CURRENT SITUATION

 The use of central venous catheters (CVCs) is an essential part of modern health care throughout the world, allowing for the administration of intravenous fluids, blood products, medications, and parenteral nutrition, as well as providing access for hemodialysis and hemodynamic monitoring. Use of CVCs is associated with the risk of bloodstream infection caused by microorganisms that colonize on the surface of the device or the fluid pathway when the device is inserted or manipulated after insertion.  [1]These serious infections, termed as Central- Line Associated Blood stream infections

( CLABSI) can result in increased morbidity and mortality rates, health care costs, prolonged hospital stay (median of 12 days in 1 study) as well as interruption of chemotherapy or other treatment, catheter removal, intravascular thrombosis, endocarditis or sepsis .[3] Additionally, 25% of patients contracting a CLABSI in the intensive care unit die, totaling upto 31,000 deaths annually in the US, and adds an additional annual healthcare cost of 9 billion USD [2] The main factors increasing the risk of disease include age, underlying diseases, past traumas, invasive therapy, past antimicrobial treatment and long-term immobilization. [4] The highest risk of such infections is associated with abdominal and thoracic surgeries. [4]

The most common life-threatening complication of vascular access is bloodstream infection caused by colonization of the implanted IVD or contamination of the catheter hub or infusate administered through the device.[5] Couagulase – negative Staphylococcus, specially Staphylococcus aureus act the main cause of contamination because colonization on the hands of medical personnel or the skin of the patient is the main source for the contamination of catheters [6].

Most of the Gram-negative bacilli causing CLBSI are non-enteric organisms acquired from the hospital environment, such as Stenotrophomonas maltophilia, Pseudomonas organisms, and Acinetobacter species.[6]Despite advances in medicine, including improved interventional techniques and better understanding of bloodstream infection pathomechanisms, central lines are still serious problems in patients with such infections. [4]

The clinical diagnosis of CLABSI is difficult because both the sensitivity for the clinical signs of inflammation at the catheter site and specificity for signs of systemic infections are low. [4] Variety of techniques for diagnosis of CLABSI have been studied including catheter sparing and non-catheter sparing methods [4] followed by quantitative or semi quantitative culturing methods. [7].(Table 1)  However, >80% of catheters withdrawn because of clinical suspicion of CLABSI are removed unnecessarily, because the culture results are negative [7]. In addition, the removal of a central venous catheter may be undesirable because of limited vascular access, and there could be serious complications and risks associated with reinsertion. [7] Conservative methods to assess catheter-tip colonization or CLABSI are an important advance and include paired quantitative blood cultures, differential time to positivity, superficial cultures of skin surrounding the portal of entry and catheter hubs, and Gram staining and the acridine orange leukocyte cytospin test [7].

 A recent analysis found that paired quantitative blood cultures were the most accurate diagnostic test, followed by quantitative blood culture through CVC and quantitative or semi quantitative catheter segment cultures. However, paired quantitative blood cultures are labour intensive and cost almost twice as much as standard blood cultures.[4] Hence, are  not routinely used in clinical practice. [7] Tests based on culturing methods are time consuming (minimum turnaround time 7-10 days), laborious and may often be hindered by unculturable strains, fastidious growth requirements of bacteria, unusual chemical reactions or by lack of previous identification. Although Gram staining of removed catheters is helpful in the diagnosis of local infections, they are substantially less sensitive than semi-quantitative or quantitative culture methods for disease diagnosis. [7]

SOLUTION

 The above pitfalls of conventional techniques demand a technique which facilitates non- invasive, accurate, rapid and sensitive identification of pathogenic bacteria causing CLABSI. Healthcare providers are therefore moving towards faster, reliable, sensitive, and non-invasive identification methods that deliver highly accurate results.

 Sequence based 16s rRNA gene identification of pathogenic bacteria is a rapid, novel method that accurately identifies pathogens responsible for Central Line associated Bloodstream infections.  The test, known as BactFast is made available in Sri Lanka by Credence Genomics for the very first time. With BactFast coming into practice, scientists will be able to identify disease causing organisms rapidly consequently accelerating the subsequent antimicrobial therapy. Not only BactFast facilitates identification of pathogens, but also it aids analysis of pathogens, helping physicians to narrow down the scope of therapy to more specific levels, focused on the elimination of disease causing organisms.

 Accounting to its rapid turnaround time of only 48 hours, BactFast is certainly a life saving approach. In contrast to time-consuming, error prone, cumbersome conventional techniques which are limited to an extremely constricted test scope, BactFast® is capable of identifying the entire spectrum of known bacteria within a single run. In addition, the test is capable of producing analytical measurements such as intragenic variation and comparative analysis.

Catheter Associated Bloodstream Infection rate in ICUs (per 1000 central line days) [8]

Table 1- Diagnosis of CLABSI using conventional methods

Methods not requiring CVC removal	Diagnostic Method	Description	Criteria for positivity	Sensitivity%	Specificity%
	Qualitative blood culture Through device	One or more blood cultures drawn through CVC	Any Growth	87	83
	Qualitative blood culture Through device	Blood cultures drawn through CVC, processed by pour-plate methods or lysis centrifugation technique	≥100 CFU/ml	77	90
	Paired quantitative blood culture	Simultaneous cultures drawn through CVC & precutaneously	Both cultures positive with CVC culture yielding 5-fold higher or more than peripherally drawn culture	87	98
	Differential time to positivity	Simultaneous cultures drawn, through CVC & precutaneously, and monitored continuously	Both cultures positive with CVC Positive ≥2h earlier than peripherally drawn culture	85	81
Methods requiring CVC removal	Qualitative catheter segment culture	Segment from removed CVC is immersed in broth media & incubated for 12-72 hours	Any growth	90	72
	Semi quantitative catheter segment culture	A 5 cm segment from removed CVC is rolled 4 times across blood agar plate and incubated	≥15 CFU	85	82
	Quantitative catheter segment culture	Segment from removed CVC is flushed or soinicated with the broth, serially diluted, plated on blood agar and incubated	≥1,000 CFU	83	87

CFU- Colony Forming Units; CRBSI- Catheter- Related Bloodstream Infection; CVC- Central venous system [7]

BactFast® provides a vast range of opportunities to resolve a number of issues that burdens the healthcare system.  Early detection of the disease helps the physicians to identify the course of therapy before the infection worsens and continuous medication procedures can minimize the disease complexity. It also helps to minimize the cost spent on antibiotics and additional medical care while reducing the tendency of developing antibiotic resistant microbial strains that could affect the patient’s life in long term. Moreover, it greatly reduces the hospital stay while decreasing the tendency of administration of non- specific drugs that could adversely affect other underlying diseases, imposing life threatening situations. With the exact etiology of CLABSI being revealed with sequenced base 16s rRNA gene analysis, significantly effective disease preventive measures as well as increased sanitary conditions can be established at Intensive Care Units, in turn reducing the prevalence rate of this deadly hospital- acquired infection.

 

Reference-

1. Joint Commission. “Preventing central line-associated bloodstream infections. A global challenge, a global perspective.” (2013).
2. Jill A. Marsteller, J. Bryan Sexton, Chun-Ju Hsiao, Christine G. Hollzmuller, Peter J. Pronovost, David A Thompson. “A multicenter, phased, cluster-randomized controlled trial to reduce Central- Line Associated Blood Stream Infections in Intensive Care Units.” Critical Care Medicine 40(11) 2012: 2933-2939.
3. Joshua Wolf, Nigel Curtis, Leon J. Worth, Patricia M. Flynn. ” Central Line–associated Bloodstream Infection in

Children: An Update on Treatment” The Pediatric Infectious Disease Journal 32(8) 2013: 905-910.

4. Jadwiga Wójkowska-Mach, Magda Baran, Rafał Drwiła, Mirosław Ziętkiewicz, Ewelina Foryciarz. “Factors influencing the occurrence of nosocomial bloodstream infections observed in thoracic and cardiosurgical postoperative care units.’’ Anaesthesiology Intensive Therapy 44: 2012;16-20
5. Cybele L. Abad, Nasia Safdar. “Catheter related bloodstream infections” Infectious Disease Special Edition.84-98
6. Ferretti, Gianluigi, et al. “Catheter-Related Bloodstream Infections, Part I-Pathogenesis, Diagnosis, and Management.” Cancer control6 (2002): 513-523.
7. Liñares, Josefina. “Diagnosis of catheter-related bloodstream infection: conservative techniques.” Clinical Infectious Diseases6 (2007): 827-829.
8. org. 2013. Infection Control Rates —. [online] Available at: http://www.unchealthcare.org/site/quality_safety/qualitymeasures/infectioncontrol [Accessed: 25 Nov 2013].