MOLECULAR DIAGNOSTICS :: ANTIMICROBIAL RESISTANCE
Figure 1.1
nosocomial infections and ventilator-associated pneumonia (VAP) mortality rates range from 20% to 60%.7 As such, a number of recent studies have examined best practices for antibiotic stewardship when it comes to lower respiratory tract infections and found inappropriate initial antimicrobial therapy is associated with increased mortality in patients with pneumonia. Historically, providers prescribed long durations of antibi-
otics for pneumonia because of concerns that short courses could lead to disease relapse or progression.8
Recent studies,
including multiple randomized controlled trials and systematic reviews, have demonstrated that shorter antibiotic therapy is safe and equally effective for most patients with pneumonia, avoiding longer antibiotic treatment that puts patients at risk for antibiotic-associated adverse events, C. difficile infection, and multi-drug resistant organisms (MDROs).8
That same
study found that more than two thirds (67.8%, 4,391/6,481) of patients received excess antibiotic therapy duration, largely due to excessive prescribing at discharge.8 A study7
published in 2021 assessing antibiotic de-escalation
in patients with nosocomial pneumonia showed that more de- escalations occurred when diagnostic tests were ordered; and importantly, in these patients de-escalation was associated with fewer antibiotic days (mean 9 vs. 11), reduced episodes of C. diff infection (2.2% vs. 3.8%) and shorter hospital days (mean 20 vs. 22 days), shorter ICU stays, less time on ventilator, reduced acute kidney injury (AKI) and reduced initiation of renal replacement therapy.7
Moreover, there was no difference
in in-hospital mortality, 14-day all-cause mortality, readmission for any indication, or treatment re-escalation in patients who received de-escalation versus no de-escalation These studies demonstrate that excess antibiotic treatment is not associated with lower rates of any adverse outcomes (that is, death, readmission, emergency department visit, or C. diff infec- tion). In fact, each excess day of antibiotic therapy is associated with 5% increased odds of experiencing an antibiotic-associated
24 DECEMBER 2022
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adverse event, and an estimated 1.03-fold increase in the odds of AMR associated with each additional day of antibiotics.
Testing methodologies For LRTIs and other infections, microbiological cultures are widely used as the standard of care for identifying the pres- ence of pathogens, and empirical broad-spectrum antibiotic therapy is initiated while waiting for the results. Limitations of microbiological cultures are well-acknowledged. These limita- tions are attributable to results taking several days, as well as factors such as dependence on microbial growth, growth being affected by sample transport time and temperature, or being inhibited by prior antibiotic treatment, contributing to sensitivity challenges. These limitations further confound the diagnostic picture in patients undergoing a long-term hospital or ICU stay for whom clinicians usually order subsequent cultures at multiple intervals throughout a patient’s stay. Alternative testing approaches can support antibiotic steward- ship and limit the use of broad-spectrum antibiotics. Multiplex molecular diagnostic panels offer a rapid and complementary approach for identifying pathogens and AMR markers. Yet many question if these panels are appropriately sensitive and suitable for reliable, accurate testing. A recent study9
examined serial microbiological culture
samples taken from hospitalized COVID pneumonia patients by comparing the results of a culture to a multiplex PCR lower respiratory panel for detection of pathogens from serial speci- mens collected from the same patient. Serial specimen analysis demonstrated that the multiplex Unyvero PCR panel was not only as accurate at detecting a pathogen, but in some cases, even more precise. Additional pathogens detected by the PCR panel could be confirmed in many instances by culture positivity for the same organism in another sample obtained from the same patient. This publication highlights the ability of the multiplex lower respiratory panel in detecting potential pneumonia pathogens earlier than culture or very early during an infection.
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