Pulmonary Tuberculosis

Pulmonary tuberculosis is estimated to account for 2 million deaths annually world wide and ranks second only to HIV disease as an infectious cause of death. In 1999 there were about 8.4 million new cases and it is believed that 1.7 billion people or nearly one third of the world’s population are infected.

The transmission of tuberculosis is by way of the air borne droplet nuclei. Particles generated from an active infectious source (such as a patient with cavitory lung disease) by sneezing or coughing, rapidly lose its water content on contact with the ambient air. These droplet nuclei of 1-5 micron in size will reach the alveoli of the lungs when breathed. Initial infection with the tubercli bacilli is characterized by lymphohematogenous spread with widespread dissemination of the organism throughout the body. In about 5-10% of infected person, the disease directly progresses from this primary infection. In the majority remainder, the disease becomes latent only to reactivate at a later date. In normal host the life time risks of developing reactivation tuberculosis is estimated to be about 10% with about half the cases occurring in the first 2-3 years after infection. Reactivation characteristically occur in the upper lobes of the lungs but could be extrapulmonary.

In the United States where the burden of the diseases is comparatively low, the main efforts are to detect latent disease as well as active cases. CDC recommends the persons at increased risk sould be tested, examples are persons with close contact with persons known to have active tuberculosis, health care workers at facilities where TB are treated, and HIV-infected persons.

Basic principles for the treatment of tuberculosis are 1) Multiple chemo-therapy, 2) Regimen must include at least 2 drugs to which the organism is susceptible, 3) Drugs must be taken regularly, preferably under direct supervision, 4)Duration of treatment must be sufficient, normally no less than 6 months and 4) Never add a single drug to a failing regimen, to avoid drug resistance.

Recommended regimens for latent tuberculosis infection are isoniazid for 6-9 months (adults, 5 mg/kg (max. 300 mg) daily or 900 mg twice weekly, children, 10-20 mg/kg (max 300 mg); rifampin for 4 months (adults, 10 mg/kg (max. 600 mg), children, 10-20 mg/kg (max. 600 mg); or rifampan and pyrazinamide for 2 months ( adults, 5 mg/kg of rifampin, max 300 mg and 15-20 mg of pyrazinamide/kg, max. 2000 mg. Not recommended for pregnant children or children.)

There are 3 treatment options for smear- and culture- positive cases:

Option 1. Initial phase, daily isoniazid, rifampin and pyrazinamide for 8 weeks. Continuation phase, isoniazid and rifampin daily or 2 or 3 times per week for 16 weeks.

Option 2. Initial phase, daily isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin for 2 weeks followed by 6 weeks of the same drugs given twice weekly, through direct observed therapy. Continuation phase, isoniazid and rifampin 2 times per week for 16 weeks, through direct observation therapy.

Option 3. Isoniazid, rifampin, pyrazinamide, and ethambutoal or strep-tomycin 3 times per week for 6 months through direct observation therapy.

Community Acquired Pneumonia

In the United States pneumonia is the sixth leading cause of death and the first leading cause from infectious diseases. Community acquired pneumonia accounts for 5.6 million cases annually and 1.1 million hospital admissions. Mortality various from 1-5% to 12% in hospital patients and as high as 40% in intensive care units.

The types of causative organisms are more associated with the type of patient and the severity of the illness. The most common organism remains the Streptococcus pneumoniae. Other etiological agents include H. Influenzae, Enteric gram negatives, the atypicals (Legionella, M. Pneumoniae, C. Pneumoniae and M. Catarrhalis), Staph aureus and pseudomonas in adition to viruses and mixed anaerobic organism from aspiration.

Modifying factors that increase the risk of infection with specific pathogens are: (1) For penicillin-resistant and drug-resistant pneumococci – age >65, β-Lactam therapy within the past 3 months, alcoholism, inmmune-suppressive illness, multiple medical comorbidities, and exposure to a child in a day care center. (2) For enteric gram-negatives – residence in a nursing home, underlying cardiopulmonary disease, multiple medical comobidities and recent antibiotic therapy. (3) For pseudomonas aeruginosa – structural lung disease (bronchiectasis), corticosteroid therapy (>10 mg of prednisone per day), broad-spectrum antibiotic therapy for 7 days in the past month and malnutrition.

Importantly, an etiologic agent in not identifiable in about 50% of cases. The principle of treatment should therefore, be empiric, based on the likely pathogen. Treatment started within 8 hrs significantly reduce morbidity and mortality.

For outpatients with little risk of drug resistant pneumococcal pneumonia, a new macrolide is recommended. Patients with likelihood of drug resistant pneumococci can be treated with a combination of a newer β-lactum (Cefuroxime, Ceftriaxone, Unasyn, Augmentin) and a macrolide or a newer quinolone (Levofloxacin, Gratifloxacin). Patients with possible pseudomonal infection need to be treated with two antipseudemonal antibiotics (Imipesam, Zosyn, Cefepime, Ciprofloxacin, aminoglycoside) as well as coverage for atypical organisms.

Finally, pneumococcal and influenza vaccination should be considered as additional measures for prevention of pneumonia in susceptible individuals.

(Dr. King is Associate Professor of Medicine, Weill Medical College of Cornell University.)