Using Omadacycline to Treat Community-Acquired Pneumonia

Community-acquired pneumonia (CAP) is an infection in the lungs that a person has contracted outside the setting of a hospital or other health care setting.  Approximately 1.5 million Americans are hospitalized per year with this condition, making CAP the second leading reason for hospitalization in the United States (Ramirez, 2019).  CAP is characterized by a cough, sputum production, fever, dyspnea, and pleuritic chest pain (Lynn, 2017).  Several risk factors may predispose an individual to this infection.  Among those include age < 6 years and >75 years, comorbidities such as chronic obstructive pulmonary disease, viral respiratory infections that may predispose an individual to a concurrent bacterial infection, smoking or alcohol/drug abuse, and impaired airway protection that may lead to aspiration (Lynn, 2017).  CAP is also more commonly seen in individuals living in a crowded environment such as in prisons and homeless shelters, and in those who have prolonged and frequent exposures to environmental toxins such as paint or gasoline (Ramirez, 2019).

Overview of Current Therapy

Until a pathogen can be identified via sputum culture and sensitivity, treatment for CAP is generally directed by identifying the likely pathogens and beginning appropriate antibiotic therapy (Ramirez, 2019).  Some of the more common pathogens include Haemophilus influenza, Mycoplasma pneumoniae, and Streptococcus pneumoniae; these would most commonly be treated with a macrolide such as azithromycin in an otherwise healthy patient (Lynn, 2017).  In patients who have been treated with antibiotic within the past three months, are immunocompromised, or are living in area with a high incidence of macrolide-resistant infections, then a fluoroquinolone such as moxifloxacin or a beta-lactam such as amoxicillin-clavulanate would be the first treatment choice (Ramirez, 2017). 

Atypical pathogenesis of CAP may include Staphylococcus aureus, Pseudomonas aeruginosa, and other enteric gram-negative bacilli (Lynn, 2017).  Increased rates in resistance of pathogens to beta-lactams, macrolides, and first-generation tetracyclines bring a need for the development of new antibiotics (Stets, et. al, 2019).  Omadacycline, a new aminomethylcyline from the tetracycline class has been shown to be effective against resistant pathogens and “reaches high concentrations in pulmonary tissues and is active against the common pathogens that cause community-acquired pneumonia” (Stets, et. al, 2019, p. 517).

Analysis of the Study

In a phase 3double-blind, randomized trial, adults with CAP were randomly assigned to be treated with either a defined course of intravenous (IV) omadacycline or moxifloxacin (Stets, et. al., 2019).  The study group of patients were selected by the following criteria: 18 years of age or older with at least three of these four common symptoms of CAP: cough, dyspnea, purulent sputum, or pleuritic chest pain; more than one abnormal vital sign, at least one laboratory or clinical finding of CAP, radiologic evidence of pneumonia, and were classified as a Pneumonia Severity Index (PSI) of II, III, or IV (Stets, et. al., 2019).  Patients were excluded if they had already undergone antibiotic therapy for CAP in the past 72 hours, had an infection that could not be classified as CAP, were immunocompromised or demonstrated renal insufficiency or hepatic disease (Stets, et. al., 2019).

Patients were randomly and evenly divided.  Both groups received treatment that lasted 7-14 days.  One group received omadacycline 100mg intravenously (IV) every 12 hours for two doses, then 100mg IV every 24 hours with an option to transition to omadacycline 300mg orally every 24 hours after three days of treatment (Stets, et. al., 2019).  The other group received moxifloxacin 400mg IV every 24 hours with the option to transition to moxifloxacin 400mg orally every 24 hours after three days of treatment (Stets, et. al, 2019). 

Efficacy of the trial was assessed in both primary and secondary end points.  The primary efficacy was assessed at 72-120 hours after the initial dose of the trial drug based on the examiner’s definition of CAP symptoms being absent, mild, moderate, or severe (Stets, et. al, 2019).  An early clinical response was defined as improvement (ex. severe to moderate or moderate to mild) from baseline in at least two or more CAP symptoms without worsening in one or more symptoms (Stets, et. al., 2019).  Secondary efficacy was assessed by observing clinical response/resolution of symptoms at end-of-treatment to the extent that further antibiotic therapy was no longer needed (Stets, et. al., 2019). 

The strengths of the trial included extensive microbiologic testing and the exclusion of patients with PSI risk of I or II as they do not routinely require hospitalization for the treatment of CAP (Stets, et. al., 2019).  Patients with PSI of V were also excluded to minimize falsely elevated morbidity during the trial (Stets, et. al., 2019). 

Noted adverse effects were seen in 41.1% of the patients treated with omadacycline and 48.5% of the patients treated with moxifloxacin (Stets, et. al., 2019).  These included gastrointestinal complaints such as abdominal pain and diarrhea in 10.2% of patients treated with omadacycline and 18.0% of those treated with moxifloxacin (Stets, et. al., 2019).  Interestingly, 2.1% of the patients treated with moxifloxacin developed Clostridium difficile infection, while no patients treated with omadacycline developed this complication (Stets, et. al., 2019).  There were a total of 12 patient deaths during the trial; these patients were older than 65 years of age and suffered from new infection during treatment, or had underlying comorbidities such as cardiovascular disease or cancer (Stets, et. al., 2019).

Study Results

“The efficacy of once-daily omadacycline, administered intravenously with the option to transition to oral administration, was noninferior to that of moxifloxacin for the treatment of hospitalized adults who had community-acquired bacterial pneumonia in the analysis of the primary end point of early clinical response” (Stets, et. al., 2019, p. 525).  The outcome and evaluation of the patient response to both omadacycline and moxifloxacin were very similar, so the choice of which antibiotic to use may come down to cost to the patient and individual insurance coverage.  A cost-comparison study by LaPensee, Lodise, and Mistry (2019) of omadacycline versus traditional antibiotics in the treatment of CAP show a there may be an initial 3-year increase of cost of treatment noted, but the “results of the scenario analyses suggest that it may be worthwhile to consider using omadacycline as a potential measure to shorten or avoid hospital stay, and thus reduce hospital costs, due to its therapeutically equivalent IV and oral formulations in appropriate patients when other oral antibiotics may not be an appropriate option for them” (para. 23). 

Case Study

I chose to use the case study presented in workshop four of Advanced Pharmacology PYC-612 for this assignment.  Although this patient has several problems than can be addressed using a SOAP note, I will only be addressing the problem “pneumonia” specific to the pharmacologic care of prescribing omadacycline in SOAP format in this paper.  The following is taken directly from “Case Information” from 4.4 Dropbox (misspellings have been corrected):

CC:  L.F. is a 20-year-old male college student with a 2-week history of cough and increased sputum production who presents to your clinic with new chest pain when he coughs, shortness of breath, intermittent fever and chills and blood-tinged sputum.

HPI: Cough treated with guaifenesin with dextromethorphan obtained from roommate

Allergies:  sulfa (nausea)

Physical examination:
GEN:  DOE and pleuritic chest pain
VS:  BP 120/75   HR 95   T 100.5   RR 35 WT 90kg   HT 6’4″
CHEST:  LUL is CTA with significantly decreased breath sounds.  There are E-to-A changes in the LLL and across the middle of the right lung field.
COR:  tachycardic, no MRG
HENT:  WNL
ABD:  WNL
GU:  WNL
NEURO:  WNL
SKIN:  WNL

Chest X-ray: Consolidation of the inferior segments of the LLL.  Remainder of the lungs are clear.  Heart size WNL.

Sputum Gram Stain:  many WBC, few epithelial cells, moderate gram-positive cocci in chains and pairs.

Conclusion

Overall, omadacycline is comparable to moxifloxacin in the treatment of CAP.  The side effects from the use of both oral and IV omadacycline are mild to moderate and are no more worrisome than those of moxifloxacin.  Long-term studies have not yet been conducted on the use of omadacycline, and future cost-comparison studies will need to be evaluated for best economical choice for treatment of CAP.

References

• Condo, K. (2018). Advanced pharmacology PYC-612 [Supplemental Material Document]. Retrieved from https://brightspace.indwes.edu/d2l/lor/viewer/view_private.d2l?ou=71782&loIdentId=35
• Edmunds, M.W. & Mayhew, M.S. (2014). Pharmacology for the primary care provider. (4^th ed.). St. Louis, MO: Elsevier.
• LaPensee, K., Lodise, T., & Mistry, R. (2019). Budget impact of omadacycline for the treatment of patients with community-acquired bacterial pneumonia in the United States from the hospital perspective. Retrieved from http://www.ahdbonline.com/issues/2019/february-2019-vol-12-no-1-supplement-1-budget-impact-of-omadacycline-for-the-treatment-of-patients-with-community-acquired-bacterial-pneumonia-in-the-united-states-from-the-hospital-perspective/2689-budget-impact-of-omadacycline-for-the-treatment-of-patients-with-community-acquired-bacterial-pneumonia-in-the-united-states-from-the-hospital-perspective
• Lynn, S. J. (2017). Community-acquired pneumonia; With accurate diagnosis, patients can be appropriately treated in and out of the hospital. American Nurse Today 12(12), pp. 6-11. Retrieved from http://web.b.ebscohost.com/ehost/pdfviewer/pdfviewer?vid=13&sid=0a5db519-98ab-46e5-b63b-0c77ce1ee4f1%40pdc-v-sessmgr06
• Omadacycline. (2019). In Epocrates (Version 19.2). [Mobile Application Software]. Retrieved from http://epocrates.com/mobile/iphone/essentials
• Ramirez, J. A. (2018). Overview of community-acquired pneumonia in adults. In File, T. M., & Bond, S (Eds.), UpToDate. Retrieved from https://0-www-uptodate-com.oak.indwes.edu/contents/overview-of-community-acquired-pneumonia-in-adults?search=community%20aquired%20pneumonia&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
• Stets, R., Popescu, M, Gonong, J. R., Mitha, I., Nseir, W., Madej, A., … Loh, E. (2019). Omadacycline for community-acquired bacterial pneumonia. The New England Journal of Medicine, 380(6), pp. 517-527.