A Two-year review of the use of film array in a tertiary hospital in the Philippines

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. If not recognized early and managed promptly, it can lead to septic shock, multiple organ failure and death. Any type of infectious pathogen can potentially cause sepsis. Antimicrobial resistance is a major factor determining clinical unresponsiveness to treatment and rapid evolution to sepsis and septic shock. Sepsis patients with resistant pathogens have been found to have a higher risk of hospital mortality [1]. By shortening the time to pathogen identifi cation and allowing for detection of organisms missed by blood culture, new molecular methods may provide clinical benefi ts for the management of patients with sepsis [2]. Antimicrobial Resistance (AMR) threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. Patients with infections caused by drug-resistant bacteria are at increased risk of worse clinical outcomes and death, and consume more health-care resources than patients infected with non-resistant strains of the same bacteria [3].


Introduction
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. If not recognized early and managed promptly, it can lead to septic shock, multiple organ failure and death. Any type of infectious pathogen can potentially cause sepsis. Antimicrobial resistance is a major factor determining clinical unresponsiveness to treatment and rapid evolution to sepsis and septic shock. Sepsis patients with resistant pathogens have been found to have a higher risk of hospital mortality [1]. By shortening the time to pathogen identifi cation and allowing for detection of organisms missed by blood culture, new molecular methods may provide clinical benefi ts for the management of patients with sepsis [2]. Antimicrobial Resistance (AMR) threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. Patients with infections caused by drug-resistant bacteria are at increased risk of worse clinical outcomes and death, and consume more health-care resources than patients infected with non-resistant strains of the same bacteria [3]. this because molecular testing provides higher sensitivity and specifi city and, in most cases, a shorter turnaround time than traditional methodologies. For example, while conventional culture and susceptibility testing may require 72 hours to produce results, multiplex PCR assays can do so in 1 to 3 hours after the blood culture is fl agged as positive by the blood culture instrument. Benefi ts from this rapid testing will be realized if therapeutic decisions are made as soon as results are available; therefore, support from an antimicrobial stewardship team is paramount to achieve the goals of cost-effective testing and improved patient outcomes [5]. Detecting causative organism and ruling out infectious etiology remain the most critical aspect for management and prognosis of patients with suspected CNS infections. In a study by Javali, et al published in PubMed entitled, "Use of multiplex PCR based molecular diagnostics in diagnosis of suspected CNS infections in tertiary care setting-A retrospective study", it was observed that there is higher detection rate of pathogens, target specifi c escalation and evidence based de-escalation of antimicrobials using Syndrome Evaluation System (SES). Institution of appropriate therapy helped reduce unnecessary use of antimicrobials [6]. Given the advantages already demonstrated by the use of multiplex PCR along with the recent developments in this technology, future applications of PCR, when possible, should be aimed at constructing multiple detection systems in which a number of clinically and epidemiologically relevant pathogens (viruses, bacteria, parasites, and/or fungi) may be detected, characterized, and/or inevitably uncovered in a symptomand/or system-specifi c manner [7]. A study on the Preliminary experience with the use of Multiplex PCR System (FilmArray®) in a hospital from Argentina concluded that point of care multiplex PCR panel test might be useful in the acute care of patients with unknown infectious disease syndromes and negative standard test methods [8]. In this study, the usage of Biofi re® FilmArray® system will be described. It is approved for use by regulatory bodies for medical devices such as Food and Drug Administration (FDA), CE Marking for In Vitro Diagnostic (CE-IVD), and Therapeutic Goods Administration (TGA) certifying this multiplex PCR system that integrates sample preparation, amplifi cation, detection, and analysis. This simple system requires just 2 minutes of hands-on time, with a total run time of about an hour to assist in better patient care [9].

Results
A total of 547 tests were included for the two-year period covered by the study. Majority of the patients tested were from those aged 60 years old and above at 29.8%. Both the Gastrointestinal and BCID panels were also requested to this age group. The Respiratory panel was requested mostly to the pediatric age group aged 1 year old and below. The Meningitis Encephalitis Panel was mostly requested among those who are between 19 to 39 years old. Patients who had the panels tested were mostly males except for the Respiratory panel which had female predominance. These panels were mostly requested among inpatients at 69%. Although some outpatients are actually send-outs from patients admitted in other hospitals. Table 1 below summarizes the demographics of the patients who were included in the study.  Table 2 below. showing multiple viral pathogens. These are represented in Table 4.
Of the 20 tests which turned out positive in the Meningitis Encephalitis Panel, only one yielded multiple pathogens, while the rest yielded a single bacterial, viral, or fungal pathogen.
These are shown in Table 5.
All of the 15 positive Blood Culture Identifi cation Panels in     There is a study in the diagnostic modalities used in the diagnosis of sepsis and it mentioned that, "The main disadvantages of analyzing specimens after they have grown in culture are the delay in time and the potential bias introduced   by culture steps. Furthermore, uncultivable organisms cannot be identifi ed by these techniques [2]." There are several limitations of this study including the fact that this is a retrospective design done in a single hospital setting and done at a time when the tests were fi rst introduced.
The FilmArray results were also not compared with the conventional culture methods done, if any. This study could be extended up to such time when the clinicians are already aware of the tests. The study can also be done to compare the results of the FilmArray and the conventional culture.
The authors have no confl ict of interest with the manufacturers of FilmArray that may have infl uenced either the conduct or the presentation of the research.

Conclusion
The