Treatment of Nursing Home‐Acquired Pneumonia

Infections in nursing home patients are a major clinical problem, with an estimated 1.5 million infections occurring annually in long-term care facilities in the United States.1 Based on blood culture data (bacteremia) of infected nursing home patients, urinary tract infections (55%), pneumonia (7%–10%), and skin and soft tissue infections (7%–14%) account for the majority of infections in this setting.13 However, many reports indicate that lower respiratory infections, primarily pneumonia, are the most frequent infectious disease encountered in nursing home patients.4–6 The etiology of nursing home-acquired pneumonia (NHAP) is related to the patients’ underlying condition(s) or disease(s) and use of antibiotics. The pathogenesis of most pneumonias in the aging patient is due to aspiration of the oropharyngeal flora.7 The oropharynx of healthy older adults—which is comprised primarily of a mixture of anaerobic and aerobic bacteria (predominantly streptococci)—will become colonized increasingly with aerobic or facultative anaerobic Gram-negative bacilli (excluding Hemophilus influenzae, hereafter referred to as Gram-negative bacilli), when they enter long-term institutional settings such as a nursing home.8 Thus, it would be anticipated that Gram-negative bacilli would be major respiratory pathogens in patients with NHAP. However, the data on the accurate microbiology of NHAP are limited because (1) nursing home patients are often unable to provide reliable sputa; (2) invasive diagnostic procedures such as transtracheal aspiration (TTA) are not recommended routinely for frail, elderly patients; and (3) expectorated sputum is likely to be contaminated by the oropharyngeal flora. Nevertheless, using the limited available data from TTA or expectorated sputa (sputum that contains more than 25 white blood cells and less than 10 squamous epithelial cells per low power field on light microscopy) studies of NHAP, Streptococcus pneumoniae (pneumococcus) and Gram-negative bacilli are the two most frequently isolated pathogens. Alvarez et al6 found that in 414 cases of NHAP, 32% were caused by S. pneumoniae, and 29% were due to Gram-negative bacilli. In 22% of patients two pathogens were isolated.6 Bentley9 reported in two different studies—using TTA in one study and expectorated sputa or nasopharyngeal aspirates in the other—that the frequency of Gram-negative bacilli is approximately 20% compared to 31% for S. pneumoniae in NHAP. In 35 patients with NHAP, Garb et al10 found Gram-negative bacilli and S. pneumoniae in 86% and 26% of cases, respectively. Patients who previously received antibiotics were more likely to have Gram-negative bacilli as an etiology of their NHAP. In the study by Nicolle et al in which the method of sputum collection was not detailed, 16 (46%) of the 35 patients (22 patients provided diagnostic specimens) had Gram-negative bacilli compared to 6 patients (17%) with S. pneumoniae. In a recent report by Marrie et al11 on 131 NHAP cases, only 41% had a specific etiology determined. Of these diagnosed cases, 9 patients had S. pneumoniae and 11 patients had Gram-negative bacilli. In nearly all of the above studies, Klebsiella sp. was the dominant Gram-negative bacilli. What should then be the most rational approach to antimicrobial therapy of NHAP? Optimally, the initial therapeutic decision should be based on the patient's clinical status and history of previous adverse drug reactions and results from Gram stain of a reliable specimen of the lower respiratory tract secretions. However, in the majority of instances (50%–75% of patients), accurate microbiological data will not be available. Initial treatment decisions on antibiotic selection will then be empiric, based on the most likely etiological pathogen(s) in NHAP. S. pneumoniae and Gram-negative bacilli would be the two most important etiological considerations based on the data currently available. Other pathogens to consider include H. influenzae (especially in patients with chronic obstructive lung disease), Staphylococcus aureus, and various hemolytic streptococci.4,6,9,10 Empiric therapy should begin with a broad-spectrum drug regimen either as monotherapy or combined antibiotics that have antibacterial activity against S. pneumoniae, Gram-negative bacilli (especially Klebsiella sp.), H. influenzae, S. aureus, streptococci, and perhaps anaerobic bacteria. Antibiotic regimens that appear to be appropriate include second generation cephalosporins (eg cefuroxime, cefoxitin); third generation cephalosporins (eg ceftriaxone, cefoperazone); ticarcillin-clavulanic acid; ampicillin-sulbactam; ampicillin combined with oxacillin (or nafcillin) and aztreonam; or ciprofloxacin (or other quinolones such as ofloxacin) with or without penicillin or ampicillin. In seriously ill patients with NHAP or in those suspected of having Pseudomonas aeruginosa, ceftazidime plus an aminoglycoside might be one of several appropriate regimens. In this issue of JAGS, Hirata-Dulas et al12 describe a randomized study of ciprofloxacin versus ceftriaxone for treatment of NHAP. Patients were initially given intravenous ciprofloxacin (most patients received 200 mg every 12 hours) followed by the oral preparation, 750 mg every 12 hours, or intravenous ceftriaxone, 2 g every 24 hours initially followed by intramuscular ceftriaxone, 1 g every 24 hours. The clinical outcome was similar, with 50% and 54% of patients in the ciprofloxacin-treated and ceftriazone-treated group, respectively, experiencing improvement or resolution of the manifestations of pneumonia after 14 days of therapy. Prior to this study ciprofloxacin has been used to treat pneumonias in only a small number of older patients, with good success and relatively low incidence of adverse drug effects.13,14 The pharmacology of ciprofloxacin and other quinolones has been extensively studied in this population.15 These data, along with the favorable results of ciprofloxacin in treating other serious infections in elderly patients,16,17 will position this antibiotic and other quinolones as important drugs in the future for aging adults. For patients with NHAP, the role of ciprofloxacin in the treatment of this infection will still be unclear until additional studies are done.18 Hirata-Dulas et al. correctly state in this paper that, although ciprofloxacin has a relatively high minimum inhibitory concentration against S. pneumoniae, the overall failure rate against pneumococcal pneumonia has been surprisingly low in other studies.12 Nevertheless, caution must be exercised in the use of ciprofloxacin in seriously ill patients with NHAP when S. pneumoniae has not been excluded. At this time, ciprofloxacin should not necessarily be considered the first drug of choice for NHAP. Currently, ciprofloxacin would appear to be most useful as followup oral therapy for proven or presumptive Gram-negative bacillary NHAP after parenteral therapy has been completed or as initial therapy in patients in whom beta-lactam drugs and aminoglycosides are contraindicated or undesirable.