| Situation | Treatment |
| For patients with major comorbidities (ie, age 65 years or older, chronic pulmonary, liver, heart, or renal disease, cancer, diabetes, congestive heart failure, alcohol dependence, immunosuppression), smokers, or those who have used antibiotics within the prior three months, | Amoxicillin-Clavulanate (875 mg orally twice daily or the extended-release formulation dose at 2 g orally twice daily) plus a macrolide (ie, azithromycin, clarithromycin) (This expands the coverage to better treat beta-lactamase-producing H. influenzae, M. catarrhalis, and methicillin-susceptible S. aureus in addition to S. pneumoniae and atypical pathogens.)
Prefer macrolides over doxycycline because their use has been associated with improved outcomes in patients with more severe CAP (possibly due to their immunomodulatory effect) [23-26]. |
| For patients who have contraindications to macrolides (eg, risk for or known prolonged QTc, allergy), | doxycycline is an appropriate alternative. |
●When amoxicillin-clavulanate cannot be used (eg, due to allergy or other intolerance), a third-generation cephalosporin, such as cefpodoxime, is the r preferred alternative. As with amoxicillin-clavulanate, cephalosporins should be given in combination with either a macrolide or doxycycline. In general, patients with mild non-IgE-mediated reactions (eg, maculopapular rash) to penicillin can generally use third-generation cephalosporins safely. Patients with IgE-mediated reactions (hives, angioedema, anaphylaxis) or severe delayed reactions should generally use other agents. ( |
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| For those with structural lung disease, we further expand coverage to treat Enterobacteriaceae (eg, E. coli, Klebsiella spp) (algorithm 2) [10,22]. |
Monotherapy with fluoroquinolone (levofloxacin, moxifloxacin, gemifloxacin) is reserved for patients who cannot tolerate either of the above regimens (eg, due to IgE-mediated or severe, delayed hypersensitivity reactions to penicillin) because of its adverse effect profile and the potential of promoting fluoroquinolone resistance.
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●We have also begun to adopt lefamulin monotherapy into practice, particularly for patients without structural lung disease (eg, advanced COPD) who cannot tolerate beta-lactams and wish to avoid the potential adverse effects associated with fluoroquinolones [17,18]. However, clinical experience with lefamulin is limited, use may be limited by cost and/or availability, and it does not cover Enterobacteriaceae. Use should be avoided in patients with moderate to severe hepatic dysfunction, known long QT syndrome, or in those taking QT-prolonging agents, pregnant and breastfeeding women, and women with reproductive potential not using contraception. There are drug interactions with CYP3A4 and P-gp inducers and substrates; in addition, lefamulin tablets are contraindicated with QT-prolonging CYP3A4 substrates. Refer to the Lexicomp drug interactions tool included within UpToDate.
●Omadacycline is another newer agent that is active against most CAP pathogens, including Enterobacteriaceae. It is a potential alternative for patients who cannot tolerate beta-lactams (or other agents) and want to avoid fluoroquinolones.