Antiobiotic treatment is dictated by the severity of the pneumonia, the clinical state of the patient, and the susceptibility patterns of the community.
Pneumonia (together with influenza) is the sixth leading cause of death in the United States, with an estimated 4 million cases annually. Patients who enter the intensive care unit suffer a 15% to 20% mortality rate.1 Community-acquired pneumonia (CAP) is an acute lower-respiratory–tract infection that develops in nonhospitalized individuals. It remains a common and serious illness, despite the availability of potent antibiotics.
In recent years, both the causes and the treatment of CAP have undergone changes. CAP is increasingly common among older people and those with coexisting illnesses. Such illnesses include chronic obstructive lung disease, diabetes, kidney failure, and congestive heart failure. Patients may become infected by a variety of newly identified or previously unrecognized pathogens. At the same time, bacterial resistance to antibiotics has been on the rise, making treatment difficult.
The pathogens that can cause CAP are listed in Table 1. The most common pathogens are Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Moraxella catarrhalis.
S. pneumoniae is the most common cause of CAP, accounting for up to 75% of cases.2 The identification of more than one pathogen in an individual with CAP is unusual, occurring in more than 10% of cases.3 Newly recognized etiologic agents include Chlamydia pneumoniae, Legionella species, and Hantavirus.4
Epidemiologic Factors Related to Specific Pathogens
A detailed history is important in the evaluation of CAP. Clues from the patient’s history can narrow diagnostic considerations, making it easier to select appropriate empiric antibiotic therapy. Several important associations are seen for CAP:
• in patients with alcoholism, CAP is commonly caused by oral anaerobes (Bacteroides species), gram-negative bacilli (Klebsiella species), and S. pneumoniae;
• in patients confined to nursing homes, CAP is commonly caused by S. pneumoniae, gram-negative bacilli, and H. influenzae;
• in patients with chronic obstructive lung disease and in heavy smokers, CAP is commonly caused by H. influenzae, S. pneumoniae, and M. catarrhalis;
• in patients who are exposed to birds, CAP is commonly caused by Chlamydia psittaci;
• in patients who are exposed to still water, as found in buildings with stagnant water in air-conditioning ducts, swimming pools, and spa whirlpools, CAP is commonly caused by Legionella species;
• in patients with poor dental hygiene, CAP is commonly caused by oral anaerobes (Bacteroides species);
• in patients with HIV infection, CAP is commonly caused by Pneumocystis carinii, S. pneumoniae, H. influenzae, and Mycobacterium tuberculosis; and
• in patients with influenza, CAP is commonly caused by viruses, S. pneumoniae, and Staphylococcus aureus.
There are many facets of treatment for CAP. These include initial assessment of the severity of the pneumonia, which dictates the site of treatment (home, hospital, or intensive care unit); appropriate supportive care (fluids, oxygenation); investigation and treatment of comorbid conditions (chronic obstructive lung disease or ischemic heart disease); end-of-life decision-making (do-not-resuscitate status and the initiation and termination of ventilator support); and discharge decisions.
One of the first steps in the management of patients with CAP is to decide whether they need to be hospitalized. Once pneumonia is suggested by chest-radiography findings, it is a challenge to determine which patients can be treated as outpatients and which should be hospitalized.
The usual indications for hospitalization include abnormal vital signs; altered mental status; hypoxemia; pneumonia-related infection (for example, empyema or endocarditis); severe abnormalities in blood-test results; acute medical conditions other than pneumonia that require immediate attention; and the presence of risk factors for a complicated course of pneumonia (age of more than 65 years, coexisting morbid illness, temperature of more than 38.3°C, immunosuppression, or culture-confirmed high-risk pneumonia, which is defined as that associated with airway obstruction or caused by S. aureus, gram-negative rods, or aspiration.
Recommendations for the empiric treatment of CAP are constantly changing. Very few data from randomized clinical trials of treatment of CAP are available to guide the selection of antimicrobial therapy. Recently, the Infectious Diseases Society of America4 (IDSA) published guidelines for the treatment of CAP. According to the IDSA guidelines (Table 2), antimicrobial recommendations are based on how the patient is categorized.
For empiric therapy, the IDSA recommends macrolides, doxycycline, and fluoroquinolones as suitable alternatives for primary therapy because each has activity against common pathogens, as well as many atypical organisms. In serious cases of pneumonia, the fluoroquinolones, erythromycin, or azithromycin should be supplemented by cefotaxime, ceftriaxone, or a b-lactam/b-lactamase inhibitor to provide extended gram-negative coverage.5
Inpatient empiric therapy for particularly severe CAP should consider Legionella species and other pathogenic bacteria as possible sources of infection. The therapeutic program should be modified further for patients with structural disease of the lung, penicillin allergy, or suspected aspiration pneumonia.
Recent studies have shown that patients can usually be switched from intravenous to oral therapy within 3 days, provided that a good oral antibiotic is available and that the patient is in clinically stable condition (and can tolerate the drug).6 Treatment for S. pneumoniae should generally continue for 10 to 21 days, or until the patient has been afebrile for 72 hours.5 Azithromycin is a good choice for treatment of atypical pathogens, but its utility against S. pneumoniae depends on community susceptibility.
The expected response to antibiotic therapy is an amelioration of symptoms over the first 72 hours. Some patients fail to respond to initial empiric therapy, or their conditions begin to deteriorate. When this happens, one must first question whether the initial diagnosis was correct. If the diagnosis was correct, then host, drug, or pathogen factors may be preventing a successful response.4 Host factors include obstruction, foreign bodies, inadequate immune response, and superinfection. Drug factors can include choosing the wrong drug (a drug to which the causative pathogen is resistant), errors in dosage or administration route, or an adverse drug reaction. Pathogen factors include incorrect identification of the pathogen, which may not be bacterial.
The Problem of Resistance
Antibiotic resistance has developed in several important CAP pathogens over the past 2 decades. The most important type of resistance that affects the choice of antibiotic is the production of b-lactamase. About 10% of S. pneumoniae strains1,2,5 are resistant to penicillin. Approximately 15% to 20% of H. influenzae strains1,3 are resistant to ampicillin, and about 85% of M. catarrhalis strains1,3,5 are resistant to both penicillin and ampicillin.
Several new strains of resistant bacteria—in particular, methicillin-resistant S. aureus (MRSA) and vancomycin-intermediate S. aureus (VISA)—are of particular concern because they may cause serious, difficult-to-treat infections in hospitalized patients with CAP.
MRSA was first described in 1961, shortly after the introduction of penicillinase-resistant b-lactam antibiotics into clinical practice. Since then, hospitals worldwide have reported varying proportions of MRSA among S. aureus isolates. Over time, several MRSA isolates have acquired resistance to other antibiotics; thus, MRSA has become a real clinical and therapeutic problem.
Today, MRSA is a major nosocomial pathogen found in an increasing number of hospitals worldwide. According to data from the National Nosocomial Infection Surveillance System,7,8 the percentage of MRSA among all S. aureus isolates rose from 2% in 1975 to 29% in 1991. This is a frightening fact that affects not only large teaching hospitals, but also small hospitals and nursing homes.9
S. aureus is one of the most common causes of both hospital-acquired and community-acquired infections worldwide, and the antimicrobial agent vancomycin has been used to treat many S. aureus infections (particularly those caused by MRSA). Although S. aureus remains susceptible to vancomycin, the emergence of strains with only intermediate susceptibility to the antibiotic is raising fears that the emergence of a fully resistant strain is to be expected.
Organisms are deemed susceptible to vancomycin if the minimum inhibitory concentration is 4 or fewer µg/mL, intermediately susceptible at 8 to 16 µg/mL, and resistant at 32 or more µg/mL. The first report of an infection with a strain of S. aureus that had only intermediate susceptibility to vancomycin came from Japan in June 1996.10 This report raised concern among infectious disease experts and led the Centers for Disease Control and Prevention (CDC) to issue interim recommendations for the control of VISA infections.11 More recently, there were two reports of VISA infections in the United States.12,13
The mechanism through which staphylococci become resistant to vancomycin is not clearly understood. Investigators have isolated a vancomycin-resistant S. aureus mutant in vitro that appeared to have structural cell-wall alterations that increased its ability to bind vancomycin.14 The researchers theorized that this alteration might prevent vancomycin from reaching crucial sites of cell-wall synthesis, thus impeding its bactericidal effect.
Most cases of VISA infections have one feature in common: the organism was initially sensitive to the antibiotic, but a moderately resistant strain was subsequently isolated after prolonged vancomycin use.
The CDC recommends that all clinical isolates of S. aureus be tested for susceptibility to vancomycin. Laboratory personnel should notify the laboratory director if vancomycin-resistant or vancomycin-sensitive S. aureus is discovered. Many isolates of S. aureus presumed to have been vancomycin-resistant have been found to be mixed with other organisms in cultures; therefore, vancomycin resistance should be confirmed by restreaking the colony to certify that the culture is pure. The hospital epidemiology program should be notified so that it can institute appropriate isolation procedures. The public health department, other hospitals in the vicinity, and the CDC should also be notified.
CAP is a common and severe illness. S. pneumoniae is the most common cause of CAP; however, many microorganisms may cause this illness. Antibiotic treatment is dictated by the severity of the pneumonia, the clinical state of the patient, and the susceptibility patterns of the community. N
John D. Zoidis, MD, is a contributing writer for RT Magazine.
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