Researchers Identify Risk Factors for Antibiotic Failure Among Pneumonia Patients

The results of a recent study have shown that 22.1% of adult patients with community-acquired pneumonia who are treated in the outpatient setting do not respond to initial treatment. The research team, led by James A. McKinnell, MD, assistant professor of medicine at the David Geffen School of Medicine at University of California, Los Angeles, member of LA BioMed, and an infectious disease specialist, presented their findings at the 2017 American Thoracic Society International Conference.

In their study, the researchers note that pneumonia is the leading cause of death among all infectious diseases in the country. Of those adults who are infected with community-acquired pneumonia, approximately 1 in 4 (22.1%) need more antibiotic treatment than initially prescribed due to the failure of initial treatment, end up becoming hospitalized, or require “emergency room evaluation” during the course of their infection. The only currently available guidelines on the treatment of community-acquired pneumonia were released in 2007 by the American Thoracic Society and the Infectious Disease Society of America.

Dr. McKinnell and his team created this study with two aims: to fill the gap left by the lack of “real-world,” large-scale data, which is needed to understand why antibiotics fail to treat infection in some individuals; and to identify ideal antibiotic choices for best treatment outcomes. In a press release, Dr. McKinnell commented on the consequences of administering additional antibiotic therapy, stating, “The additional antibiotic therapy noted in the study increases the risk of antibiotic resistance and complications like [Clostridium] difficile infection, which is difficult to treat and may be life-threatening, especially for older adults.”

The study included data on 251,947 adults who presented with community-acquired pneumonia between 2011 and 2015. The average age among patients included in the study was 52.2 years, with 21.5% enrolled in Medicare. Of the patients, 52.3% were female. Patients included in the study were treated with either beta-lactam, macrolide, tetracycline, or fluoroquinolone antibiotics.

Treatment failure (TF) was defined as one of the following: getting a refill on the originally prescribed antibiotics, which accounted for 20.6% of all TFs identified among study patients, switching from one antibiotic to another 70.7%, hospitalization 5.4%, or visiting the emergency room after 30 days of receiving the first antibiotic for said infection, 3.3%.

Among those study patients in whom antibiotic treatment failed, the researchers reported that factors such as comorbidities, advanced age, and gender put patients at risk for TF. The authors wrote, “Various comorbidities were associated with higher rates of antibiotic failure including: hemiplegia/paraplegia (OR=1.33 [1.17-1.51]), rheumatologic disease (OR=1.28 [1.21-1.35]), chronic pulmonary disease (OR=1.25 [1.21-1.29]), cancer (OR=1.14 [1.09-1.18]), diabetes (OR=1.07 [1.04-1.10]) and asthma (OR=1.05 [1.01-1.10]). With each increasing Charlson Comorbidity Index (CCI) score, the probability of antibiotic failure increased (OR=1.16 [1.13-1.20] for CCI=1, OR=1.22 [1.18-1.26] for CCI=2, OR=1.44 [1.39-1.49] for CCI ?=3) compared to CCI=0.”

When the researchers categorized the outcomes of the TF group by drug class, they found that, the highest rate of TF was in the group of patients treated with beta-lactams, which accounted for 25.7% of the total TFs, followed by macrolides (22.9%); tetracyclines (22.5%); and flouroquinolones (20.8%).

The researchers also found “substantial regional variations in treatment outcomes,” which is not addressed in currently available guidelines. In addition, the study results showed that treatment for many patients who presented with comorbidities, such as cancer, diabetes, or chronic obstructive pulmonary disease, did not match guideline recommendations.

Dr. McKinnell concluded, “Our findings suggest that the community-acquired pneumonia treatment guidelines should be updated with more robust data on risk factors for clinical failure… Our data provide numerous insights into characteristics of patients who are at higher risk of complications and clinical failure. Perhaps the most striking example is the association between age and hospitalization: Patients over the age of 65 were nearly twice as likely to be hospitalized compared to younger patients when our analysis was risk adjusted, and nearly three times more likely in unadjusted analysis. Elderly patients are more vulnerable and should be treated more carefully, potentially with more aggressive antibiotic therapy.”