Guidelines for Preventing the Transmission of Mycobacterium tuberculosis
in Health-Care Settings, 2005

Diagnostic Procedures

Diagnostic procedures should be performed in settings with appropriate infectioncontrol capabilities. The following recommendations should be applied for diagnosing TB disease and for evaluating patients for potential infectiousness.

Clinical Diagnosis

A complete medical history should be obtained, including symptoms of TB disease, previous TB disease and treatment, previous history of infection with M. tuberculosis, and previous treatment of LTBI or exposure to persons with TB disease. A physical examination should be performed, including chest radiograph, microscopic examination, culture, and, when indicated, NAA testing of sputum (39,53,125,126). If possible, sputum induction with aerosol inhalation is preferred, particularly when the patient cannot produce sputum. Gastric aspiration might be necessary for those patients, particularly children, who cannot produce sputum, even with aerosol inhalation (127--130). Bronchoscopy might be needed for specimen collection, especially if sputum specimens have been nondiagnostic and doubt exists as to the diagnosis (90,111, 127,128,131--134).

All patients with suspected or confirmed infectious TB disease should be placed under airborne precautions until they have been determined to be noninfectious (see Supplement, Estimating the Infectiousness of a TB Patient). Adult and adolescent patients who might be infectious include persons who are coughing; have cavitation on chest radiograph; have positive AFB sputum smear results; have respiratory tract disease with involvement of the lung, pleura or airways, including larynx, who fail to cover the mouth and nose when coughing; are not on antituberculosis treatment or are on incorrect antituberculosis treatment; or are undergoing cough-inducing or aerosol-generating procedures (e.g., sputum induction, bronchoscopy, and airway suction) (30,135).

Persons diagnosed with extrapulmonary TB disease should be evaluated for the presence of concurrent pulmonary TB disease. An additional concern in infection control with children relates to adult household members and visitors who might be the source case (136). Pediatric patients, including adolescents, who might be infectious include those who have extensive pulmonary or laryngeal involvement, prolonged cough, positive sputum AFB smears results, cavitary TB on chest radiograph (as is typically observed in immunocompetent adults with TB disease), or those for whom cough-inducing or aerosol-generating procedures are performed (136,137).

Although children are uncommonly infectious, pediatric patients should be evaluated for infectiousness by using the same criteria as for adults (i.e., on the basis of pulmonary or laryngeal involvement). Patients with suspected or confirmed TB disease should be immediately reported to the local public health authorities so that arrangements can be made for tracking their treatment to completion, preferably through a case management system, so that DOT can be arranged and standard procedures for identifying and evaluating TB contacts can be initiated. Coordinate efforts with the local or state health department to arrange treatment and long-term follow-up and evaluation of contacts.

Laboratory Diagnosis

To produce the highest quality laboratory results, laboratories performing mycobacteriologic tests should be skilled in both the laboratory and the administrative aspects of specimen processing. Laboratories should use or have prompt access to the most rapid methods available: 1) fluorescent microscopy and concentration for AFB smears; 2) rapid NAA testing for direct detection of M. tuberculosis in patient specimens (125); 3) solid and rapid broth culture methods for isolation of mycobacteria; 4) nucleic acid probes or high pressure liquid chromatography (HPLC) for species identification; and 5) rapid broth culture methods for drug susceptibility testing. Laboratories should incorporate other more rapid or sensitive tests as they become available, practical, and affordable (see Supplement, Diagnostic Procedures for LTBI and TB Disease) (138,139).

In accordance with local and state laws and regulations, a system should be in place to ensure that laboratories report any positive results from any specimens to clinicians within 24 hours of obtaining the result (139,140). Certain settings perform AFB smears on-site for rapid results (and results should be reported to clinicians within 24 hours) and then send specimens or cultures to a referral laboratory for identification and drug-susceptibility testing. This referral practice can speed the receipt of smear results but delay culture identification and drug-susceptibility results. Settings that cannot provide the full range of mycobacteriologic testing services should contract with their referral laboratories to ensure rapid results while maintaining proficiency for on-site testing. In addition, referral laboratories should be instructed to store isolates in case additional testing is necessary.

All drug susceptibility results on M. tuberculosis isolates should be reported to the local or state health department as soon as these results are available. Laboratories that rarely receive specimens for mycobacteriologic analysis should refer specimens to a laboratory that performs these tests routinely. The reference laboratory should provide rapid testing and reporting. Out-of-state reference laboratories should provide all results to the local or state health department from which the specimen originated.

Special Considerations for Persons Who Are at High Risk for TB Disease or in Whom TB Disease Might Be Difficult to Diagnose

The probability of TB disease is higher among patients who 1) previously had TB disease or were exposed to M. tuberculosis, 2) belong to a group at high risk for TB disease or, 3) have a positive TST or BAMT result. TB disease is strongly suggested if the diagnostic evaluation reveals symptoms or signs of TB disease, a chest radiograph consistent with TB disease, or AFB in sputum or from any other specimen. TB disease can occur simultaneously in immunocompromised persons who have pulmonary infections caused by other organisms (e.g., Pneumocystis jaroveci [formerly P. carinii] and M. avium complex) and should be considered in the diagnostic evaluation of all such patients with symptoms or signs of TB disease (53).

TB disease can be difficult to diagnose in persons who have HIV infection (49) (or other conditions associated with severe suppression of cell mediated immunity) because of nonclassical or normal radiographic presentation or the simultaneous occurrence of other pulmonary infections (e.g., P. jaroveci or M. avium complex) (2). Patients who are HIV-infected are also at greater risk for having extrapulmonary TB (2). The difficulty in diagnosing TB disease in HIVinfected can be compounded by the possible lower sensitivity and specificity of sputum smear results for detecting AFB (53,141) and the overgrowth of cultures with M. avium complex in specimens from patients infected with both M. tuberculosis and M. avium complex. The TST in patients with advanced HIV infection is unreliable and cannot be used in clinical decision making (35,53,142).

For immunocompromised patients who have respiratory symptoms or signs that are attributed initially to infections or conditions other than TB disease, conduct an evaluation for coexisting TB disease. If the patient does not respond to recommended treatment for the presumed cause of the pulmonary abnormalities, repeat the evaluation (see Supplement, Diagnostic Procedures for LTBI and TB Disease). In certain settings in which immunocompromised patients and patients with TB disease are examined, implementing airborne precautions might be prudent for all persons at high risk. These persons include those infected with HIV who have an abnormal chest radiograph or respiratory symptoms, symptomatic foreign-born persons who have immigrated within the previous 5 years from TBendemic countries, and persons with pulmonary infiltrates on chest radiograph, or symptoms or signs of TB disease.

Initiation of Treatment

For patients who have confirmed TB disease or who are considered highly probable to have TB disease, promptly start antituberculosis treatment in accordance with current guidelines (see Supplements, Diagnostic Procedures for LTBI and TB Disease; and Treatment Procedures for LTBI and TB Disease) (31). In accordance with local and state regulations, local health departments should be notified of all cases of suspected TB.

DOT is the standard of care for all patients with TB disease and should be used for all doses during the course of therapy for treatment of TB disease. All inpatient medication should be administered by DOT and reported to the state or local health department. Rates of relapse and development of drug-resistance are decreased when DOT is used (143--145). All patients on intermittent (i.e., once or twice per week) treatment for TB disease or LTBI should receive DOT. Settings should collaborate with the local or state health department on decisions concerning inpatient DOT and arrangements for outpatient DOT (31).

Managing Patients Who Have Suspected or Confirmed TB Disease: Considerations for Special Circumstances and Settings

The recommendations for preventing transmission of M. tuberculosis are applicable to all health-care settings, including those that have been described (Appendix A). These settings should each have independent risk assessments if they are stand-alone settings, or each setting should have a detailed section written as part of the risk assessment for the overall setting.

Minimum Requirements

The specific precautions for the settings included in this section vary, depending on the setting.

Inpatient Settings

Emergency Departments (EDs)

The symptoms of TB disease are usually symptoms for which patients might seek treatment in EDs. Because TB symptoms are common and nonspecific, infectious TB disease could be encountered in these settings. The use of ED-based TB screening has not been demonstrated to be consistently effective (146).

The amount of time patients with suspected or confirmed infectious TB disease spend in EDs and urgent-care settings should be minimized. Patients with suspected or confirmed infectious TB disease should be promptly identified, evaluated, and separated from other patients. Ideally, such patients should be placed in an AII room. When an AII room is not available, use a room with effective general ventilation, and use air cleaning technologies (e.g., a portable HEPA filtration system), if available, or transfer the patient to a setting or area with recommended infectioncontrol capacity. Facility engineering personnel with expertise in heating, ventilation, and air conditioning (HVAC) and air handlers have evaluated how this option is applied to ensure no over pressurization of return air or unwanted alternations exists in design of air flow in the zone.

EDs with a high volume of patients with suspected or confirmed TB disease should have at least one AII room (see TB Risk Assessment). Air-cleaning technologies (e.g., HEPA filtration and UVGI) can be used to increase equivalent air changes per hour (ACH) in waiting areas (Table 1). HCWs entering an AII room or any room with a patient with infectious TB disease should wear at least an N95 disposable respirator. After a patient with suspected or confirmed TB disease exits a room, allow adequate time to elapse to ensure removal of M. tuberculosis-contaminated room air before allowing entry by staff or another patient (see Environmental Controls; Tables 1 and 2).

Before a patient leaves an AII room, perform an assessment of 1) the patient's need to discontinue airborne precautions, 2) the risk for transmission and the patient's ability to observe strict respiratory hygiene, and 3) cough etiquette procedures. Patients with suspected or confirmed infectious TB who are outside an AII room should wear a surgical or procedure mask, if possible. Patients who cannot tolerate masks because of medical conditions should observe strict respiratory hygiene and cough etiquette procedures.

Intensive Care Units (ICUs)

Patients with infectious TB disease might become sick enough to require admission to an ICU. Place ICU patients with suspected or confirmed infectious TB disease in an AII room, if possible. ICUs with a high volume of patients with suspected or confirmed TB disease should have at least one AII room (see TB Risk Assessment Worksheet) [Appendix B]. Air-cleaning technologies (e.g., HEPA filtration and UVGI) can be used to increase equivalent ACH in waiting areas (see Environmental Controls).

HCWs entering an AII room or any room with a patient with infectious TB disease should wear at least an N95 disposable respirator. To help reduce the risk for contaminating a ventilator or discharging M. tuberculosis into the ambient air when mechanically ventilating (i.e., with a ventilator or manual resuscitator) a patient with suspected or confirmed TB disease, place a bacterial filter on the patient's endotracheal tube (or at the expiratory side of the breathing circuit of a ventilator) (147--151). In selecting a bacterial filter, give preference to models specified by the manufacturer to filter particles 0.3 µm in size in both the unloaded and loaded states with a filter efficiency of >95% (i.e., filter penetration of <5%) at the maximum design flow rates of the ventilator for the service life of the filter, as specified by the manufacturer.

Surgical Suites

Surgical suites require special infectioncontrol considerations for preventing transmission of M. tuberculosis. Normally, the direction of airflow should be from the operating room (OR) to the hallway (positive pressure) to minimize contamination of the surgical field. Certain hospitals have procedure rooms with reversible airflow or pressure, whereas others have positive-pressure rooms with a negative pressure anteroom. Surgical staff, particularly those close to the surgical field, should use respiratory protection (e.g., a valveless N95 disposable respirator) to protect themselves and the patient undergoing surgery.

When possible, postpone non-urgent surgical procedures on patients with suspected or confirmed TB disease until the patient is determined to be noninfectious or determined to not have TB disease. When surgery cannot be postponed, procedures should be performed in a surgical suite with recommended ventilation controls. Procedures should be scheduled for patients with suspected or confirmed TB disease when a minimum number of HCWs and other patients are present in the surgical suite, and at the end of the day to maximize the time available for removal of airborne contamination (see Environmental Controls; Tables 1 and 2).

If a surgical suite or an OR has an anteroom, the anteroom should be either 1) positive pressure compared with both the corridor and the suite or OR (with filtered supply air) or 2) negative pressure compared with both the corridor and the suite or OR. In the usual design in which an OR has no anteroom, keep the doors to the OR closed, and minimize traffic into and out of the room and in the corridor. Using additional air-cleaning technologies (e.g., UVGI) should be considered to increase the equivalent ACH. Air-cleaning systems can be placed in the room or in surrounding areas to minimize contamination of the surroundings after the procedure (114) (see Environmental Controls).

Ventilation in the OR should be designed to provide a sterile environment in the surgical field while preventing contaminated air from flowing to other areas in the health-care setting. Personnel steps should be taken to reduce the risk for contaminating ventilator or anesthesia equipment or discharging tubercle bacilli into the ambient air when operating on a patient with suspected or confirmed TB disease (152). A bacterial filter should be placed on the patient's endotracheal tube (or at the expiratory side of the breathing circuit of a ventilator or anesthesia machine, if used) (147--151). When selecting a bacterial filter, give preference to models specified by the manufacturer to filter particles 0.3 µm in size in both the unloaded and loaded states with a filter efficiency of >95% (i.e., filter penetration of <5%) at the maximum design flow rates of the ventilator for the service life of the filter, as specified by the manufacturer.

When surgical procedures (or other procedures that require a sterile field) are performed on patients with suspected or confirmed infectious TB, respiratory protection should be worn by HCWs to protect the sterile field from the respiratory secretions of HCWs and to protect HCWs from the infectious droplet nuclei generated from the patient. When selecting respiratory protection, do not use valved or positive-pressure respirators, because they do not protect the sterile field. A respirator with a valveless filtering facepiece (e.g., N95 disposable respirator) should be used.

Postoperative recovery of a patient with suspected or confirmed TB disease should be in an AII room in any location where the patient is recovering (118). If an AII or comparable room is not available for surgery or postoperative recovery, air-cleaning technologies (e.g., HEPA filtration and UVGI) can be used to increase the number of equivalent ACH (see Environmental Controls); however, the infectioncontrol committee should be involved in the selection and placement of these supplemental controls.

Laboratories

Staff who work in laboratories that handle clinical specimens encounter risks not typically present in other areas of a health-care setting (153--155). Laboratories that handle TB specimens include 1) pass-through facilities that forward specimens to reference laboratories for analysis; 2) diagnostic laboratories that process specimens and perform acid-fast staining and primary culture for M. tuberculosis; and 3) facilities that perform extensive identification, subtyping, and susceptibility studies.

Procedures involving the manipulation of specimens or cultures containing M. tuberculosis introduce additional substantial risks that must be addressed in an effective TB infection-control program. Personnel who work with mycobacteriology specimens should be thoroughly trained in methods that minimize the production of aerosols and undergo periodic competency testing to include direct observation of their work practices. Risks for transmission of M. tuberculosis in laboratories include aerosol formation during any specimen or isolate manipulation and percutaneous inoculation from accidental exposures. Biosafety recommendations for laboratories performing diagnostic testing for TB have been published (74,75,138,156,157).

In laboratories affiliated with a health-care setting (e.g., a hospital) and in free-standing laboratories, the laboratory director, in collaboration with the infectioncontrol staff for the setting, and in consultation with the state TB laboratory, should develop a risk-based infectioncontrol plan for the laboratory that minimizes the risk for exposure to M. tuberculosis. Consider factors including 1) incidence of TB disease (including drug-resistant TB) in the community and in patients served by settings that submit specimens to the laboratory, 2) design of the laboratory, 3) level of TB diagnostic service offered, 4) number of specimens processed, and 5) whether or not aerosol-generating or aerosol-producing procedures are performed and the frequency at which they are performed. Referral laboratories should store isolates in case additional testing is necessary.

Biosafety level (BSL)-2 practices and procedures, containment equipment, and facilities are required for nonaerosol-producing manipulations of clinical specimens (e.g., preparing direct smears for acid-fast staining when done in conjunction with training and periodic checking of competency) (138). All specimens suspected of containing M. tuberculosis (including specimens processed for other microorganisms) should be handled in a Class I or II biological safety cabinet (BSC) (158,159). Conduct all aerosol-generating activities (e.g., inoculating culture media, setting up biochemical and antimicrobic susceptibility tests, opening centrifuge cups, and performing sonication) in a Class I or II BSC (158).

For laboratories that are considered at least medium risk (Appendix C), conduct testing for M. tuberculosis infection at least annually among laboratorians who perform TB diagnostics or manipulate specimens from which M. tuberculosis is commonly isolated (e.g., sputum, lower respiratory secretions, or tissues) (Appendix D). More frequent testing for M. tuberculosis is recommended in the event of a documented conversion among laboratory staff or a laboratory accident that poses a risk for exposure to M. tuberculosis (e.g., malfunction of a centrifuge leading to aerosolization of a sample).

Based on the risk assessment for the laboratory, employees should use personal protective equipment (including respiratory protection) recommended by local regulations for each activity. For activities that have a low risk for generating aerosols, standard personal protective equipment consists of protective laboratory coats, gowns, or smocks designed specifically for use in the laboratory. Protective garments should be left in the laboratory before going to nonlaboratory areas.

For all laboratory procedures, disposable gloves should be worn. Gloves should be disposed of when work is completed, the gloves are overtly contaminated, or the integrity of the glove is compromised. Local or state regulations should determine procedures for the disposal of gloves. Face protection (e.g., goggles, full-facepiece respirator, face shield, or other splatter guard) should also be used when manipulating specimens inside or outside a BSC. Use respiratory protection when performing procedures that can result in aerosolization outside a BSC. The minimum level of respiratory protection is an N95 filtering facepiece respirator. Laboratory workers who use respiratory protection should be provided with the same training on respirator use and care and the same fit testing as other HCWs.

After documented laboratory accidents, conduct an investigation of exposed laboratory workers. Laboratories in which specimens for mycobacteriologic studies (e.g., AFB smears and cultures) are processed should follow the AIA and CDC/National Institute of Health guidelines (118,159) (see Environmental Controls). BSL-3 practices, containment equipment, and facilities are recommended for the propagation and manipulation of cultures of M. tuberculosis complex (including M. bovis) and for animal studies in which primates that are experimentally or naturally infected with M. tuberculosis or M. bovis are used. Animal studies in which guinea pigs or mice are used can be conducted at animal BSL-2. Aerosol infection methods are recommended to be conducted at BSL-3 (159).

Bronchoscopy Suites

Because bronchoscopy is a cough-inducing procedure that might be performed on patients with suspected or confirmed TB disease, bronchoscopy suites require special attention (29,81,160,161). Bronchoscopy can result in the transmission of M. tuberculosis either through the airborne route (29,63,81,86,162) or a contaminated bronchoscope (80,82,163--170). Closed and effectively filtered ventilatory circuitry and minimizing opening of such circuitry in intubated and mechanically ventilated patients might minimize exposure (see Intensive Care Units) (149).

If possible, avoid bronchoscopy on patients with suspected or confirmed TB disease or postpone the procedure until the patient is determined to be noninfectious, by confirmation of the three negative AFB sputum smear results (109--112). When collection of spontaneous sputum specimen is not adequate or possible, sputum induction has been demonstrated to be equivalent to bronchoscopy for obtaining specimens for culture (110). Bronchoscopy might have the advantage of confirmation of the diagnosis with histologic specimens, collection of additional specimens, including post bronchoscopy sputum that might increase the diagnostic yield, and the opportunity to confirm an alternate diagnosis. If the diagnosis of TB disease is suspected, consideration should be given to empiric antituberculosis treatment.

A physical examination should be performed, and a chest radiograph, microscopic examination, culture, and NAA testing of sputum or other relevant specimens should also be obtained, including gastric aspirates (125), as indicated (53,126,131,130). Because 15%--20% of patients with TB disease have negative TST results, a negative TST result is of limited value in the evaluation of the patient with suspected TB disease, particularly in patients from high TB incidence groups in whom TST positive rates exceed 30% (31).

Whenever feasible, perform bronchoscopy in a room that meets the ventilation requirements for an AII room (same as the AIA guidelines parameters for bronchoscopy rooms) (see Environmental Controls). Air-cleaning technologies (e.g., HEPA filtration and UVGI) can be used to increase equivalent ACH.

If sputum specimens must be obtained and the patient cannot produce sputum, consider sputum induction before bronchoscopy (111). In a patient who is intubated and mechanically ventilated, minimize the opening of circuitry. At least N95 respirators should be worn by HCWs while present during a bronchoscopy procedure on a patient with suspected or confirmed infectious TB disease. Because of the increased risk for M. tuberculosis transmission during the performance of bronchoscopy procedures on patients with TB disease, consider using a higher level of respiratory protection than an N95 disposable respirator (e.g., an elastomeric full-facepiece respirator or a powered air-purifying respirator [PAPR] [29]) (see Respiratory Protection).

After bronchoscopy is performed on a patient with suspected or confirmed infectious TB disease, allow adequate time to elapse to ensure removal of M. tuberculosis--contaminated room air before performing another procedure in the same room (see Environmental Controls; Tables 1 and 2). During the period after bronchoscopy when the patient is still coughing, collect at least one sputum for AFB to increase the yield of the procedure. Patients with suspected or confirmed TB disease who are undergoing bronchoscopy should be kept in an AII room until coughing subsides.

Sputum Induction and Inhalation Therapy Rooms

Sputum induction and inhalation therapy induces coughing, which increases the potential for transmission of M. tuberculosis (87,88,90). Therefore, appropriate precautions should be taken when working with patients with suspected or confirmed TB disease. Sputum induction procedures for persons with suspected or confirmed TB disease should be considered after determination that self-produced sputum collection is inadequate and that the AFB smear result on other specimens collected is negative. HCWs who order or perform sputum induction or inhalation therapy in an environment without proper controls for the purpose of diagnosing conditions other than TB disease should assess the patient's risk for TB disease.

Cough-inducing or aerosol-generating procedures in patients with diagnosed TB should be conducted only after an assessment of infectiousness has been considered for each patient and should be conducted in an environment with proper controls. Sputum induction should be performed by using local exhaust ventilation (e.g., booths with special ventilation) or alternatively in a room that