Pneumonia is inflammation of the lung with consolidation. The cause of the inflammation is infection, which can be caused by a wide range of organisms. There are five classifications of pneumonia: community acquired, aspiration, hospital-acquired, ventilator-associated, and healthcare-associated. Patients who develop pneumonia in the outpatient setting and have not been in any healthcare facilities, which include wound care and hemodialysis clinics, have community-acquired pneumonia (CAP). Pneumonia can be caused by aspiration of either oropharyngeal or gastrointestinal contents. Hospital-acquired pneumonia (HAP) is defined as pneumonia that occurs 48 hours or more after admission. Ventilator-associated pneumonia (VAP) requires endotracheal intubation for at least 48 to 72 hours before the onset of pneumonia. The newest category is healthcare-associated pneumonia (HCAP), which is defined as pneumonia occuring in any patient hospitalized for at least 2 days within 90 days of the onset of the infection; residing in a nursing home or long-term care facility; received IV antibiotic therapy, wound care, or chemotherapy within the last 30 days prior to the onset of the infection; or having attended a hemodialysis clinic.
Potential complications secondary to pneumonia include further decline in pulmonary function in patients with underlying pulmonary disease, prolonged mechanical ventilation, bacteremia/sepsis/septic shock, and death.
The goal of antibiotic therapy is to eliminate the patient's symptoms, minimize or prevent complications, and decrease mortality. Use of an antimicrobial agent with the narrowest spectrum of activity that covers the suspected pathogen(s) without having activity against organisms not involved in the infection is preferred to minimize the development of resistance.
General Approach to Treatment
Designing a therapeutic regimen for any patient with any type of pneumonia begins with three general categories of consideration:
- Patient specific factors that will impact therapy (e.g., age, renal function, drug allergies and/or drug intolerances, immune status [diabetes, neutropenia, or immunocompromised host], cardiopulmonary disease, pregnancy, medical insurance and prescription coverage, exposure to resistant organisms, and prior antibiotic exposure(s) [what agents and when]).
- The top one to three organisms likely causing the infection and resistance issues associated with each organism.
- The antimicrobials that will cover these organisms. The spectrum should not be too broad or narrow; they should penetrate into the site of infection and be the most cost effective.
Factors influencing infection from a resistant organism:
- Antimicrobial therapy in preceding 90 days
- Current hospitalization of at least 5 days
- High occurrence of antibiotic resistance in the community or in the specific hospital unit
- Immunosuppressive disease and/or therapy
Presence of risk factors for HCAP:
- Hospitalization for 2 days or more in the preceding 90 days
- Resience in a nursing home or extended-care facility
- Peritoneal or hemodialysis within 30 days
- Home wound care
- Close contact family member with MDR pathogen
State of Art
Treatment of CAP is predominantly empiric, that is, treatment is started without knowing the causative pathogen. The approach to patient care is based on the classification of patients into two broad categories, outpatient and inpatient, and then further dividing the groups by comorbid conditions and location in the hospital, respectively. These guidelines use patient-specific data along with predominant pathogen information to design appropriate empirical antimicrobial regimens.
Adult outpatient previously healthy
First-line therapeutic options for treating previously healthy adults include use of a macrolide or an azalide or doxycycline. If a patient has failed therapy with a macrolide, azalide, or doxycycline, one has to consider why the patient failed. The most common reasons are either medication adherence issues or the presence of resistance organisms.If a resistant organism is suspected, then use of one of the respiratory fluoroquinolones active against S. pneumoniae (gemifloxacin, levofloxacin, or moxifloxacin) is warranted.
Adult outpatient with comorbid conditions
The comorbid conditions that can impact therapy and outcomes in patients with CAP inlcude diabetes mellitus; COPD; chronic heart, liver, or renal disease; alcoholism; malignancy; asplenia; and immunosuppressive condition or use of immunosuppressive drugs. If the patient did not receive antibiotics in the last 3 months, then either a respiratory fluoroquinolone alone or a combination of an oral beta-lactam agent plus a macrolide or azalide is recommended. If the patient received an antibiotic in the last 3 months, the recommendation is to use an agent from a different class. Doxycycline is an acceptable alternative to a macrolide or azalide.
Adult inpatient not in the ICU
For patients admitted to the hospital with CAP, the severity of illness is generally increased (caused either by the organism itself or underlying comorbidities in the patient), and the pathogens are essentially the same as in the outpatient setting. Recommendations are to use either a respiratory fluoroquinolone alone or a combination of an IV beta-lactam agent plus an advanced macrolide/azalide (clarithromycin/azithromycin) or doxycycline. Therapy should be initiated in the emergency room; however, due to the controversy with a first antibiotic dose time of less than 4 or 8 hours, no recommendations have been made regarding time to the first antibiotic dose. Conversion to oral therapy should occur when the patient is hemodynamically stable, improving clinically, and able to take oral medications, which often is within 48 to 72 hours for most patients. Discharge from the hospital should be as soon as the patient is stable and without other medical complications. The need to observe the patient in the hospital on their oral antibiotic is not necessary.
Adult inpatient in the ICU
Patients admitted to the ICU have severe pneumoniae, and the likely etiology includes S. pneumoniae and H. influenzae as in the other categories; however, the incidence of L. pneumophila increases in this setting and should be considered a potential pathogen. In addition, enteric gram-negative bacilli and S. aureus are more frequently the cause of the pneumonia in these apteints. The recommendations are to treat with an IV beta-lactam plus either azithromycin or a respiratory fluoroquinolone. This combination therapy minimizes the risk of treatment failure due to resistant pathogen as well as provides coverage against all of the potential pathogens.
Anaerobes and Streptococcus spp. are the primary pathogens if a patient aspirates his or her oral contents and develops pneumonia. Antibiotics active against these organisms include penicillin G, amicillin/sulbactam, and clindamycin. If the patient aspirates oral and gastric contents, then anaerobes and gram-negative bacilli are the primary pathogens.
Empirical selection of antimicrobial therapy for ventilator-, healthcare-, and hospital-associated pneumonia is broad spectrum; however, once culture and susceptibility information are available, the therapy should be narrowed to cover teh identified pathogen(s). Two factors important to the empirical selection of antibioics for these types of pneumonia are onset time after admission and risk factors for MDR organisms. If it is early onset (less than or equal to 5 days since admission), and there are no risk factors for MDR organisms, then the most frequent pathogens include S. pneumoniae, H. influenzae, methicillin-susceptible Staphylococcus aureus, and enteric gram-negative bacilli. If it is late-onset pneumonia and/or there are risk factors for MDR organisms, then the pathogen list includes P. aeruginosa, extended-spectrum beta-lactamase-producing K. pneumoniae, Acinetobacter spp., and MRSA. Empirical antibiotic selection must cover P. aeruginosa, which often then covers the other gram-negative pathogens.
Duration of Antimicrobial Therapy
The duration of therapy for pneumonia should be kept as short as possible and depends on several factors: type of pneumonia, inpatient or outpatient status, patient comorbidities, bactermia/sepsis, and the antibiotic chosen. If the duration of therapy is too prolonged, then it can have a negative impact on the patient's normal flora in the respirator and gastrointestinal tracts, vaginal tract of women, and on the skin. This can result in colonization with resistant pathogens, Clostridium difficile colitis, or overgrowth of yeast. In addition, the longer antibiotics are administered, the greater the chance for toxicity from the agent, as well as an increase in cost.
For treating adult outpatient CAP, two antibiotics are approved for a 5-day duration of therapy, levofloxacin (the 750-mg dose) and azithromycin. The recommended duration of therapy for all other therapies is 7 to 10 days. For treatment of CAP in adult patients admitted to the hospital, the duration is dependent on whether or not blood cultures were positive. In the absence of positive blood cultures, the duration of therapy is 7 to 10 days. If blood cultures were positive, the duration of therapy should be 2 weeks from the day blood cultures first became negative.
The duration of therapy cited in the literature for HCAP, HAP, or VAP ranges from 10 to 21 days. Efforts should be made to shorten the duration of therapy from the traditional 14 to 21 days to periods as short as 7 days, provided that the etiologic pathogen is not P. aeruginosa and that the patient has a good clinical response with resolution of clinical features of infection. Shortening the duration of therapy is acknowledged as beneficial because of the colonization, toxicity, and cost issues. Several studies evaluated mortality, clinical success, recurrence, or the development of resistance with shorter courses of therapy for VAP and found no differences when compared with longer courses of therapy.