Examining the Surprisingly High Impact of Viruses on CAP and the Utility of Procalcitonin in Treatment Decisions

Pneumonia is the leading cause of death in children and the leading infectious killer of adults. Notable advances in our understanding of pneumonia etiology and viral infections versus bacterial infections was presented in the last session of the ASM Microbe 2017 meeting in New Orleans, Louisiana.

The sessions started with Derek J. Williams, MD, a physician-scientist with the division of Hospital Medicine at Vanderbilt University, Department of Pediatrics elaborating on the latest epidemiological and etiological studies on pneumonia. The latest epidemiological studies have revealed that viruses play a much bigger role than bacteria in causing community-acquired pneumonia (CAP) in children than was previously thought. Researchers learned about this only learned recently after development of improved molecular diagnostics.

Dr. Williams presented data from the Epidemiology of Pneumonia in the Community (EPIC) study (2015). The EPIC analysis considered 127,000 children, for which 2,300 were diagnosed by both clinical and radiographic means over the course of 2010 to 2012. Molecular examination of the children (0-17 years) revealed at least 70% of cases had a viral component. More specific etiological analysis identified Respiratory Syncytial Virus (RSV) and Human Rhinovirus (HRV) as the most common causes of CAP. Both viruses were identified in more than 25% of children. The next most common causes (10% to 15%) were adenovirus and human metapneumovirus. In addition, seasonal variations revealed a strong winter seasonal peak for RSV-associated CAP.

According to Dr. Williams it is important to remember that is much easier to identify upper as compared to lower respiratory tract infections. To this end, viruses identified by upper respiratory tract infection testing may not always reflect what is going on in the lower respiratory tract. Moreover, one must remember that 24% of asymptomatic children have a virus that is detected in their airway, while 70% of children with CAP have a detectable virus. In a subsequent presentation, Richard G. Wunderink, MD, Professor of Medicine in the Pulmonary and Critical Care Division of Northwestern University Feinberg School of Medicine and Medical Director of the MICU, Northwestern Memorial Hospital would echo this point that, stating that we do not really have a good idea of the basal bacterial and viral flora typically present in a normal healthy lung.

The EPIC study identified viruses in up to 70% of all cases of children with pneumonia. The presence of viruses was highest in children <5 years of age; they also found that it was exceptionally prevalent in adults of advanced age. In terms of specific viruses, RSV and rhinoviruses were the most prevalent cause of pneumonia, occurring in approximately 25% of cases.

Further in the presentation, Dr. Williams presented a study that showed that vaccinations protected against 59% of all influenza-associated CAP infections across all ages. Accordingly, perhaps the biggest point of Dr. William’s presentation was that they now know that the burden of viral pneumonia in children is substantial, and so there is an urgent need develop an effective vaccine for preventing common respiratory virus infections.

Switching gears to speak about how molecular diagnostics can affect pneumonia treatment decisions, Dr. Wunderink spoke about the procalcitonin test (PCT), which was just approved this year (2017) as a test for use in making important decisions regarding the optimal use of antibiotics in lower respiratory tract infections and sepsis. Dr. Wunderink reviewed the latest in pneumonia molecular diagnostics research, particularly as it is related to PCT.

During his talk, he pointed out that although both PCT and C-reactive protein are inflammatory markers positively correlating with Interleukin 6 (IL-6), only PCT is repressed by interferon (IFN)-gamma. Most importantly, PCT levels above 1.0ng/mL are indicative of a typical bacterial pneumonia infection, while PCT levels at 0.25ng/mL are likely viral, mycobacterial, or unknown.

This test could help manage antibiotic overtreatment, which is something that can increase mortality. To this end, Dr. Wunderink highlighted a study examining survival outcomes for congestive heart failure (CHF) patients with clear-cut pulmonary edema. For patients who had low PCT levels (<0.05) there was much higher rates of survival if they were not treated with an antibiotic.

Ultimately, Dr. Wunderink stressed that when you have an equivocal chest x-ray, it is clear that PCT can be very helpful. He believes it is good to avoid antibiotics in classical CHF with these equivocal chest x-rays and low grade fever. Several studies were reviewed by Dr. Wunderink that showed reduced mortality when antibiotics were used less.

“There still is no paint-by-numbers approach for treating pneumonia,” Dr. Wunderink explained. There are a variety of other considerations. Dr. Wunderink stated that he is not a big fan of using steroids for treating pneumonia, and in fact, he described a randomized controlled trial comparing the effects of steroid use in patients with CAP and high inflammatory response. There was no mortality difference in this study.

In addition, more data is emerging that indicate that there is frequently more of a cardiovascular disease component to what was otherwise previously recognized as pneumonia. Accordingly, Dr. Wunderink, adrenomedullin and troponin are worthy of greater consideration and use in estimating prognosis. Moreoever, thrombocytosis presents as an important association with significantly increased prognostic mortality.

He also stressed the importance of considering the risk for hospital-acquired infections, “For anyone of us hospitalized with pneumonia and no other underlying disease, the probability of us being alive after 1 year is very low.”

In summary, Dr. Wunderink believes PCT levels are helpful for reducing antibiotic use in patients with low risk CAP or viral pneumonia, but that it is important to understand that after a certain point, PCT is no longer a marker of viral versus bacterial, but rather it becomes a marker of general inflammation (somewhere between death and 10 days of antibiotic treatment). More work is needed to examine effects on mortality data.

W. Todd Penberthy, PhD is a medical writer with over 4 years of experience based in Orlando, Florida. Prior to that Todd was a professor directing biomedical research using zebrafish models of human disease with expertise in orthomolecular niacin-related science for 10 years.