The diagnosis and treatment of bloodstream infections remains a significant issue within the hospital environment.
Now, faster diagnosis of sepsis can optimise patient care, reduce mortality rates, shorten the length of stays, and lower hospital costs.
What is Sepsis?
Sepsis is a systemic inflammatory response to a microbial infection (including bloodstream infections such as bacteraemia and fungaemia - blood poisoning) which can lead to organ dysfunction.
It is a serious and potentially fatal condition, making prompt diagnosis and therapeutic intervention critical to facilitating effective treatment.
Identification of the causative organism has traditionally involved phenotypic analysis of organisms isolated from positive blood cultures. However, this process can take days, during which time patients may be treated with broad-spectrum antibiotics until positive pathogen identification becomes available. The scenario is further complicated by the incidence of antibiotic resistance in microbial populations, which brings additional challenges to the process of selecting the appropriate antimicrobial agent.
Faster pathogen identification is therefore very important. When a blood culture is flagged as positive a gram stain is taken that can provide an indication as to the type of organism responsible for the infection. While this is helpful, tailored therapeutic intervention relies on identification to species level, which can take a further 24-48 hours using conventional techniques.
A number of approaches have been tried to speed up this process. Biochemical assays (such as the coagulase assay used to characterise Staphylococci) are widely used but are not always completely accurate and may not provide a result for several hours. Molecular assays based on RT-PCR or nanoparticles have also come onto the market, but have a limited species range and require expensive equipment.
One of the most promising technologies to come onto the market recently has been MALDI-TOF. This versatile technique can theoretically identify any organism and has been adopted by a number of clinical microbiology laboratories. While it has proven to be effective in some cases, it has also been seen to have limitations. These include identification of organisms in the case of polymicrobial bacteraemia, and the identification of organisms with more robust cell walls such as yeasts and some gram-positive bacteria.
The QuickFISH technology is designed to identify a variety of pathogens directly from positive blood cultures in 20 minutes. This simple assay can be used as a stand-alone system in a clinical microbiology laboratory. However its adaptability and ability to identify pathogens in those situations where a MALDI-TOF system may encounter issues also makes it the ideal backup system for a MALDI-TOF.
The QuickFISH system enables a positive species identification to be obtained from a positive blood culture in just 20 minutes. This allows the pathogen identity to be reported to the clinician at the same time as the gram stain results. Providing this information permits appropriate antimicrobial therapy to commence promptly, potentially resulting in enhanced patient outcomes. In addition the ability to identify possible misleading contaminants, such as coagulase negative Staphylococci (CNS), allows treatment to be promptly de-escalated where necessary, with attendant resource savings.
- Optimise patient care
- Reduce mortality rates
- Shorten length of hospital stay
- Lower health care costs
- Reduced time to optimised antibiotic therapy
- Enhanced Pharmacovigilance: avoid unnecessary antibiotic exposure
- Decreased antibiotic costs
- Help manage the spread of antibiotic resistance
Rapid Pathogen ID Improves Patient Care, Optimises Antibiotic Use
and Reduces Medical Costs
The Impact of Septicaemia
Septicaemia is a serious illness that over the past 30 years has become increasingly common among hospitalised patients.
Caused by bacteria and bacterial toxins circulating in the bloodstream, it is the 6th most common reason for hospitalisation and is responsible for more than
266,000 deaths every year in the USA (1. Agency for Healthcare Research and Quality (AHRQ) News and Numbers, October 6, 2011)
Septicaemia, or sepsis, is the result of systemic infection by bacteria or fungi. The UK Sepsis Trust advises that sepsis claims the lives of over 37,000 individuals in the UK every year.
Survival rates correlate with the speed of delivery of appropriate antimicrobial therapy. However, without species identification prescribing the correct treatment is a challenge. Patients may be given broad spectrum antibiotics which may not be effective and contribute to the escalating problem of resistance build up. Worse still they may be given no therapy at all until the species identification is confirmed.
Traditional Gram Positive Pathogen Identification
Septicaemia is the result of systemic infection by bacteria or fungi, typically diagnosed by blood culture. Blood is taken from the patient with suspected sepsis and cultured in broth at 37C. Positive culture and Gram stain test results are usually reported within 16-24h but traditional sub-culture and identification of pathogens in positive cultures can take up to 3 more days. Patients with suspected sepsis may be prescribed empiric, broad spectrum antibiotics whilst test results are awaited but therapy may be inappropriate or ineffective. Patients may be exposed unnecessarily to high dose antibiotics or require specific antimicrobial therapy as different species of bacteria have varying profiles of antibiotic resistance.
Incidents of antibiotic resistance are increasing and a growing number of superbugs with multidrug resistance are emerging. Spontaneous or induced genetic mutations in organisms can confer resistance to antimicrobial drugs and such genes can be readily transferred between bacteria. This has led to numerous guidelines and strategies intended to contain and monitor antimicrobial resistance. A keystone of such recommendations is the appropriate use of antimicrobials. Inappropriate use of wide spectrum antibiotics increases environmental pressure on bacteria encouraging selective reproduction of resistant bacteria. In some cases, such as sepsis, empiric treatment with broad-spectrum agents is common and difficult to avoid. Specific, tailored therapy is not possible until the pathogen has been identified, but reducing delays in therapy change and minimising unnecessary exposure would be desirable.
Gram stain dilemmas
Following Gram stain positive blood cultures may be reported as Gram-positive cocci in clusters (GPCC), Gram-positive cocci in pairs and chains (GPCPC), Gram-negative rods (GNR) or Yeast.
Unfortunately this information alone is not always enough to select the most appropriate therapy. GPCC samples may indicate infection with S aureus but could also be indicative of culture contamination with Coagulase Negative Staphylococcus and not true infection. GPCPC could be E faecalis, E faecium, other Enterococci or Streptococci presenting treatment dilemmas. Whilst E Faecalis is typically susceptible to ampicillin andStreptococci generally treated with vancomycin, other species of Enterococci are both ampicillin and vancomycin resistant.
Using AdvanDx PNA FISH can rapidly resolve these and other dilemmas using multiplex identification assays. The AdvanDx QuickFISH technology can provide species identification in less than 30 minutes following Gram stain.
This means microbiology laboratories can report the species identification results together with the Gram stain call, to enable optimised therapy at the critical antibiotic decision point.
Clinicians can then prescribe the correct antimicrobial therapy for septicaemia patients much earlier and avoid unnecessary treatment for patients with CoNS contaminated blood cultures.
Earlier identification positively impacts both prognosis and length of stay, therefore improving patient care and reducing hospital costs.