Bacterial Infections of the Lung: Bacterial Pathogens and Therapy

feverCommon symptoms and signs of bacterial pneumonia are fever, chills or rigors, cough, purulent sputum production, pleurisy, dyspnea, and anorexia. In the case of anaerobic lung abscess or necrotizing pneumonia, symptoms are often present for several weeks before the patient seeks medical care.

Patients with pneumonia may occasionally fail to respond to that which is considered to be effective therapy; possible causes of such failure are shown in Table 2. Complications of bacterial pneumonia include necrosis of pulmonary parenchyma (necrotizing pneumonia or lung abscess), empyema, bacteremia, metastatic suppuration, pericarditis, and acute and chronic respiratory insufficiency.

Streptococcus pneumoniae: S pneumoniae is by far the most frequent bacterial cause of pneumonia; onset is classically an abrupt shaking chill or rigor, fever, dyspnea, pleuritic pain, and cough productive of rusty sputum. Lobar infiltration is common in adults. Bacteremia occurs in approximately 30 percent of patients with pneumococcal pneumonia and is associated with both metastatic infection and an appreciable increase in mortality.

Aqueous penicillin G (0.6 to 1.2 million units daily) is the agent of choice for uncomplicated pneumococcal pneumonia. S pneumoniae resistant to both penicillin and to many other commonly used antimicrobials have been recovered recently in several countries. Although resistant strains are rare in the United States, susceptibility testing should be performed whenever a suboptimal response to therapy occurs. A safe and effective polyvalent pneumococcal vaccine is now available.

Streptococcus pyogenes: S pyogenes (Group A p-hemolytic Streptococcus) is an occasional cause of epidemic and sporadic pneumonia.» Chills tend to be multiple, bronchopneumonia rather than lobar consolidation is typical, and both pleural effusion and empyema are frequent; treatment consists of 2 million units of aqueous penicillin G daily for two weeks or longer.

Streptococcus agalactiae: S agalactiae (group В 0-hemolytic Streptococcus) has recently been recognized to cause a variety of infections in adults, including pneumonia with or without bacteremia. Penicillin and ampicillin are active against S agalactiae; uncomplicated pneumonia should be treated with 4 to 6 million units of penicillin per day. Erythromycin should be an adequate substitute for any of the streptococcal pneumonias in the penicillin-allergic patient.

Staphylococcus aureus: S aureus is a relatively common cause of pneumonia and is most often associated with prior pneumonia due to influenza A virus, antecedent staphylococcal bacteremia, endocarditis, or hospitalization. Pulmonary infiltrates are patchy; pleural effusion, empyema, and lung abscess are relatively frequent.

A number of agents are active against S aureus. Those most commonly used for treatment of staphylococcal infections are the penicillinase-resistant penicillins (methicillin, nafcillin, or oxacillin) and the cephalosporins. Because the cephalosporins are relatively frequently associated with Clostridium difficile(pseudomembranous) colitis and other su-prainfections, the penicillinase-resistant penicillins are generally preferred therapy for staphylococcal infections. Pneumonia due to “methicillin-resistant” S aureus should be treated with vancomycin because both the penicillins and cephalosporins are usually ineffective. Tube thoracostomy or open surgical drainage of staphylococcal empyemas is almost always needed because of the viscous nature of the empyema fluid and the tendency for loculations to develop rapidly.Streptococcus

Group Y Neisseria meningitidis: N meningitidis was largely ignored as a primary pulmonary pathogen until the mid-1970s. Pneumonia due to meningococcal serogroups other than Y is usually secondary to meningococcemia and has a grave prognosis. In contrast, group Y meningococcal pneumonia is frequently not associated with either meningococcemia or meningitis.’ Patchy alveolar infiltration is the most common radiologic pattern and pleural effusion occurs in approximately 20 percent of patients. Penicillin G (1.2 million units daily) was highly effective in one large series. It should be recognized, however, that group Y N meningitidis also produces meningitis and fulminant meningococcemia; in such instances the dose of penicillin should be 8 to 24 million units daily.

BranhameUa (Neisseria) catarrhalis. B. catarrhalis has been considered to be a harmless commensal of the oral cavity. Although data are extremely limited, this organism is an unquestioned respiratory tract pathogen (Ref 19 and Dr. M.H. Louie et al, unpublished data). Some strains of В catarrhalis produce beta lactamase and may, therefore, be resistant to the penicillins; in such instances therapy with erythromycin, tetracycline, or a cephalosporin may be required to effect cure.

Haemophilus influenzae: Recent reports have emphasized the importance of H influenzae as an adult pulmonary pathogen. Common predisposing factors include chronic obstructive pulmonary disease (both H influenzae and S pneumoniae may colonize the airways of such individuals), ethanol abuse, and antecedent upper respiratory tract infection. Because H influenzae is a small gram-negative coccobacillus, it may easily be overlooked on gram stained smears of respiratory secretions.

Ampicillin (4 to 6 g daily) is the agent of choice for ^-lactamase-negative strains of H influenzae. Cefamandole has been recommended as an appropriate agent for p lactamase-producing strains; several recent reports, however, have documented therapeutic failure with cefamandole. Chloramphenicol is almost invariably active against H influenzae and is the agent of choice for ampicillin-resistant strains or for the patient with ampicillin allergy.

Legionella pneumophila: In the past five years a new and clinically quite significant pulmonary pathogen, Legionella, has been studied intensively. Although several different species of Legionella have been reported to cause pneumonia, most cases have involved L pneumophila.21 Legionellosis may be sporadic or occur in localized outbreaks in institutions such as hotels and hospitals. There are some clinical similarities between legionellosis and Mycoplasma pneumoniae infection. The illness may be gradual in onset; malaise, headache, anorexia, arthralgia, myalgia, and cough are common initial symptoms; recurrent shaking chills, watery diarrhea, nausea, and vomiting are relatively frequent. Cough is initially dry but may become productive of modest amounts of nonpurulent sputum. Fever is often nonremitting and frequently exceeds 39 to 40°C; relative bradycardia is often noted. Central nervous system manifestations are varied and include both cerebral and cerebellar dysfunction. Liver function abnormalities, and, occasionally, jaundice have been reported. Proteinuria, hematuria, and occasionally severe renal failure have been reported.

Gram stain of pulmonary secretions usually reveals scant polymorphonuclear leukocytes and no bacteria (the organism, a gram-negative bacillus, stains quite poorly in clinical specimens with gram’s reagents). The chest roentgenogram initially reveals patchy alveolar infiltration; subsequent spread of infiltration to the ipsilateral or contralateral lung is frequent. Consolidation is also frequent, and pleural effusion is present in most patients, whereas cavitation is uncommon.

Etiologic diagnosis can be made either by culture or by demonstration of the organism in pulmonary secretions or pleural fluid by immunofluorescence. Diagnosis by culture is somewhat limited by the lack of a highly selective medium for culture of sputum and by slow growth of the organism. Limitations of immunofluorescence include occasional cross-reactivity with other pulmonary pathogens and the need for multiple antisera directed against the various serogroups and species of Legionella. Serology is not of diagnostic value in the acute phase of illness. Diagnosis must often be made and therapy instituted on the basis of a suggestive clinical presentation.

AmpicillinErythromycin is currently the agent of choice for treatment of Legionella infections. Initially it should be given intravenously (4 g daily) in the seriously ill patient, and therapy should last for at least three weeks to avoid relapse. Tetracycline plus rifampin appears to be an acceptable alternative combination when erythromycin is contraindicated. Beta-lactam antimicrobials, chloramphenicol, clindamycin, and aminoglycosides are ineffective.

Aerobic and facultative gram-negative ЬасШ: Hospital-acquired pneumonias often involve gram-negative bacilli; they usually develop in association with immunosuppressive therapy, aspiration, mechanical ventilation, or as a consequence of bacteremia; and often have a high mortality rate. The most commonly reported pathogens have been mentioned above.

A great deal of confusion exists in the literature regarding the pathogenesis of gram-negative bacil-lary pneumonia. Without doubt, it may occur as a sequela of either bacteremia or accidental nebuliza-tion of bacteria into the airways. Many reports of gram-negative bacillary pneumonia, however, are attributed to oropharyngeal aspiration and yet have been diagnosed only by sputum culture. When the clinical setting is consistent with aspiration, the possibility of mixed anaerobic and facultative or aerobic infection should always be considered. Lorber and Swenson recovered anaerobes (usually in association with facultative or aerobic organisms) from eight of 23 cases of hospital-acquired aspiration pneumonia. Bartlett and Finegold reported 143 cases of anaerobic pleuropulmonary infections (35 percent of which were hospital-acquired) and were able to recover facultative or aerobic bacteria from 64 percent of pneumonias, 29 percent of necrotizing pneumonias, 42 percent of lung abscesses, and 40 percent of empyemas. Nonanaerobes recovered were S aureus, various Streptococcus species, and several species of pathogenic facultative or aerobic gram-negative bacilli. Moreover, they noted that 58 of 102 cultures of expectorated sputum yielded potential pathogens that were not detected by other techniques, such as transtracheal aspiration.

These data indicate that anaerobic pulmonary infections frequently involve gram-negative bacilli, that gram-negative bacillary pneumonia often involves anaerobes, and that sputum culture is not adequate for evaluation of such cases.

We believe that transtracheal aspiration (or other techniques that bypass the oral cavity) should be performed, whenever possible, in cases of complicated pneumonia. Gram stain and culture (aerobic and anaerobic) of pulmonary secretions obtained by transtracheal aspiration would provide important data both for initiation and subsequent modification of therapy. If transtracheal aspiration is not feasible, then sputum should be gram-stained, screened as outlined earlier, and cultured aerobically; empiric coverage for anaerobes should be added to the coverage given for facultative and aerobic organisms.

An aminoglycoside is usually given for treatment of gram-negative bacillary pneumonia; in addition, a broad-spectrum penicillin, such as carbenicillin or ticarcillin, is often added for dual coverage of P aeruginosa and, occasionally, for other gram-negative bacilli. The newer cephalosporins, such as cefoxitin and cefotaxime (and others that are currently under investigation), are often active against gram-negative bacilli, but should not be relied on (as a single agent) until susceptibility has been established in the laboratory. Therapy for anaerobes that may be involved in hospital-acquired (aspiration) pneumonia is outlined below.

Anaerobic pulmonary infection: This type of infection is almost invariably polymicrobial and usually involves several species of anaerobic bacteria, often in association with one or more facultative organisms. Three distinct types of anaerobic pulmonary infections (pneumonia, necrotizing pneumonia and lung abscess) have been described; all may be accompanied by empyema. The most important clinical clues, in addition to the presence of necrotizing pneumonia or abscess on chest roentgenogram, are conditions that predispose to impaired consciousness, periodontal disease, lower cranial nerve dysfunction, mechanical obstruction of an airway, and foul-smelling sputum Unfortunately, foul sputum is present in only about one half of cases.

Anaerobes most frequently isolated from pleuro-pulmonary infections are usually penicillin-susceptible and include members of the Bacteroides melaninogenicus-Bacteroides asaccharolyticus group, Fusobacterium nucleatum, Peptococcus species, and Peptostreptococcus species. Anaerobes that are more resistant to antimicrobials, such as Bacteroides fra-gilis and other species of Bacteroides, may be encountered in ~15 percent of cases. The most frequently encountered facultative or aerobic bacteria in mixed infections are S aureus, S pneumoniae, H influenzae, and facultative or aerobic gram-negative bacilli; one or more of these organisms is present in one-third to one half of anaerobic pleuro-pulmonary infections.» Empyema involving anaerobes invariably requires drainage by either tube thoracostomy or an open surgical procedure.

Penicillin is usually effective for treatment of anaerobic pleuropulmonary infection and is initially given in a daily dose of 6 to 10 million units or more. Once signs and symptoms of toxicity have abated, therapy may be given by the oral route. Anaerobic pneumonia responds rather promptly to therapy, whereas lung abscess and necrotizing pneumonia may require six to ten weeks or longer of therapy to effect a cure. Carbenicillin, ticarcillin, and cefoxitin are also active against most clinically significant anaerobes except 5 to 10 percent of the В fragilis group; these antimicrobials do not appear to possess any advantage over penicillin G in most cases of anaerobic pulmonary infection, however. Clindamycin is an effective substitute in the patient with penicillin allergy. In the patient with life-threatening infection, it may be prudent to administer an agent such as clindamycin or metronidazole (both preferably supplemented with penicillin G), or chloramphenicol in order to provide coverage for В fragilis and other resistant anaerobes.

Miscellaneous Causes of Bacterial Pneumonia

Several additional species of bacteria are rare causes of primary pneumonia. These include Bacillus anthrads, FrancisceUa tularensis, Pseudomonas pseudomallei, and Yersinia pestis.

Nocardia asteroides causes pneumonia, often cavitary, particularly in patients who are diabetic, alcoholic, or immunosuppressed. Nocardia infections tend to extend to the pleura and chest wall and to metastasize to the brain. A sulfonamide, such as sulfadiazine, is the agent of choice for pulmonary nocardiosis and should be given for a minimum of six weeks to avoid relapse. Minocycline, erythromycin, ampicillin, trimethoprim, and possibly amikacin and cycloserine may also be useful in combination with a sulfonamide. Empyema and metastatic foci require surgical drainage.

Summary

Bacterial infection of the lung is an important cause of morbidity and mortality in adults and usually develops as a consequence of aspiration of bacteria that colonize the oropharynx. The etiologic agent of pneumonia may be diagnosed incorrectly, particularly when a “routine” sputum culture is relied on for diagnosis.

Recent studies have demonstrated that S agalactiae, В catarrhalis, Group Y N meningitidis, H influenzae, and Legionella sp are important pulmonary pathogens in adults.

Table 2—Reasons for Failure or Apparent Failure of Pneumonia to Respond to Antimicrobial Therapy

Pulmonary infiltrate not of infectious etiology
Pulmonary infection of nonbacterial etiology
Bronchial obstruction or foreign body
Empyema not adequately drained
Bacterial pathogen resistant to agent administered
Suprainfection with resistant organismInadequate dosage or duration of antimicrobial therapy
Drug fever
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