SPECIFIC PATHOGENIC ORGANISMS



Viral Agents. Viral infection is usually limited to the upper respiratory tract, and only a small proportion of infected patients develop pneu­monia. In children, viruses are the commonest cause of pneumonia, and respiratory syncytial virus is the most frequent organism. In adults, vi­ruses are estimated to account for less than 10 per cent of pneumonias, and influenza is the com­monest organism. Patients at increased risk of in­fluenzal pneumonia include the aged, patients with chronic disease of the heart, lung, or kidney, and women in the last trimester of pregnancy. Cy­tomegalovirus has developed prominence as a cause of pneumonia in immunosuppressed pa­tients, particularly in AIDS and the post-trans­plantation state, in which it has a mortality rate of about 50 per cent. When varicella occurs in adults some 10 to 20 per cent develop pneumonia, which commonly leaves a pattern of diffuse punc­tate calcification on chest x-ray. Measles is oc­casionally complicated by a typical viral pneu­monia. Viral pneumonias typically occur in community epidemics and usually develop 1 to 2 days after the onset of “flu-like” symptoms. Major features include a dry cough, dyspnea, gen­eralized discomfort, unremarkable physical ex­amination, and an interstitial pattern on chest x-ray. A presumptive diagnosis may be made on the basis of the clinical presentation and the epide­miologic setting. Viral isolation or serology is re­quired for confirmation but is rarely of clinical value.

Staphylococcus aureus. This accounts tor 2 to 5 per cent of community-acquired pneumonia, 11 per cent of hospital-acquired pneumonia, and 26 per cent of pneumonia following a viral infection. Persistent nasal colonization is observed in 15 to 30 per cent of adults, and 90 per cent display in­termittent colonization. Presentation is similar to that of pneumococcal pneumonia, but contrasting features include the development of parenchymal necrosis and abscess formation in up to 25 per cent, empyema in 10 per cent, and a hematoge­nous source of infection, particularly septic thrombophlebitis, infective endocarditis, or an in­fected intravascular device. If the pneumonia is hematogenous in origin, blood cultures are usu­ally positive and associated skin lesions occur in 40 per cent. Sputum Gram’s stain may reveal grapelike clusters of gram-positive cocci. S. au­reus is recovered very easily from mixed culture samples so that its absence in a purulent specimen usually excludes it as a cause of the pneumonia. Treatment requires a penicillinase-resistant agent such as nafcillin.

Streptococcus pyogenes. This is now a rare cause of pneumonia, probably accounting for less than 1 per cent of all cases. Carriage rate in the pharynx, about 3 per cent in adults, is less than with the other gram-positive cocci. Presentation is similar to that observed with S. pneumoniae and S. aureus, except that empyema is found in 30 to 40 per cent of cases. Gram’s stain reveals gram-positive cocci in pairs or chains. Penicillin G is the treatment of choice.

Gram-negative Bacilli. GNB have emerged as pathogens of major importance with the intro­duction of potent antibiotics and the proliferation of ICU’s. They are frequently encountered in pa­tients with debilitating diseases such as chronic alcoholism, cystic fibrosis, neutropenia, diabetes mellitus, malignancy, and chronic diseases of the lungs, heart, or kidney. They are ubiquitous throughout the hospital, contaminating equip­ment and instruments, and are the major source of nosocomial pneumonia. Specific organisms are associated with certain situations; e.g., Klebsiella pneumonia is particularly common in chronic al­coholics, Escherichia coli pneumonia is associ­ated with bacteremias arising from the intestinal or urinary tracts, and Pseudomonas aeruginosa is almost universal in cystic fibrosis. Precise etio­logical diagnosis is confounded by the frequency with which these organisms colonize the upper airways in predisposed patients. Treatment in this situation generally includes the use of a penicil­linase-resistant penicillin or a cephalosporin and an aminoglycoside. Haemophilus influenzae is a gram-negative coccobacillus almost universally present in the upper respiratory tract; thus its identification in sputum samples carries no significance. Diagnosis depends on isolating the or­ganism in the blood, pleural fluid, or lung tissue. Pneumonia is complicated by a high incidence of pleural reactions. Ampicillin is the treatment of choice, but 20 per cent show resistance due to beta-lactamase production.

Mycoplasma pneumoniae. This is not only a common cause of pneumonia in young adults, but it also produces a wide range of extrapulmonary features that may be the only findings. Less than 10 per cent of infected patients develop symptoms of lower respiratory tract infection. Respiratory findings resemble those of viral pneumonia. Non-pulmonary features include myalgias, arthralgias, skin lesions (rashes, erythema nodosum and mul­tiforme, Stevens-Johnson syndrome) and neuro­logical complications (meningitis, encephalitis, transverse myelitis, neuropathy). Definitive di­agnosis is delayed by technological limitations. Isolation and serology take several weeks for pos­itive results. Cold agglutinins are-found in 50 per cent of patients but take 7 to 14 days of infection before becoming positive, and they are also ele­vated in other respiratory infections. Tetracycline and erythromycin decrease the duration of symp­toms and hasten radiographic resolution but do not eradicate the organism from the respiratory tract.

Pneumocystis carinii. This protozoan parasite exists as a cyst, 5 u.m in diameter, containing oval bodies or sporozoites. Severe clinical infectio’n is probably secondary to reactivation of latent in­fection due to immunosuppression, particularly affecting cell-mediated immunity. Corticosteroids seem to be more important than cytotoxic therapy in predisposing to infection. Currently, this is the major pulmonary infection in patients with AIDS. Patients usually present with dyspnea, dry cough, and diffuse patchy infiltrates. Diagnosis requires bronchoscopy, with bronchoalveolar lavage and transbronchial biopsy, or open-lung biopsy. Go-mori methenamine silver nitrate usually stains the cyst wall black or brown. Definitive etiological diagnosis rather than employment of empirical therapy is desirable, as P. carinii accounts for no more than one third of diffuse pulmonary infil­trates in immunocompromised patients. Treat­ment of choice is trimethoprim-sulfamethoxa­zole, or pentamidine if the patient is allergic to the former agent.

Legionella species. These are fastidious GNB that were responsible for respiratory infections long before the outbreak of Legionnaires’ disease in 1976. They are distributed widely in water, and outbreaks have been related to their presence in cooling towers, condensers, potable water, and even hospital shower heads. Infection may occur sporadically or in outbreaks. While healthy sub­jects are affected, there is an increased risk in pa­tients with chronic diseases of the heart, lungs, or kidneys, malignancy, and impairment of cell-me­diated immunity. After an incubation period of two to ten days the illness usually gradually be­gins with a dry cough, respiratory distress, fever, rigors, malaise, weakness, headache, confusion,and gastrointestinal disturbance. The chest x-ray shows alveolar shadowing that may have a lobar or patchy distribution, with or without pleural ef­fusions. The diagnosis is clinically suggested by the combination of a nonconsolidating pneu­monia, dry cough, multiorgan involvement, and failure to respond to antibiotics other than eryth­romycin (although the latter should not be nec­essary to arouse suspicion).

Diagnosis can be made by four methods. (1) In­direct fluorescent antibody testing is positive in 75 per cent of patients, but up to eight weeks is required for seroconversion. (2) Direct fluorescent antibody of respiratory secretions is the most rapid method of establishing the diagnosis and has a specificity of 95 per cent. (3) Fresh fluids and tissues should be subjected to the Gimenez stain, which is more sensitive and specific than the previously employed Dieterle silver stain. (4) The organism can be cultured on charcoal yeast extract medium, but up to ten days is required for growth.
Erythromycin is the treatment of choice and ap­pears to result in a four-fold reduction in mortal­ity. Patients usually respond within 12 to 48 hours, and it is very unusual for fever, leukocy­tosis, and confusion to persist after four days of therapy. In the untreated situation, the recorded mortality rate is 20 to 30 per cent in a previously healthy host and 80 per cent in immunocom­promised patients.

Tuberculosis. Mycobacterium tuberculosis is transmitted in aerosolized droplets, and the ma­jority of infected patients develop an asympto­matic, self-limited pneumonia that heals by gran­uloma formation with eventual scarring and calcification. Sensitization develops two to ten weeks after infection, evidence of which can be obtained by demonstrating reactivity on skin test­ing with an extract of the tuberculous bacillus (purified protein derivative, PPD). Less than 15 per cent of infected patients ever develop active disease. The onset of symptoms may follow di­rectly after infection or may occur many years later owing to the breakdown of a previously healed focus of disease. The risk of progressing to disease is increased in certain situations such as immunocompromise, diabetes mellitus, malnu­trition, silicosis, and maintenance hemodialysis. Active disease may involve any organ system. In the lung it may proliferate locally, producing ca­seation and necrosis, or it may rupture into a bron­chus and result in pneumonia. On the chest x-ray the apical and posterior segments of the upper lobes are most commonly involved, and the ap­pearance may be that of a single nodule, segmen­tal infiltrate, or diffuse acinar shadow, with or without calcification and cavitation. Other sites include the pleural space, genitourinary tract, bone, pericardium, meninges, and peritoneum. Invasion of a blood vessel with hematogenous spread may result in miliary tuberculosis, so termed because of the appearance of millet-seed type shadows on the chest x-ray. With a charac­teristic x-ray, diagnosis is easy, but the features of miliary tuberculosis may be subtle and it may present as a fever of unknown origin without ob­vious pulmonary involvement.

Isolation of the organism is required for diag­nosis. Ziehl-Neelsen stain of the sputum demon­strates the acid-fast organisms but must be differ­entiated from atypical mycobacteria or nocardia. Fluorescent microscopy is more sensitive but less specific. Culture takes three to eight weeks before yielding positive results. Single morning sputum samples are the preferred source of material. If no sputum can be obtained, gastric aspirates or bron­chial washings should be obtained. A negative sputum smear in the presence of cavitary disease places the diagnosis in doubt. Most patients with active disease demonstrate sensitivity on skin testing when 0.1 ml of standard PPD (intermediate strength) is injected intradermally. Induration of at least 10 mm in diameter is deemed significant, but this varies with the prevalence in the com­munity. Interpretation is complicated by the fact that some patients with active disease are anergic.

Currently the recommended treatment is ison-iazid (300 mg/day) and rifampin (600 mg/day) for nine months, which results in treatment failures and relapses in only 1 per cent of patients. The addition of a third agent (such as ethambutol or streptomycin) does not improve the rate of spu­tum conversion but may increase toxicity.

Mycobacteria other than M. tuberculosis are fre­quent causes of chronic pulmonary infection, par­ticularly in patients with chronic lung diseases such as COPD and silicosis. Fifteen per cent of mycobacterial infections are estimated to be due to such agents. The most common organisms are M. kansasii and M. avium-intracellulare. Disease is usually confined to the lung and while possible, extrapulmonary involvement is rare. The excep­tion to this is in patients with AIDS, in whom disseminated M. avium-intracellulare is becom­ing an increasingly common problem. This or­ganism displays marked antibiotic resistance.

Fungi. Although an uncommon cause of pneu­monia, the lungs are frequently involved in sys­temic fungal infections. The responsible organisms can be divided into two groups; those associated with impaired host defenses (Asper­gillus, Mucor, and Candida) and those occurring in normal subjects [Histoplasma capsulatum, Coccidioides immitis, and Blastomyces dermati-tidis). Cryptococcus neoformans may infect both normal and immunocompromised hosts.