Tuberculosis

GENERAL PRINCIPLES

• Approximately 1.7 billion people are infected with TB; although 14 days, hemoptysis, dyspnea, fever, night sweats, weight loss, or fatigue. Misdiagnosis and treatment with a fluoroquinolone for presumed CAP can lead to treatment delay and fluoroquinolone resistance.

• Extrapulmonary disease can present as cervical lymphadenopathy, genitourinary disease, osteomyelitis, miliary dissemination, meningitis, peritonitis, or pericarditis.

Diagnostic Testing

• Chest radiography may reveal focal infiltrates, nodules, cavitary lesions, miliary disease, pleural effusions, or hilar/mediastinal lymphadenopathy. Reactivation disease classically involves the upper lobes.

• Three sputum specimens should be sent for AFB smears and cultures. A diagnosis of active TB is made with a positive AFB smear, a positive NAAT for M. tuberculosis complex, or positive culture. Nontuberculous mycobacteria (NTM) may be positive on smear but negative on NAAT. AFB smear sensitivity can be up to 90%, if three sputum samples are tested.

• All patients with confirmed or suspected TB should undergo HIV testing.

• M. tuberculosis can take several weeks to grow in culture, so if the clinical suspicion is high, presumptive therapy even with negative smears may be indicated until cultures are negative.

• Antimicrobial susceptibility testing should be performed on all initial isolates and on isolates obtained from patients who do not respond to standard therapy. Rapid detection of rifampin resistance, possible with molecular techniques (Cepheid Gene Xpert MTB/RIF), correlates with MDR-TB. Genetic testing on direct specimens is also available for select cases through the CDC (molecular detection of drug resistance).

• LTBI may be diagnosed by a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA). Current guidelines recommend IGRA testing in all individuals 5 years or older, rather than TST.²⁴ Available IGRAs include QuantiFERON-TB assay and T-SPOT.TB assay, both approved by the FDA.

TREATMENT

Active TB

• Hospitalized patients with active TB should be placed in airborne isolation in a negative-pressure room. Healthcare personnel should use an N95 or powered air purifying respiratory during patient care.

• The local health department should be notified of all TB cases so that contacts can be identified and directly observed therapy (DOT) administered when the patient is discharged. DOT is essential to ensure adherence and prevent emergence of drug resistance.

• Multidrug anti-TB treatment regimens are required because drug resistance develops when a single drug is administered. Extended therapy is necessary because of the prolonged generation time of mycobacteria.

• The intensive phase of therapy (first 8 weeks) for uncomplicated pulmonary TB should consist of four drugs (RIPE): rifampin (RIF, 10 mg/kg; maximum, 600 mg PO qday), isoniazid (INH 5 mg/kg; maximum, 300 mg PO qday), pyraz inamide (PZA, 15-25 mg/kg; maximum, 2 g PO qday), and ethambutol (EMB, 15-25 mg/kg PO qday). Pyridoxine (vitamin B₆) 25-50 mg PO qday should be used with INH to prevent sensory neuropathy. If the isolate proves to be fully susceptible to INH and RIF, then EMB can be dropped and INH, RIF, and PZA continued to complete this initial phase.

• The continuation phase consists of 16 weeks of INH and RIF to reach a standard total of 6 months of therapy for pulmonary TB. Patients at high risk for relapse (cavitary pulmonary disease or positive AFB cultures after 2 months of therapy) should be treated for an additional 28 weeks beyond the 8ญweek initial phase, for a total of 9 months.

• Daily therapy is the most efficacious regimen and it is recommended in patients with HIV. Thrice weekly therapy can be considered in the continuation phase.

• Therapy for pregnant women or multidrug-resistant TB often requires individualized drug regimens, and consultation with an expert in the treatment of TB is strongly recommended.

• Extrapulmonary disease in adults can be treated in the same manner as pulmonary disease, with 6ญmonth regimens, except for bone and joint infection (9-12 months) and central nervous system (CNS) TB (12 months).²⁵

• Glucocorticoids in combination with antituberculous drugs are only recommended in tuberculous meningitis but not routinely for tuberculous pericarditis. Prednisone 1 mg/kg (maximum, 60 mg) PO qday or dexamethasone 12 mg IV qday is tapered over several weeks.

Latent TB

• Chemoprophylaxis for LTBI should be administered only after active disease has been ruled out by clinical assessment and chest radiography.

• Risk factors for progression include a positive conversion within 2 years of a previously negative TST or IGRA; a history of untreated TB or radiographic evidence of previous fibrotic disease (calcified granulomas in the absence of fibrosis do not confer increased risk); patients with HIV infection, diabetes mellitus, end-stage renal disease, hematologic or lymphoreticular malignancy, chronic malnutrition, or silicosis or who are receiving immunosuppressive therapy; and close contacts (household members) of patients with active disease who have been diagnosed with LTBI.

• Persons with advanced HIV infection or other severely immunocompromised states (e.g., transplant) who have had known contact with a patient with active TB should be treated for LTBI.

• INH 300 mg PO qday for 6-9 months is the most studied regimen for LTBI who have risk factors for progression to active disease, regardless of age. However, and can be low risk (uncomplicated) or high risk (complicated).

• Infections are typically polymicrobial with enteric gram-negative bacilli (e.g., E. coli, Klebsiella spp.), Enterococcus spp., and especially anaerobes such as Bacteroides fragilis.

• Low-risk community-acquired infection includes acute diverticulitis, colitis, or appendiceal abscess.

• High-risk community infections occur in patients at risk for adverse outcomes or resistant pathogens (e.g., age >70 years, comorbidities, immunocompromised, delayed source control).

• Health care-associated infections (HAIs) may be caused by multidrug-resistant organisms (MDROs) and require additional antibiotics if ESBL-producing organisms or MRSA are a consideration.

TREATMENT

• Start empiric antibiotics promptly. See Table 14-10.

TABLE 14-10

EMPIRIC THERAPY EXAMPLES FOR INTRA-ABDOMINAL INFECTIONS²⁸

Oral Regimens

• Amoxicillin-Clavulanate 875 mg/125 mg PO q12h

• Ciprofloxacin 500-750 mg PO q12h + metronidazole 500 mg PO q8h

• Moxifloxacin 400 mg PO qday

Parenteral Regimens

Low risk—no concern for Pseudomonas aeruginosa

• Ertapenem 1 g IV q24h

• Ceftriaxone 1-2 g IV qday + metronidazole 500 mg IV q8h

• Piperacillin/tazobactam 4.5 g IV q6h

High risk—concern for P aeruginosa

• Piperacillin/tazobactam 4.5 g IV q6h

• Cefepime 1-2 g IV q8h + metronidazole 500 mg IV q8h

• Ciprofloxacin 400 mg IV q8-12h + metronidazole 500 mg IV q8h

• Meropenem 1 g IV q8h or imipenem-cilastatin 500 mg IV q6h

Concern for vancomycin-resistant Enterococcus spp.^a

• Add linezolid 600 mg PO/IV q12h or daptomycin 6-8 mg/kg IV qday to above regimens

Concern for yeast^a

• Add echinocandin (e.g., micafungin 100 mg IV qday) or fluconazole 400 mg PO/IV qday to above regimens

^aIf isolated from a sterile site.

• Source control with abscess drainage or surgical resection is critical.²⁸

• Avoid clindamycin, cefoxitin, and moxifloxacin due to increased resistance among B. fragilis.