Medication Summary
The mainstay of drug therapy for bacterial pneumonia is antibiotic treatment. The choice of agent is based on the severity of the patient's illness, host factors (eg, comorbidity, age), and the presumed causative agent. Although intravenous (IV) penicillin G is currently not favored, doses in the range of 20-24 million U/d result in serum levels that exceed minimum inhibitory concentration (MIC) levels of most resistant pneumococci.
Glucocorticoids
The role of glucocorticoids in acute bacterial pneumonia is not yet clear. Classic teaching warns that the use of glucocorticoids in
infection may impair the immune response. However, findings show that local pulmonary inflammation may be reduced with systemic glucocorticoids. In the future, these drugs may be a useful adjunct in the immunocompetent patient. In one study, routine use of oral prednisone in bacterial pneumonia showed no benefit.[70]
Outpatient/inpatient antibiotic administration
Outpatients are given oral agents, and, for the most part, parenteral medications are given to admitted patients. This rationale does not preclude the clinician from giving an initial IV dose of antibiotics in the emergency department and then sending the patient home on oral agents, if the patient's condition warrants such action. The patient's condition, infection severity, and microorganism susceptibility should determine the proper dose and route of administration.
A rational approach may be to administer an oral extended-spectrum macrolide or amoxicillin and clavulanate (
Augmentin) to those with mild, outpatient disease. Oral fluoroquinolone may be substituted if a comorbidity or allergy to the first-line agents is present or for good dosing compliance. Admitted patients should receive IV therapy, a third-generation cephalosporin alone or with a macrolide. An alternative regimen would be IV fluoroquinolones.
Pediatric antimicrobial therapy
All agents discussed in the next sections are for use in persons older than 5 years. In children younger than 5 years, initial treatment of pneumonia includes IV ampicillin or nafcillin plus gentamicin or cefotaxime (for neonates), and ceftriaxone or cefotaxime can be administered as a single agent (for >28 d to 5 y). An alternative regimen includes a penicillinase-resistant penicillin plus an antipseudomonal aminoglycoside.
Outpatient treatment of mild-to-moderate pneumonias in children usually involves agents similar to those used for acute otitis media. Most of the pneumonias in these
patients probably have a viral cause. In children who have features suggesting a bacterial etiology (eg, an infiltrate on chest radiograph and/or positive findings at sputum Gram staining), the administration of antibiotics may be good clinical practice. In these cases, many clinicians begin empiric therapy with amoxicillin, but its spectrum of activity is lacking, because children in this group who do not have nonviral pneumonia usually have an infection caused by S pneumoniae and Mycoplasma species.
H influenzae type B has been less common since the introduction of the HIB vaccine. Children younger than 2 years may still be at risk for H influenzae type B infection, because their immune response is not sufficient, as it is in older children. A typical regimen for outpatient therapy may include a new macrolide agent or a second-generation or third-generation cephalosporin. Cost is a potential drawback for all agents.
Macrolides
The best initial antibiotic choice is thought to be a macrolide. Macrolides provide the best coverage for the most likely organisms in community-acquired bacterial pneumonia (CAP). Macrolides have effective coverage for gram-positive, Legionella, and Mycoplasma organisms. Azithromycin administered intravenously may be an alternative to intravenous erythromycin.
Macrolides, as a class, have the potential disadvantage of causing gastrointestinal (GI) upset. Compared with erythromycin, newer agents have fewer GI adverse effects and drug interactions, although all macrolides have the potential for drug interactions similar to those of erythromycin. Newer macrolides offer improved compliance because of reduced dosing frequency, improved action against H influenzae, and coverage of Mycoplasma species (unlike cephalosporins). The main disadvantage is cost.
Macrolides are primarily recommended for the treatment of CAP in patients younger than 60 years who are nonsmokers without comorbidity. Give special consideration to recommendations for antibiotic use in patients with comorbidity or those with CAP who are older than 60 years. Although patients in this group are still susceptible to S pneumoniae, they should receive treatment for broader coverage that includes Haemophilus, Moraxella, and other gram-negative organisms. Therefore, a prudent course of action for empiric outpatient therapy is to include: (1) one of the macrolide agents described previously plus a second- or third-generation cephalosporin or amoxicillin and clavulanate or (2) trimethoprim and sulfamethoxazole (TMP-SMZ) as a single agent.
Patients who have moderate clinical impairment or comorbidity are best treated with parenteral agents and, unless a particular agent is strongly suspected, broad coverage should be afforded. Regimens for this use include a macrolide plus a second-generation or third-generation cephalosporin, (as single agents) Ampicillin and sulbactam (Unasyn), piperacillin and tazobactam (Zosyn), or ticarcillin and clavulanate (Timentin).
Cephalosporins
Second-generation cephalosporins maintain the gram-positive activity of first-generation cephalosporins, provide good coverage against Proteus mirabilis, H influenzae, E coli, K pneumoniae, and Moraxella species, and provide adequate activity against gram-positive organisms.
Of these agents, cefprozil, cefpodoxime, and cefuroxime seem to have better in vitro activity against S pneumoniae. Second-generation cephalosporins are not effective against Legionella or Mycoplasma species. These drugs are generally well tolerated, but cost may be a factor. Oral second-generation and third-generation cephalosporins offer increased activity against gram-negative agents and may be effective against ampicillin-resistant S pneumoniae.
Third-generation cephalosporins have wider activity against most gram-negative bacteria (eg, Enterobacter, Citrobacter, Serratia, Neisseria, Providencia, Haemophilus species), including beta-lactamase–producing strains.
Intravenous cephalosporins may be combined with a macrolide agent. They broaden the gram-negative coverage, and in the case of third-generation agents, they may be effective against resistant S pneumoniae. In addition, some third-generation agents are effective against Pseudomonas, whereas second-generation agents are not.
Combination drugs
The combination of trimethoprim and sulfamethoxazole (TMP-SMZ) may be used in the patient with pneumonia and a history of chronic obstructive pulmonary disease (COPD) or smoking. It may be also used as a single agent in younger patients in whom a
Haemophilus species is the suspected agent.
TMP-SMZ is well tolerated and inexpensive. However, allergic reactions are more often associated with drugs in this class than with other antibiotics. Reactions span the spectrum from simple rash (most likely) to Steven-Johnson syndrome and toxic epidermal necrolysis (rare). Many potential drug interactions are noted.
When a severely ill patient has features of sepsis and/or respiratory failure, and/or when neutropenia is known or suspected, treatment with an intravenous macrolide is combined with an intravenous third-generation cephalosporin and vancomycin. An alternative regimen may include imipenem, meropenem, or piperacillin and tazobactam plus a macrolide and vancomycin. A fulminant course also must raise the suspicion of infection with Legionella or Mycoplasma species, Hantavirus, psittacosis, or Q fever.
Fluoroquinolones, including levofloxacin, moxifloxacin, and gatifloxacin, may also be used. These agents are available in oral and parenteral forms and have convenient dosing regimens, which allow easier conversion to oral therapy that results in good patient compliance. Note that in July 2008, a warning was issued from the US Food and Drug Administration (FDA) regarding the risk of tendonitis and tendon rupture with fluoroquinolone use