Novel And Emerging Strategies
It is widely accepted that inappropriate and excessive antibiotic use has contributed to the emergence of increasing numbers of drug-resistant bacteria (Bosso 2011; Pinzone 2014; Roca 2015). Researchers in one extensive study found that approximately 25% of all Streptococcus pneumoniae samples were multidrug resistant, while another study found that more than 50% of Staphylococcus aureus samples isolated from patients with infections including pneumonia were multidrug resistant (Thornsberry 2008; Aliberti 2013). In regions with high antibiotic prescribing rates, resistant strains of Streptococcus pneumoniae are more common (Hicks 2011). The rising presence of resistant strains poses treatment challenges as well as public health dangers (Bosso 2011; Roca 2015).
The goal of antibiotic stewardship is to maximize beneficial clinical outcomes while minimizing negative and unintentional consequences of antimicrobial use. Adverse effects that judicious antimicrobial use may minimize include Clostridium difficile infections and multidrug-resistance (Dellit 2007; Barlam 2016).
A review of 14 scientific papers examining the application of the principles of antimicrobial stewardship in community-acquired pneumonia found an increase in appropriate antimicrobial use and a reduction in unnecessary antimicrobial prescribing. This was associated with better patient outcomes, including reduced 30-day and in-hospital mortality, shorter hospital stays, and reduced treatment failure rates and healthcare costs. A decrease in antimicrobial resistance was also observed (Bosso 2011).
Another strategy that is gaining attention is the use of shorter courses of some antibiotics in appropriate situations. Minimizing exposure to antibiotics may reduce the risk of inducing resistance (Rubinstein 2013). Short courses ranging from three to seven days have been found to be as effective for treating community-acquired pneumonia as a traditional 10-day course, but with lower risk of antibiotic-related adverse effects. This strategy also holds promise to decrease the risk of emergence of treatment-resistant organisms (Pinzone 2014).
Aspirin interacts with omega-3 fatty acid metabolic pathways to promote the formation of specialized inflammation-resolving molecules called “resolvins.” Resolvins and related molecules appear to be involved in the resolution of inflammatory conditions such as pneumonia (Serhan 2004; Oh 2011; Arita 2005). An animal model suggested that an aspirin-triggered resolvin exerts antibacterial activity in a model of pneumonia and could complement antibiotic therapy (Abdulnour 2016). A study on 1005 pneumonia patients admitted to a hospital in Italy with community-acquired pneumonia showed that those who were chronic aspirin users were about half as likely to die within 30 days of hospital admission as those not taking aspirin (Falcone 2015).
One serious complication of severe pneumonia is acute coronary syndrome, which occurs when the heart does not get enough blood flow (AHA 2015). One randomized open-label study enrolled 185 pneumonia patients upon hospital admission. Ninety-one of the participants received aspirin, while 94 served as a control group. The rate of acute coronary syndrome in the control group during the 30 days following admission was 10.6%, while the corresponding rate in the aspirin-treated group was only 1.1%. In addition, the aspirin recipients were significantly less likely to die from cardiovascular causes (Oz 2013).
In keeping with the goal of reducing antibiotic use, non-antibiotic treatments for pneumonia are an area of active investigation. The use of statins, a class of cholesterol-lowering medication, has been associated with decreased risk of pneumonia and pneumonia-related death, as well as reduced rates of acute bacterial infections (Nassaji 2015; Lin, Chang 2016; Cheng 2014; Terblanche 2007). Statins appear to inhibit lung inflammation through modulation of neutrophil activity, inhibition of inflammatory cytokines such as nuclear factor-kappa B, and induction of an enzyme that limits oxidative stress. One study evaluated the association between statin use and efferocytosis, an inflammation-resolving process involved in recovery from pneumonia, in 22 community-acquired pneumonia patients in London. This study found that statin use was associated with higher rates of efferocytosis, an effect that was most prominent in smokers (Wootton 2016). Also, community-acquired pneumonia is associated with an increased risk of cardiovascular events, and individuals taking statins may have some protection from this risk. Further studies will be required to clarify the potential role of statins in preventing and treating pneumonia and its complications (Troeman 2013; Feldman 2015).
Blood Procalcitonin Testing to Guide Antibiotic Therapy
Elevated blood levels of a protein called procalcitonin are suggestive of a bacterial infection (Musher 2012). Along with consideration of the patient’s clinical status, measuring procalcitonin levels may help guide antibiotic therapy decisions in patients with community-acquired pneumonia (Pinzone 2014; Montassier 2013). One analysis suggested that using procalcitonin testing to determine if antibiotics should be administered reduced total antibiotic exposure and duration of antibiotic treatment (Christ-Crain 2006). Another analysis showed that procalcitonin-guided antibiotic prescribing to patients with respiratory infections, including pneumonia, reduced the median duration of antibiotic exposure by half (Schuetz 2012).