Do Patients Admitted with Community-Acquired Pneumonia Really Require IV Antibiotics?

New data suggests certain hospitalized CAP patients treated initially with oral antibiotics may not have worse outcomes compared to those initially treated with IV antibiotics.

Community-acquired pneumonia (CAP) is a relatively common disease affecting millions of individuals annually in the United States.

Despite the Infectious Diseases Society of America’s (IDSA) and American Thoracic Society’s (ATS) recently released guidelines on the management of hospital- and ventilator-associated pneumonia, the last consensus guideline on CAP management was updated nearly a decade ago.

Although the majority of CAP cases can be managed purely in the outpatient setting, approximately one-fifth of patients presenting to the emergency department require hospital admission.

Currently, the IDSA/ATS recommends treatment with either an antipneumococcal fluoroquinolone as monotherapy or a beta-lactam plus macrolide combination therapy for adults with CAP who require admission to non-intensive care unit (ICU) beds.1 Furthermore, the IDSA/ATS recommends the use of intravenous (IV) over oral fluoroquinolones for initial treatment, except in patients who lack risk factors for severe pneumonia. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) has a similar stance for the preference of IV antibiotics over PO options for initial treatment.2

Both the IDSA/ATS and the ESCMID based these recommendations heavily on a meta-analysis performed in 2004, which found no differences in mortality between non-ICU CAP patients treated with oral and IV antibiotics.3 Furthermore, patients treated with orals initially had shorter lengths of stay and lower hospital costs. However, much fewer patients were treated with orals compared with IV antibiotics and, subsequently, were more likely to be younger and have less severe diseases evidenced by lower pneumonia severity index (PSI) scores.

Despite fluoroquinolones’ having excellent bioavailability (levofloxacin ~99%, moxifloxacin ~90%), providers continue to preferentially order IV antibiotics for non-ICU patients admitted with CAP.

In general, IV medications are associated with increased injection site reactions, carry a greater nursing burden, and have a higher risk for error despite widely-used programmable smart pumps. Additionally, they’re usually associated with longer lengths of stay and have higher costs compared with their oral counterparts.

There’s a significant amount of data evaluating appropriateness of transitioning from IV to oral antibiotics, and when the proper time to do so is. However, data evaluating whether or not IV antibiotics are really necessary in the first place are lacking.

Since the 2004 meta-analysis, 2 small trials evaluated this question. The first was a small single-arm prospective trial showing high clinical response rates (96.1%) in CAP patients treated with oral gemifloxacin.4 This study, however, included both inpatient- and outpatient-treated CAP and didn’t report how many fell into each category.

The second was a small prospective trial that showed no difference in clinical efficacy of oral versus IV levofloxacin in CAP patients.5 Again, this study included a mixture of inpatients (42%) and outpatients. Subgroup analysis showed 100% clinical efficacy rates among outpatients, though only 77% among those treated as inpatients. Interestingly, further subgroup analysis was conducted comparing clinical efficacy rates among those treated with IV and oral antibiotics, showing rates of 79% and 93%, respectively. Unfortunately, it’s unknown how these rates are retained when stratifying inpatients and outpatients.

Recently, researchers compared outcomes of CAP patients who were admitted to non-ICU beds in those treated with initial oral to IV fluoroquinolones in a large retrospective cohort analysis. A total of 36,405 non-ICU CAP patients across 340 hospitals who received either moxifloxacin or levofloxacin in the emergency department or by day 1 were included in the study. Of these, just 2205 (6%) of the patients initially received oral fluoroquinolones, and the rest IV.

Most notably, levofloxacin was more common than moxifloxacin, and patients in the IV group were older and also more likely to have a principal diagnosis of sepsis, sputum or blood cultures, and blood lactate levels drawn than those in the oral group.

Intuitively, one would expect more severe patients to be initially treated with IV antibiotics, and these patients are likely at higher risk for poorer outcomes prior to the administration of antibiotics than those receiving orals. In an attempt to overcome this inherent confounding in a retrospective analysis of prescribing IV antibiotics to more severe patients, the authors used propensity scoring methods in their analyses.

After adjusting for variations in baseline characteristics with the stabilized inverse propensity treatment weighting analysis, the authors didn’t find significant differences in in-hospital mortality, length of stay, hospital cost, or escalation of care to the ICU.

Although patients who were initially given oral antibiotics were associated with a reduced risk for antibiotic escalation than those given IV fluoroquinolones, they had higher mortality rates if they did escalate to IV antibiotics. This increase in mortality wasn’t different, however, compared with those initially receiving IV fluoroquinolones.

Unfortunately, this study didn’t include CAP scoring systems such as the CURB-65 or PSI, which are commonly used by practitioners to stratify severity of disease and help guide treatment.

It appears that the IDSA/ATS recommendation of choosing initial IV antibiotics except in those with less severe disease may be substantiated by this study. Specifically, patients who are younger and don’t show signs of sepsis or organ dysfunction may not have worse outcomes if they received initial oral instead of IV antibiotics.

To truly answer this question, however, a randomized, controlled trial is required. Given that mortality from CAP is quite low, a study powered high enough to detect a meaningful difference in mortality may require a substantial number of patients, and it may not be logistically feasible.

Although the IDSA/ATS plans for the release of revised CAP guidelines in summer 2017, practitioners should critically evaluate and use new data as it’s published to guide clinical decision making as appropriate.

The views expressed in this article are those of the author and should not be attributed to the Mayo Clinic.

References

1. Mandela LA, et al. Infectious diseases society of America/American thoracic society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(suppl 2):S27-S72.

2. Woodhead M et al. Guidelines for the management of adult lower respiratory tract infections. Clin Microbiol Infect. 2011;17(suppl 6):E1-E59.

3. Marras TK, et al. Efficacy of exclusively oral antibiotic therapy in patients hospitalized with nonsevere community-acquired pneumonia: a retrospective study and meta-analysis. Am J Med. 2004;116(6):385-393.

4. Amitabh V, et al. Efficacy and safety of oral gemifloxacin for the empirical treatment of pneumonia. Lung India. 2012;29(3):248-253.

5. Mukae H, et al. Efficacy and safety of levofloxacin in patients with bacterial pneumonia evaluated according to the new “Clinical evaluation methods for new antimicrobial agents to treat respiratory tract infections (second version).” J Infect Chemother. 2014;20(7):417-422.