related bloodstream infections in adult intensive care patients.

Catheter-related bloodstream infection (CRBSI) is one of the most serious complications in hospitalised patients, leading to increased hospitalisation, intensive care admissions, extensive antibiotic treatment and mortality. A greater understanding of these bacterial infections is needed to improve the prevention and the management of CRBSIs. We describe here the systematic culture-independent evaluation of intravascular catheter (IVC) bacteriology. Twelve IVCs (6 central venous catheters and 6 arterial catheters) were collected from 6 patients. By using traditional culture methods, 3 patients were diagnosed with catheter colonisation including 1 patient who also had CRBSI, and 3 had no colonisation. From a total of 839,539 high-quality sequence reads from high-throughput sequencing, 8 microbial phyla and 76 diverse microbial genera were detected. All IVCs examined in this study were colonised with complex microbial communities including "non-colonised IVCs," as defined using traditional culture methods. Two main community types were observed: Enterobacteriaceae spp., dominant in patients without colonisation or CRBSI; and Staphylococcus spp., dominant in patients with colonisation and CRBSI. More diverse pathogens and a higher microbial diversity were present in patients with IVC colonisation and CRBSI. Community composition did not appear to be affected by patients' antibiotic treatment or IVC type. Characterisation of these communities is the first step in elucidating roles of these pathogens in disease progression, and to ultimately facilitate the improved prevention, refined diagnosis and management of CRBSI.

Microbial diversity on intravascular catheters from paediatric patients.

Microorganisms play important roles in intravascular catheter (IVC)-related infections, which are the most serious complications in children with IVCs, leading to increased hospitalisation, intensive care admissions, extensive antibiotic treatment and mortality. A greater understanding of bacterial communities is needed in order to improve the management of infections. We describe here the systematic culture-independent evaluation of IVC bacteriology in IVC biofilms. Twenty-four IVC samples (six peripherally inserted central catheters, eight central venous catheters and ten arterial catheters) were collected from 24 paediatric patients aged 0 to 14 years old. Barcoded amplicon libraries produced from genes coding 16S rRNA and roll-plate culture methods were used to determine the microbial composition of these samples. From a total of 1,043,406 high-quality sequence reads, eight microbial phyla and 136 diverse microbial genera were detected, separated into 12,224 operational taxonomic units (OTUs). Three phyla (Actinobacteria, Firmicutes and Proteobacteria) predominate the microorganism on the IVC surfaces, with Firmicutes representing nearly half of the OTUs found. Among the Firmicutes, Staphylococcus (15.0% of 16S rRNA reads), Streptococcus (9.6%) and Bacillus (6.1%) were the most common. Community composition did not appear to be affected by patients' age, gender, antibiotic treatment or IVC type. Differences in IVC microbiota were more likely associated with events arising from catheter dwell time, rather than the type of IVC used.

Molecular investigation of bacterial communities on intravascular catheters: no longer just Staphylococcus.

Intravascular catheter-related bloodstream infections (IVC-BSIs) are associated with significant morbidity and mortality. Culture-independent molecular approaches can reveal and capture the composition of complex microbial communities, and are now being used to reveal "new" pathogens as well as the polymicrobial nature of some infections. Patients with concurrently sited arterial and central venous catheters who had clinically suspected IVC-BSIs, were examined by the high-throughput sequencing of microbial 16S rRNA. An average of 100 operational taxonomic units (OTUs, phylotypes) was observed on each IVC, indicating that IVCs were colonised by complex and diverse bacterial communities. Ralstonia (53 % of 16S rRNA sequences), Escherichia group (16 %), Propionibacterium (5 %), Staphylococcus (5 %), and Streptococcus (2 %) were the most abundant genera. There was no statistically significant difference in the bacterial communities examined from arterial and central venous catheters; from those with and without systemic antibiotic treatment; or from conventionally colonised and uncolonised IVCs. The genome of the predominant bacteria, R. pickettii AU12-08, was found to encode resistance to antimicrobial drugs of different classes. In addition, many encoded gene products are involved in quorum sensing and biofilm formation that would further contribute to increased antimicrobial drug resistance. Our results highlight the complex diversity of microbial ecosystems on vascular devices. High-throughput sequencing of 16S rRNA offers an insight into the pathogenesis of IVC-related infections, and opens up the scope for improving diagnosis and patient management.

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.

Cyanoacrylate tissue adhesives - effective securement technique for intravascular catheters: in vitro testing of safety and feasibility.

Partial or complete dislodgement of intravascular catheters remains a significant problem in hospitals despite current securement methods. Cyanoacrylate tissue adhesives (TA) are used to close skin wounds as an alternative to sutures. These adhesives have high mechanical strength and can remain in situ for several days. This study investigated in vitro use of TAs in securing intravascular catheters (IVC). We compared two adhesives for interaction with IVC material, comparing skin glues with current securement methods in terms of their ability to prevent IVC dislodgement and inhibit microbial growth. Two TAs (Dermabond, Ethicon Inc. and Histoacryl, B. Braun) and three removal agents (Remove™, paraffin and acetone) were tested for interaction with IVC material by use of tensile testing. TAs were also compared against two polyurethane (standard and bordered) dressings (Tegaderm™ 1624 and 1633, 3M Australia Pty Ltd) and an external stabilisation device (Statlock, Bard Medical, Covington) against control (unsecured IVCs) for ability to prevent pull-out of 16 G peripheral IVCs from newborn fresh porcine skin. Agar media containing pH-sensitive dye was used to assess antimicrobial properties of TAs and polyurethane dressings to inhibit growth of Staphylococcus aureus and Staphylococcus epidermidis. Neither TA weakened the IVCs (P >0.05). Of removal agents, only acetone was associated with a significant decrease in IVC strength (P <0.05). Both TAs and Statlock significantly increased the pull-out force (P <0.01). TA was quick and easy to apply to IVCs, with no irritation or skin damage noted on removal and no bacterial colony growth under either TA.

Assessment of peripheral arterial catheters as a source of sepsis in the critically ill: a narrative review.

Intravascular devices (IVDs) are essential in the management of critically ill patients; however, IVD-related sepsis remains a major complication. Arterial catheters (ACs) are one of the most manipulated IVDs in critically ill patients. When bloodstream infection (BSI) is suspected in a patient with an IVD in situ, clinicians have focused their attention on the central venous catheter (CVC) while largely ignoring the AC. Although it would be routine for the CVC to be cultured and replaced if necessary for suspected IVD or catheter-related sepsis, the AC may not be treated in the same manner. The reasons for this may in part relate to the patient groups studied. In lower acuity patients with short dwell times, AC sepsis rates are indeed low. In the higher acuity patient, earlier studies suggested that ACs had an infective potential at least equal to short term CVCs, a finding that has translated poorly into clinical practice. It has been estimated that there may be up to 48,000 BSIs per year arising from ACs in the USA alone, suggesting a significant clinical problem. Recent evidence now shows that the infective potential of the AC is comparable with that in short term CVCs regarding both colonisation (which precedes BSI) and BSI, consolidating earlier studies. In critically ill patients suspected of catheter-related bloodsteam infection it is suggested that both the AC and CVC must now be assessed together.

The planning of rural health research: rurality and rural population issues.

Rurality and rural population issues require special consideration when planning both qualitative and quantitative health research in rural areas. The objective of this article was to explore the issues that require attention when planning the research. This is the first of two articles and focus on issues that require consideration when undertaking rural health research. The diversity of study populations, the feasibility of a research topic, the selection of a research team, and the cultural traditions of Indigenous communities, are all aspects of rural health research planning that require attention. Procedures such as identifying the characteristics of the population, the selection of measures of rurality appropriate for the research topic, the use of local liaison persons, decisions on the use of 'insider' or 'outsider' researchers, and the identification of skills resources available, increase the quality of the research outcomes. These issues are relevant to both qualitative and quantitative research. Procedures are available to address issues of particular concern in developing appropriate methods for rural health research. While we have concentrated on Australian issues and solutions, rural localities in other countries may face similar issues. Attention to rurality and rural situations when planning rural health research, results in studies that support the continued improvement of health in rural communities.

The conducting and reporting of rural health research: rurality and rural population issues.

Rurality and rural population issues require consideration when conducting and reporting on rural health research. A first article focused on the planning stage of the research. The objective of this article is to explore conducting and reporting issues that require attention when undertaking rural health research. The privacy of participants, the collection of data, the cultural traditions of Indigenous communities, the dissemination of results, and giving something back to the community, are all aspects of conducting and reporting rural health research that require attention. Procedures such as identifying the characteristics of the population, attention to safety issues when collecting data, the use of local liaison persons and acknowledging the ownership of intellectual property, increase the quality of the research outcomes. They are issues that are relevant to both qualitative and quantitative research methods. Procedures are available to address issues of particular concern in developing appropriate methods for rural health research. While we have concentrated on Australian issues, and possible solutions, rural localities in many other countries may face similar issues. In any rural setting, paying attention to issues that may affect the conducting and reporting of rural health research will hopefully result in studies that support the continued improvement of health in rural communities.

Low cefpirome levels during twice daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing.

OBJECTIVES: To measure plasma levels and pharmacokinetics of cefpirome in critically ill septic patients with normal renal function. To use the pharmacokinetic model to simulate alternate dosing regimens and identify those that predict sustained levels. DESIGN AND SETTING: A prospective, open-label, descriptive study in a 22-bed, multidisciplinary, adult ICU in a university-affiliated, tertiary referral hospital. PATIENTS: Twelve adults with normal renal function on enrollment and with suspected or documented sepsis in whom cefpirome was judged to be the appropriate therapy by the managing clinician. INTERVENTIONS: Cefpirome 2 g was infused intravenously over 3 min every 12 h. Timed blood samples were taken prior to and during two dosing intervals. Urine was collected for creatinine clearance determination. MEASUREMENTS AND RESULTS: Two patients were non-evaluable due to renal dysfunction post-enrollment. The median cefpirome trough level was 1.1 mg/l (range 0.5-8.1 mg/l) after the initial dose and 1.4 mg/l (range < 0.5-15.9 mg/l) at 'steady state'. The volumes of distribution and elimination half-lives were greater and more variable than in healthy volunteers. Pharmacokinetic simulation predicted that more frequent bolus dosing, increased doses and continuous infusions would result in concentrations greater than 4 mg/l for over 60% of the dosing interval for all patients. CONCLUSIONS: Cefpirome 2 g twice daily produced low plasma troughs in a number of patients. Our data suggest that this drug regimen may be inadequate for successful treatment of difficult-to-treat infections in critically ill patients with normal renal function.

Pharmacokinetics of ciprofloxacin in ICU patients on continuous veno-venous haemodiafiltration.

OBJECTIVES: To investigate the pharmacokinetics of intravenous ciprofloxacin 200 mg every 8 h in critically ill patients on continuous veno-venous haemodiafiltration (CVVHDF), one form of continuous renal replacement therapy (CRRT). DESIGN AND SETTING: Open, prospective clinical study in a multidisciplinary, intensive care unit in a university-affiliated tertiary referral hospital. PATIENTS: Six critically ill patients with acute renal failure on CVVHDF. INTERVENTIONS: Timed blood and ultrafiltrate samples were collected to allow pharmacokinetics and clearances to be calculated of initial and subsequent doses of 200 mg intravenous ciprofloxacin. CVVHD was performed with 1 l/h of dialysate and 2 l/h of predilution filtration solution, producing 3 l/h of dialysis effluent. The blood was pumped at 200 ml/min using a Gambro BMM-10 blood pump through a Hospal AN69HF haemofilter. MEASUREMENTS AND RESULTS: Ten pharmacokinetic profiles were measured. The CVVHDF displayed a urea clearance of 42 +/- 3 ml/min, and removed ciprofloxacin with a clearance of 37 +/- 7 ml/min. This rate was 2-2.5 greater than previously published for ciprofloxacin in other forms of CRRT. On average the CVVHDF was responsible for clearing a fifth of all ciprofloxacin eliminated (21 +/- 10%). The total body clearance of ciprofloxacin was 12.2 +/- 4.3 l/h. The trough concentration following the initial dose was 0.7 +/- 0.3 mg/l. The area under the plasma concentration time curves over a 24-h period ranged from 21 to 55 mg.h l-1. CONCLUSIONS: Intravenous ciprofloxacin 600 mg/day in critically ill patients using this form of CRRT produced adequate plasma levels for many resistant microbes found in intensive care units.