Assessing and Treating Community-Acquired Pneumonia

The author explains current guidelines for determining the severity of pneumonia—always the key to successful treatment—and provides an update on the problem of antibiotic resistance, which now extends to the fluoroquinolones.

By Thomas J. Marrie, MD

A 48-year-old woman presented to the emergency department with a 48-hour history of anorexia, fever, chills, and cough and an 18-hour history of left pleuritic chest pain. Her history was significant for use of methylphenidate and acetaminophen intravenously. On examination she looked acutely ill and seemed to be confused. Her oral temperature was 102.2°F; pulse, 110; respiratory rate, 30; and blood pressure, 90/60 mm Hg. Oxygen saturation was 89%.

Crackles were present on auscultation of the left lung. Her chest x-ray showed an opacified left upper lobe, a nodular opacity in the right lower lung field, and an interstitial pattern throughout both lung fields. The interstitial pattern was present on old chest films dating back at least two years. Given the history of injection drug use, the physician examining her surmised that the interstitial pattern was most likely talc lung. He also concluded that the right lower lobe nodule represented a nipple shadow. That left only the left upper lobe opacity, which was most likely due to pneumonia.

Case example of resistant pneumonia. This 48-year-old woman presented with left-sided pleuritic pain, tachypnea, fever of 102.2°F, and other signs of serious illness. The opacity of her left upper lobe in this x-ray represented infection with S. pneumoniae that was not susceptible to penicillin. Her diffuse interstitial infiltration was ascribed to talc lung from injection drug use, and the nodular opacity in the lower right lung field was presumed a nipple shadow.

CHALLENGING PATIENT

This patient poses a number of challenges. It is evident that she is very ill. Attention has to be paid to stabilizing her respiratory and circulatory systems, and a decision needs to be made as to whether she should be transferred to a medical/surgical floor or an intensive care unit (ICU). In addition, antibiotic therapy must be started immediately. The question is, which antibiotic or antibiotics?

Two sets of blood cultures should be obtained before antibiotic therapy is started. The yield from blood cultures in patients with pneumonia ranges from 6% to 20%. If the patient can produce sputum, it should be sent for culture too. However, antibiotic therapy should not be delayed until the patient can produce sputum.

In this patient, it is important to obtain sputum for culture. Since she is an intravenous drug user, she is at risk for HIV infection and, if she is HIV-positive, she would be at a higher risk than other patients for tuberculosis and Pneumocystis carinii infection. The sputum specimen should be cultured for Mycobacterium tuberculosis in addition to the usual respiratory pathogens. If sputum can be obtained, a Gram's stain may give an immediate indication of the most likely infecting pathogen.
 

ASSESSING THE SEVERITY OF THE PNEUMONIA

The key to the successful treatment of any patient with pneumonia is an accurate assessment of the severity of the illness. The Infectious Diseases Society of America, the Canadian Infectious Diseases and Canadian Thoracic Society, and the American Thoracic Society (ATS) have all published guidelines for empirical antimicrobial therapy of community-acquired pneumonia. All three sets of guidelines use the severity of the pneumonia as the basis for selecting antibiotics. The rank order of the pathogens differs according to the severity of the pneumonia (see table below). Since the ATS guidelines are the most recent, they will be used to guide therapy for the patient presented here. However, the clinician's first task is to determine the severity of the pneumonia.

The British Thoracic Society (BTS) specifies four criteria for pneumonia severity (see box below). If none of these criteria is present, the mortality rate is 2.4%; if one is present, the rate is 8%; with two, it is 23%; with three, 33%; with four, 83%. Our patient has three of the four criteria (her urea level is not back from the laboratory yet). Thus, based on the BTS criteria, her pneumonia has a high mortality rate and she should be admitted to the ICU.

The BTS criteria are easy to remember and are therefore used most often. The ATS criteria for severe pneumonia are listed below (see box below). An oxygen saturation of 89% probably translates to a PaO₂ of less than 60 mm Hg, so our patient meets three of the four criteria and should be admitted to the ICU.

It should be kept in mind, however, that any severity of illness scoring system represents an assessment of a patient's condition at a single point in time. A patient's condition is dynamic, not static. Also, a physician must always use his or her best judgment, in addition to laboratory findings and any other available data, in making decisions as to a patient's care. Even if this patient met only two of the BTS or ATS criteria, it would be prudent to admit her to an ICU because she appears very ill clinically.

back to top

TREATMENT GUIDELINES

If we accept that this patient has severe pneumonia and consult the ATS guidelines for treating pneumonia (see box below), then the next step is to decide whether she has risk factors for Pseudomonas aeruginosa. She does not have bronchiectasis and has not received corticosteroids or antibiotics within the previous three months. However, she looks malnourished so treatment is begun with imipenem and ciprofloxacin.

The next day, blood cultures are reported to be growing Streptococcus pneumoniae, and a day later the antibiotic susceptibilities are provided by the laboratory. The minimal inhibitory concentration (MIC) of penicillin is 2 mcg/ml. Thus, this patient has pneumonia due to a penicillin-nonsusceptible isolate of S. pneumoniae. Isolates with an MIC of 0.06 mcg/ml or lower are susceptible; those with an MIC of 0.12 to 1 mcg/ml are of intermediate susceptibility; and those with an MIC of 2 mcg/ml or higher are resistant. Recently, penicillin resistance has been redefined so that for infections that do not involve the central nervous system (CNS), an MIC of 4 mcg/ml or higher is considered resistant. So our patient has a nonsusceptible isolate.

Imipenem is active against penicillin-resistant S. pneumoniae, but ciprofloxacin is not. Therefore, treatment with imipenem continues and the ciprofloxacin is stopped. There are some data from an observational study suggesting that the mortality rate from bacteremic pneumococcal pneumonia is lower when two antibiotics that are effective against S. pneumoniae are used. However, by now our patient has markedly improved so treatment is continued with imipenem only.
 

EPIDEMIOLOGY OF PENICILLIN-RESISTANT S. PNEUMONIAE

About 20% of the isolates of S. pneumoniae in Canada are penicillin resistant; in the United States, the figure is 24%. There is geographic variation in the rate of pneumococcal resistance. In Georgia, for example, about 33% of the isolates are penicillin resistant. Risk factors for penicillin-resistant S. pneumoniae are age under 5 or over 65, beta-lactam therapy within the past three months, alcoholism, immunosuppressive therapy (including corticosteroid therapy), multiple illnesses, and exposure to a child in a day care center.

Isolates that are resistant to penicillin are often resistant to other antibiotics. In the United States, resistance to three or more classes of antibiotics increased from 9% to 14% between 1995 and 1998. Currently, about 30% of S. pneumoniae isolates are resistant to macrolides, 30% to trimethoprim-sulfamethoxazole, 16% to tetracycline, 8% to clindamycin, and 1% to fluoroquinolones.

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia, accounting for about 50% of pneumonia cases requiring admission to a hospital. It also accounts for a significant proportion of cases of community-acquired pneumonia that do not require hospitalization. Thus, the risk of drug-resistant S. pneumoniae (DRSP) must be evaluated in every patient with pneumonia. For patients who are going to be treated on an ambulatory basis and in whom there is a risk of DRSP, the antibiotics listed in the box on page 27 are all acceptable choices.

Amoxicillin, amoxicillin-clavulinic acid, ceftriaxone, and cefditoren all have the same MIC as penicillin for any given isolate. For cefpodoxime, cefuroxime, and cefdinir, the MICs are two times higher; for cefprozil, four times higher; for cefixime and ceftibuten, 16 times higher; and for cefaclor, 32 times higher. This suggests that some beta-lactam antibiotics should not be used to treat patients with DRSP. It is true that many beta-lactams in high doses are effective against DRSP because of the high concentrations of these drugs that can be achieved in the lung. However, if there is concomitant meningitis, vancomycin and ceftriaxone should be used because with higher MICs, therapeutic concentrations of the beta-lactam may not be achieved in the CNS. In general, the drug concentration in the CNS required to treat an infection is ten times the MIC.
 

MECHANISMS OF RESISTANCE

There are two mechanisms of resistance to macrolides in S. pneumoniae. One is due to an efflux pump that moves the macrolide out of the bacterial cell; the other is due to an alteration of the target site. The first mechanism is a relative resistance, and since macrolides concentrate in alveolar macrophages, the significance of this type of resistance is unclear. However, alteration of the target site results in absolute resistance, with MICs of 64 mcg/ml or higher. In North America, the efflux type of resistance is more common than the target-site type.

Resistance to the fluoroquinolones is beginning to emerge. The major risk factor for fluoroquinolone resistance is prior treatment with ciprofloxacin, especially in patients with chronic obstructive lung disease, who often receive multiple courses of the drug. Patients who have received a fluoroquinolone in the past three months should not be given an antibiotic in this class as empiric therapy. Ciprofloxacin and levofloxacin are about equal in activity against S. pneumoniae, gatifloxacin is three times more active, and moxifloxacin is 10 times more active when the MIC and area under the concentration curve are considered. However, if an isolate of S. pneumoniae is resistant to one of the fluoroquinolones, it may be resistant to all of them.

It is noteworthy that the BTS guidelines for the treatment of community-acquired pneumonia on an ambulatory basis recommend amoxicillin alone as the drug of choice. North American guidelines emphasize coverage of atypical agents such as M. pneumoniae and hence have recommended macrolides or doxycycline as first-line agents for ambulatory pneumonia. It is very possible that the advent of DRSP in North America will mean a return to monotherapy with a beta-lactam for this condition. This is based on the observation that with the exception of pneumonia due to the Legionella species, atypical pneumonias are mild, affect younger individuals, and may not be susceptible to the influence of specific antibiotics on the course of the illness.

back to top

Printable version of this article

E-mail this article