Community-acquired pneumonia: Empiric antibiotic selection for adults admitted to the general medical ward*

CAP: community-acquired pneumonia; MRSA: methicillin-resistant Staphylococcus aureus; PCR: polymerase chain reaction; IV: intravenous; COPD: chronic obstructive pulmonary disease.
* This algorithm is intended for patients in whom admission to a general medical ward is considered appropriate. Refer to related UpToDate content to determine the site of care. Antibiotics should be administered as soon as possible after diagnosing CAP. If the etiology of CAP has been identified based upon reliable microbiologic methods and there is no laboratory or epidemiologic evidence of coinfection, treatment regimens should be simplified and directed to that pathogen.
¶ Individuals with a past reaction to penicillin that was mild (not Stevens Johnson syndrome, toxic epidermal necrolysis, or drug reaction with eosinophilia and systemic symptoms [DRESS]) and did not have features of an immunoglobulin (Ig)E-mediated reaction can receive a broad-spectrum (third- or fourth-generation) cephalosporin or carbapenem safely.
Δ Empiric therapy with aztreonam plus levofloxacin plus an aminoglycoside is generally appropriate for patients who warrant antipseudomonal coverage but have beta-lactam allergies that preclude the use of penicillins, cephalosporins, and carbapenems. However, patients with a prior life-threatening or anaphylactic reaction to ceftazidime should not be given aztreonam unless evaluated by an allergy specialist because of the possibility of cross-reactivity. Such patients can receive levofloxacin plus an aminoglycoside for antipseudomonal coverage in the interim.
◊ Combination therapy with a beta-lactam plus a macrolide and monotherapy with a respiratory fluoroquinolone are of generally comparable efficacy for CAP overall. However, many observational studies have suggested that beta-lactam plus macrolide combination regimens are associated with better clinical outcomes in patients with severe CAP, possibly due to the immunomodulatory effects of macrolides. Furthermore, the severity of adverse effects (including the risk for Clostridioides [formerly Clostridium] difficile infection) and the risk of selection for resistance in colonizing organisms are generally thought to be greater with fluoroquinolones than with the combination therapy regimens. For both of these reasons, we generally prefer combination therapy with a beta-lactam plus a macrolide rather than monotherapy with a fluoroquinolone. Nevertheless, cephalosporins and other antibiotic classes also increase the risk of C. difficile infection. Recent antibiotic use should also inform the decision about the most appropriate regimen; if the patient has used a beta-lactam in the prior three months, a fluoroquinolone should be chosen if possible, and vice versa.
§ Omadacycline and lefamulin are newer agents and potential alternatives for patients who cannot tolerate beta-lactams (or other agents) and want to avoid fluoroquinolones, although use may be limited by availability and/or insurance coverage.
¥ Examples of contraindications include increased risk for a prolonged QT interval and allergy.
‡ Doxycycline should not be used in pregnant women.
† The combination of vancomycin and piperacillin-tazobactam has been associated with acute kidney injury. In patients who require an anti-MRSA agent and an antipseudomonal/antipneumococcal beta-lactam, options include using a beta-lactam other than piperacillin-tazobactam (eg, cefepime or ceftazidime) or, if piperacillin-tazobactam is favored, using linezolid instead of vancomycin.
** Ceftaroline has activity against MRSA but not Pseudomonas; because of its extended spectrum, it is often reserved for patients with concern for MRSA.