0
Clinical Investigations: TECHNIQUES |

Predicting Culture Results for Mycobacterium Tuberculosis Complex*: Amplified Mycobacterium Tuberculosis Direct Test and Acid-Fast Bacilli Microscopy FREE TO VIEW

Massimo Gallina, MD; Panaiota Troupioti, MD; Gaetano Rocco, MD, FCCP; Giancarlo Sensalari, MD; Elena Libanori, BS
Author and Funding Information

*From the Microbiology Department (Drs. Gallina, Troupioti, Sensalari, and Ms. Libanori), Division of General Thoracic Surgery (Dr. Rocco), Azienda Ospedaliera Eugenio Morelli, Sondalo, Italy.

Correspondence to: Massimo Gallina, MD, Laboratorio di Analisi Chimico-Cliniche e Microbiologia, Azienda Ospedaliera Eugenio Morelli, Via Zubiani 33, 23039 Sondalo (SO), Italy; e-mail: laborat@novanet.it



Chest. 2000;118(1):28-32. doi:10.1378/chest.118.1.28
Text Size: A A A
Published online

Study objective: To evaluate the usefulness of the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (AMTDT; Gen-Probe; San Diego, CA) in predicting the results of cultures in routine laboratory analysis of a patient population with a high incidence of tuberculosis (TB).

Patients: Three hundred ten patients suspected of pulmonary mycobacterial infection or receiving antituberculous chemotherapy, accrued between 1996 and 1997.

Setting: Tertiary-care facility located in Northern Italy.

Design: We retrospectively compared the AMTDT results with the results of cultures. AMTDT results were also compared with those of acid-fast bacilli (AFB) staining of the same specimens. The study included 360 respiratory specimens from 310 patients collected between 1996 and 1997. In 1996, we used the initial version of AMTDT (50 μL of sediment); in 1997, we used the new version of AMTDT (450 μL of sediment).

Results: Compared with cultures, AMTDT and AFB staining had sensitivities of 87.2% and 68.4%, and specificities of 70.0% and 89.7%, respectively. When AMTDT and AFB staining were both positive, the sensitivity and specificity were 89.3% and 96.9%, respectively. When AMTDT and AFB staining were in disagreement, the sensitivity and specificity of AMTDT were 81.8% and 18.1%, respectively.

Conclusion: We conclude that when AMTDT is used to predict culture outcome, the results should be evaluated in conjunction with AFB staining results before making decisions about TB management.

Cultures of respiratory specimens are frequently scrutinized for Mycobacterium tuberculosis (MT) complex to identify the cause of a pulmonary pathology, as well as to demonstrate the efficacy of a given therapy and to determine when a patient undergoing treatment is no longer contagious. Respiratory specimens are also cultured to test the sensitivity of MT to antimycobacterial drugs. Unfortunately, even when using the most modern methods, the results of culture examinations are only available after 7 to 12 days in the case of a positive result, whereas a negative result is only reliable after 8 to 12 weeks.1 This long incubation period creates an excessive turnaround time between a tentative clinical diagnosis and an indication of the correct treatment, making the management of pulmonary tuberculosis (TB) difficult. Decisions made by the clinician may result in a patient receiving a delayed diagnosis or, alternatively, an unnecessary administration of antituberculosis drugs.1 In addition, some clinicians, fearing that there will be insufficient culture data to form a definitive diagnosis following weeks of waiting, may habitually oversubmit samples, which could lead to an inefficient use of laboratory resources.

Previously, the only rapid test for predicting the outcome of cultures has been the detection of acid-fast bacilli (AFB) using microscopy. More recently, however, the in vitro nucleic acid direct amplification tests (DATs), such as the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (AMTDT; Gen-Probe; San Diego, CA) have been heralded as being more efficient. These tests initially aroused great enthusiasm, due to their higher sensitivity and specificity26; but the expectation that DATs would supplant AFB microscopy, accurately predict culture results, and provide an immediate definitive diagnosis was premature, and has been replaced with a more realistic view of the limitations and practical value of molecular diagnostics for TB.7

While culture results remain the “gold standard” for the presence of mycobacteria in a specimen during diagnosis and follow up,1,811 the clinical applications of AMTDTs must still be discussed and defined.79,12 With a view to optimizing DATs and sample number without compromising diagnostic accuracy, in the present article we evaluate the simultaneous use of AMTDT and AFB microscopy as routine laboratory procedures to predict culture results.

Patients and Specimens

All clinical specimens were collected in the Division of Phtisiology of the Eugenio Morelli Hospital, Italy. One hundred seventy-five respiratory specimens (sputum, 124; bronchial aspirates, 44; BAL, 7) were collected from 125 patients in 1996, and 287 respiratory specimens (sputum, 222; bronchial aspirates, 60; BAL, 5) were collected from 185 patients in 1997. These patients were suspected of pulmonary mycobacterial infection or were receiving antituberculosis chemotherapy. Approximately 10% of patients used in this study were infected with both TB and HIV; 20% were suspected of being infected with TB (diagnosis pending); 50% were being treated for clinically active TB; and 20% had TB that was not clinically active (previously active disease). For this particular patient population, the percent of culture-positive specimens was high (32.8%). The occurrence of low-grade (≤ 50 cfu/slant) culture-positive specimens was 15.8%.

Decontamination Procedures

Respiratory specimens were digested and decontaminated by the N-acetyl-L-cysteine sodium hydroxide method and neutralized with 67 mM phosphate buffer (pH, 6.8). After centrifugation (4,000g for 15 min), the precipitate was resuspended in 2 mL of sterile phosphate buffer. One aliquot of precipitate was used for solid medium culture and a second for AFB staining; a third aliquot was stored for up to 1 week at − 20°C until the AMTDT could be performed.

Cultures

A 0.2-mL precipitate for each slant was used to inoculate two International Union of TB Medium (IUTM) slants (prepared in our laboratory13) that were incubated at 37°C. The precipitate was spread homogeneously over the entire surface of the tubed medium using a serologic pipette. Slants were inspected for growth weekly for 8 weeks. All isolates were confirmed to be MT complex organisms using the Bactec p-nitro-α-acetylamino-§-hydroxypropiophenone test (Becton Dickenson Microbiology Systems; Sparks, MD) or the Accuprobe DNA hybridization assay (Gen-Probe). For each positive culture, the number of mycobacterial colonies and growth time were recorded, according by standard methods.14 Cultures were categorized as high- grade culture-positive (> 50 cfu), low-grade culture-positive (≤ 50 cfu), or as culture-negative. Negative cultures were recorded as such at the end of the eighth week, but were checked weekly until the end of 12 weeks.

AFB Microscopy

One hundred microliters of precipitate were smeared on a slide to cover an area of approximately 1 × 2 cm. Smears were stained with auramine (TB Fluorescent Stain Kit M; Difco Laboratories; Detroit, MI) and observed at 200× magnification. Semiquantitative reporting of smear results were graded following the methods of Kent and Kubica.14

AMTDT

AMTDT has been used routinely in this laboratory since November 1995, when requested by our Division of Phtisiology, following the protocols as supplied by the manufacturer. In 1996, we used the original version (50 μL of processed sediment: AMTDT 1). In 1997, we used the new protocol (450 μL of sediment: AMTDT 2).15 All runs of AMTDT 1 included positive and negative controls for both amplification and hybridization; for AMTDT 2, only positive and negative controls of amplification were included. Results were read with a Berthold luminometer (LUMAT LB 9501; Laboratorium Prof. Berthold GmbH & Co.KG; Bad Wildbad, Germany). As specified by the Gen-Probe protocol for AMTDT 1, samples with > 500,000 relative light units (RLU) were considered positive; samples with < 30,000 RLU were recorded as negative, and samples with values between 30,000 and 500,000 RLU were recorded as undetermined. For AMTDT 2, however, samples with > 30,000 RLU were recorded as positive, whereas samples with values of < 30,000 RLU were considered negative.

For each specimen, results from an AMTDT were compared with those of AFB staining and the number of colony-forming units of MT complex obtained on the IUTM slants.

Fifty-seven of the 175 specimens collected in 1996 and 45 of the 287 specimens collected in 1997 were excluded from this study for the following reasons: cultures were overgrown with nonacid-fast organisms (30 in 1996, 30 in 1997); cultures were positive for nontuberculous mycobacteria (NTM; 8 in 1996, 15 in 1997); and AMTDT result was undetermined (34 in 1996). Consequently, the specimens included in this analysis were 118 from 1996 and 242 from 1997.

A total of 117 cultures were recovered from 360 specimens; among them, 60 produced > 50 colonies on the slant, and 57 produced < 50 colonies. The fraction of specimens in the three categories was not significantly different between the two study years (χ2 test, p = 0.57).

The results of IUTM cultures, AFB microscopy, and AMTDT from both study years are summarized in Tables 123 . In each category in Tables 1,2, for which there were two or more samples in both years, a χ2 test was performed. No significant differences were observed for any category for the two study years; therefore, data from both years were pooled.

The AFB-positive smear + category was considered separately from the categories ++ to ++++, because the fraction of high-grade/low-grade culture-positive specimens in this category (5/14) was significantly different from the other three: ++, 20/4; +++, 18/6; and ++++, 10/3;χ 2 test, p < 0.001).

Of 60 high-grade culture-positive samples (> 50 cfu), 7 AFB smears and 3 AMTDTs yielded false-negatives. Of 57 low-grade culture-positive samples (≤ 50 cfu), 19 were AFB smear negative, 11 were AFB smear ± (doubtful), and 12 were AMTDT negative. Overall, for the 243 culture-negative samples, AFB smears yielded 10 false-positives (4.1%), whereas AMTDT yielded 73 false-positives (30.0%).

AMTDT was positive in 102 of 117 total positive cultures (sensitivity, 87.2%), in 57 of 60 high-grade positive cultures (sensitivity, 95.0%), and in 45 of 57 low-grade positive cultures (sensitivity, 78.9%). AMTDT was negative for 170 of 243 negative cultures (specificity, 70.0%).

AFB smear was positive in 80 of 117 total positive cultures (sensitivity, 68.4%), in 53 of 60 high-grade positive cultures (sensitivity, 88.3%), and in 27 of 57 low-grade positive cultures (sensitivity, 47.4%). AFB smears were negative for 218 of 243 negative cultures (specificity, 89.7%).

Not considering results in which AMTDT and AFB smear were contradictory or AFB smears were ± (doubtful), AMTDT and AFB smears were both positive for 75 of 84 total positive cultures (sensitivity, 89.3%), in 51 of 52 high-grade positive cultures (sensitivity, 98.1%), and in 24 of 32 low-grade positive cultures (sensitivity, 75.0%). The specificity was 96.8% (155 of 160). Both these tests were negative for 9 of 117 total positive cultures (7.7% false-negatives), and in only 1 of 60 high-grade positive cultures (1.7% false-negatives). For 5 of 243 culture-negative specimens, AMTDT and AFB smear were both positive (2.1% false-positives).

Of 116 specimens for which AMTDT and AFB smear results were contradictory, or AFB smear results were ± (doubtful), AMTDT was positive in 27 of 33 total positive cultures (sensitivity, 81.8%), and in 6 of 8 high-grade positive cultures (sensitivity, 75.1%). AMTDT was negative in 15 of 83 negative cultures (specificity, 18.1%).

Table 4 summarizes various predictive values of AMTDT with different AFB smear results. Rates of positivity on culture range from 92.4% for ++ to++++ AFB-positive smears to 10.6% for AFB-negative smears. The maximum positive predictive value (PPV) was obtained when AFB smears were positive ++ or higher. A PPV of 88.9 was obtained for AFB-positive + smears. Elevated negative predictive values (NPVs) were obtained for AFB-± (doubtful) smears and AFB-negative specimens (90.9% and 94.5%, respectively).

The present study was conducted with a large number of respiratory specimens examined under routine laboratory conditions using conventional and molecular methods in parallel, as suggested by Roth et al.7 We found the addition of AMTDT to the routine work in our laboratory to be uncomplicated: the assay was easy to perform and no major technical problems occurred.

In contrast to Gamboa et al,15 we did not find differences in sensitivity between the two protocols of AMTDT provided by Gen-Probe (AMTDT 1, 85% [34 of 40]; AMTDT 2, 88.3% [68 of 77];χ 2 test, p = 0.61). Nonetheless, an advantage of AMTDT 2 is that it never yielded undetermined results, while 19.6% (34 of 175) of samples in 1996 were of this type.

Our study shows that when AMTDT is applied to a patient population like the one described, it has questionable specificity and limited sensitivity in predicting culture results. Previous studies have shown that the sensitivity of AMTDT depends on the number of bacilli in the specimen16,3,7; likewise, we found in our study that AMTDT was more likely to detect MT in specimens with > 50 cfu/slant. In fact, the sensitivity of AMTDT increases from 78.9% in specimens with≤ 50 cfu/slant to 95% in specimens with > 50 cfu/slant. The sensitivity of AMTDT is also influenced by the number of specimens containing inhibitors. Although inhibitors are relatively rare, they are also unpredictable.12 In this study, only two specimens were AMTDT negative when the respective AFB-positive smear was +++ and the culture had > 50 cfu/slant, presumably because the specimens contained inhibitors. However, in clinical specimens, a low degree of positivity, sample inhomogeneity, inhibitors, and/or effects of sample processing may decrease the sensitivity of the test.1,17 For these reasons, there is a need to improve sample collection and processing. In this setting, a test for inhibitors needs to be performed to better assist in determining the value of a negative AMTDT result.

Our results confirm that AMTDT can detect inviable organisms, as noted previously.7,16 In the present patient population, there were many patients undergoing antimycobacterial treatment; consequently, the low specificity of the test indicates that AMTDT is not particularly suitable for the rapid assessment of treatment efficacy.16

In this mixed patient population, and without considering NTM, AFB microscopy showed a higher specificity (89.7%) in predicting culture results than AMTDT, but a lower sensitivity.

When AMTDT and AFB smear results are concordant, the high specificity of AFB microscopy decreases the overall fraction of false-positives. In particular, when AFB smears are positive ++ to ++++, and AMTDT is positive, PPV is also high (95.2%). In our opinion, the clinician could consider this result a sufficient guarantee of correct sampling and can expect, in most cases, to obtain a positive culture result. She/he could confidently use this result to make management decisions, and, where required, the culture could most probably be used for drug sensitivity tests. In addition, this result should persuade the clinician to limit the number of successive samples to be analyzed, as suggested by several authors,1819 to as few as two, thereby avoiding an inefficient use of laboratory resources.

The high specificity obtained when AMTDT results were in agreement with the AFB smear has also been noted by previous authors.1,10 However, we found that when a positive AMTDT result is associated with an AFB-positive + smear, the possibility of a negative culture rises to about 10%. Samples with such a combination of results may have low numbers of MT and, consequently, the possibility of a negative culture (or a positive one only after prolonged incubation) is high, and it would be wise for the clinician to send further samples to the laboratory.

A negative AFB smear associated with a negative AMTDT has a high NPV (94.5%) in predicting the culture result. This combination of results indicates that the possibility of a positive culture is very low, and in any case, a longer growth time is expected.

When the results obtained from AMTDT and AFB smear are in disagreement, the sensitivity of AMTDT is still acceptable (81.8%), but its specificity (18.1%) means the predictive value is almost nil. In this case, the clinician has no choice but to send better quality specimens for reevaluation. However, if the AMTDT is negative in the presence of an AFB-positive ++++ smear, the presence of inhibitors or NTM can be suspected.

If the AFB smear is negative and AMTDT is positive, the probability of a negative culture increases. In this case, the clinician should verify if an antimycobacterial therapy is or has been administrated to the patient. In fact, AMTDT can remain positive many months after the initiation or completion of therapy.8 For this reason, one author12 has proposed that AMTDT only be used for untreated patients.

In conclusion, when AMTDT is requested to predict the outcome of a culture under routine laboratory conditions, we would recommend that this test always be used in association with the semiquantitative AFB smear to be sure that the specimen gives useful information for the management of TB.

Abbreviations: AFB = acid-fast bacilli; AMTDT = Amplified Mycobacterium Tuberculosis Direct Test; DAT = direct amplification test; IUTM = International Union of TB Medium; MT = Mycobacterium tuberculosis; NTM = nontuberculous mycobacteria; NPV = negative predictive value; PPV = positive predictive value; RLU = relative light units; TB = tuberculosis

This work was performed in the Hospital Azienda Ospedaliera Eugenio Morelli, Sondalo, Italy.

Table Graphic Jump Location
Table 1. Results of Cultures and AMTDTs*
* 

Data are given as No.

 

Range, 1 to 20 cfu.

 

Range, 100 to 200 cfu.

Table Graphic Jump Location
Table 2. Results of Cultures and AFB Smears*
* 

Data are given as No.

Table Graphic Jump Location
Table 3. Results of Cultures vs AMTDTs and AFB Smears*
* 

Data are given as No.

Table Graphic Jump Location
Table 4. Predictive Values of AMTDT in Specimens With Different AFB Smear Results
* 

Rates of positivity on culture.

We are grateful to Heidi Hauffe for helping with the translation of this manuscript.

Bradley, SP, Reed, SL, Catanzaro, A (1996) Clinical efficacy of the amplifiedMycobacterium tuberculosisdirect test for the diagnosis of pulmonary tuberculosis.Am J Respir Crit Care Med153,1606-1610. [PubMed]
 
Abe, C, Hirano, K, Wada, M, et al Detection ofMycobacterium tuberculosisin clinical specimens by polymerase chain reaction and Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test.J Clin Microbiol1993;31,3270-3274. [PubMed]
 
Jonas, V, Alden, MJ, Curry, JI, et al Detection and identification ofMycobacterium tuberculosisdirectly from sputum sediments by amplification of rRNA.J Clin Microbiol1993;31,2410-2416. [PubMed]
 
La Rocco, MT, Wanger, A, Ocera, H, et al Evaluation of a commercial rRNA amplification assay for direct detection ofMycobacterium tuberculosisin processed sputum.Eur J Microbiol Infect Dis1994;13,726-731. [CrossRef]
 
Miller, N, Hernandez, SG, Cleary, TJ Evaluation of Gen-probe AmplifiedMycobacterium tuberculosisDirect Test and PCR for direct detection ofMycobacterium tuberculosisin clinical specimens.J Clin Microbiol1994;32,393-397. [PubMed]
 
Pfyffer, GE, Kissling, P, Wirth, R, et al Direct detection ofMycobacterium tuberculosiscomplex in respiratory specimens by target-amplified test system.J Clin Microbiol1994;32,918-923. [PubMed]
 
Roth, A, Schaberg, T, Mauch, H Molecular diagnosis of tuberculosis: current clinical validity and future perspectives.Eur Respir J1997;10,1877-1891. [CrossRef] [PubMed]
 
Catanzaro, A, Davidson, BL, Fujiwara, PI, et al Rapid diagnostic tests for tuberculosis. What is the appropriate use?Am J Respir Crit Care Med1997;155,1804-1814. [PubMed]
 
Ichiyama, S, Iinuma, Y, Tawada, Y, et al Evaluation of Gen-Probe amplifiedMycobacterium tuberculosisdirect test and Roche PCR-microwell plate hybridization method (Amplicor Mycobacterium) for direct detection of mycobacteria.J Clin Microbiol1996;34,130-133. [PubMed]
 
Lebrun, L, Mathieu, D, Saulinier, C, et al Limits of commercial molecular tests for diagnosis of pulmonary tuberculosis.Eur Respir J1997;10,1874-1876. [CrossRef] [PubMed]
 
Tenover, FC, Crawford, JT, Huebner, RE, et al The resurgence of tuberculosis: is your laboratory ready?J Clin Microbiol1993;31,767-770. [PubMed]
 
Fairfax, MR Evaluation of the Gen-Probe amplifiedMycobacterium tuberculosisdirect detection test.Am J Clin Pathol1996;106,594-599. [PubMed]
 
Giorgio A. Manuale di batteriologia clinica. Ragno M, editore. Roma 1980; 80.
 
Kent PT, Kubica GP. Public health mycobacteriology: a guide for the level III laboratory. U.S. Department of Health and Human Services. Atlanta, GA: Centers for Disease Control, 1985.
 
Gamboa, F, Fernandez, G, Padilla, E, et al Comparative evaluation of initial and new version of the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test for direct detection ofMycobacterium tuberculosisin respiratory and nonrespiratory specimens.J Clin Microbiol1998;36,684-689. [PubMed]
 
Bodmer, T, Gurtner, A, Schopfer, K, et al Screening of respiratory tract specimens for the presence ofMycobacterium tuberculosisby using a Gen-Probe amplifiedMycobacterium tuberculosisdirect test.J Clin Microbiol1994;32,1483-1487. [PubMed]
 
Dalovisio, JR, Montenegro-James, S, Kemmerly, SA, et al Comparison of the Amplified Mycobacterium tuberculosis (MTB) Direct Test, Amplicor MTB PCR, and IS6110-PCR for detection of MTB in respiratory specimens.Clin Infect Dis1996;23,1099-1106. [CrossRef] [PubMed]
 
Nelson, SM, Deike, MA, Cartwright, CP Value of examining multiple sputum specimens in the diagnosis of pulmonary tuberculosis.J Clin Microbiol1998;36,467-469. [PubMed]
 
Stone, BL, Burman, WJ, Hildred, MV, et al The diagnostic yield of acid-fast-bacillus smear-positive sputum specimens.J Clin Microbiol1997;35,1030-1031. [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1. Results of Cultures and AMTDTs*
* 

Data are given as No.

 

Range, 1 to 20 cfu.

 

Range, 100 to 200 cfu.

Table Graphic Jump Location
Table 2. Results of Cultures and AFB Smears*
* 

Data are given as No.

Table Graphic Jump Location
Table 3. Results of Cultures vs AMTDTs and AFB Smears*
* 

Data are given as No.

Table Graphic Jump Location
Table 4. Predictive Values of AMTDT in Specimens With Different AFB Smear Results
* 

Rates of positivity on culture.

References

Bradley, SP, Reed, SL, Catanzaro, A (1996) Clinical efficacy of the amplifiedMycobacterium tuberculosisdirect test for the diagnosis of pulmonary tuberculosis.Am J Respir Crit Care Med153,1606-1610. [PubMed]
 
Abe, C, Hirano, K, Wada, M, et al Detection ofMycobacterium tuberculosisin clinical specimens by polymerase chain reaction and Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test.J Clin Microbiol1993;31,3270-3274. [PubMed]
 
Jonas, V, Alden, MJ, Curry, JI, et al Detection and identification ofMycobacterium tuberculosisdirectly from sputum sediments by amplification of rRNA.J Clin Microbiol1993;31,2410-2416. [PubMed]
 
La Rocco, MT, Wanger, A, Ocera, H, et al Evaluation of a commercial rRNA amplification assay for direct detection ofMycobacterium tuberculosisin processed sputum.Eur J Microbiol Infect Dis1994;13,726-731. [CrossRef]
 
Miller, N, Hernandez, SG, Cleary, TJ Evaluation of Gen-probe AmplifiedMycobacterium tuberculosisDirect Test and PCR for direct detection ofMycobacterium tuberculosisin clinical specimens.J Clin Microbiol1994;32,393-397. [PubMed]
 
Pfyffer, GE, Kissling, P, Wirth, R, et al Direct detection ofMycobacterium tuberculosiscomplex in respiratory specimens by target-amplified test system.J Clin Microbiol1994;32,918-923. [PubMed]
 
Roth, A, Schaberg, T, Mauch, H Molecular diagnosis of tuberculosis: current clinical validity and future perspectives.Eur Respir J1997;10,1877-1891. [CrossRef] [PubMed]
 
Catanzaro, A, Davidson, BL, Fujiwara, PI, et al Rapid diagnostic tests for tuberculosis. What is the appropriate use?Am J Respir Crit Care Med1997;155,1804-1814. [PubMed]
 
Ichiyama, S, Iinuma, Y, Tawada, Y, et al Evaluation of Gen-Probe amplifiedMycobacterium tuberculosisdirect test and Roche PCR-microwell plate hybridization method (Amplicor Mycobacterium) for direct detection of mycobacteria.J Clin Microbiol1996;34,130-133. [PubMed]
 
Lebrun, L, Mathieu, D, Saulinier, C, et al Limits of commercial molecular tests for diagnosis of pulmonary tuberculosis.Eur Respir J1997;10,1874-1876. [CrossRef] [PubMed]
 
Tenover, FC, Crawford, JT, Huebner, RE, et al The resurgence of tuberculosis: is your laboratory ready?J Clin Microbiol1993;31,767-770. [PubMed]
 
Fairfax, MR Evaluation of the Gen-Probe amplifiedMycobacterium tuberculosisdirect detection test.Am J Clin Pathol1996;106,594-599. [PubMed]
 
Giorgio A. Manuale di batteriologia clinica. Ragno M, editore. Roma 1980; 80.
 
Kent PT, Kubica GP. Public health mycobacteriology: a guide for the level III laboratory. U.S. Department of Health and Human Services. Atlanta, GA: Centers for Disease Control, 1985.
 
Gamboa, F, Fernandez, G, Padilla, E, et al Comparative evaluation of initial and new version of the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test for direct detection ofMycobacterium tuberculosisin respiratory and nonrespiratory specimens.J Clin Microbiol1998;36,684-689. [PubMed]
 
Bodmer, T, Gurtner, A, Schopfer, K, et al Screening of respiratory tract specimens for the presence ofMycobacterium tuberculosisby using a Gen-Probe amplifiedMycobacterium tuberculosisdirect test.J Clin Microbiol1994;32,1483-1487. [PubMed]
 
Dalovisio, JR, Montenegro-James, S, Kemmerly, SA, et al Comparison of the Amplified Mycobacterium tuberculosis (MTB) Direct Test, Amplicor MTB PCR, and IS6110-PCR for detection of MTB in respiratory specimens.Clin Infect Dis1996;23,1099-1106. [CrossRef] [PubMed]
 
Nelson, SM, Deike, MA, Cartwright, CP Value of examining multiple sputum specimens in the diagnosis of pulmonary tuberculosis.J Clin Microbiol1998;36,467-469. [PubMed]
 
Stone, BL, Burman, WJ, Hildred, MV, et al The diagnostic yield of acid-fast-bacillus smear-positive sputum specimens.J Clin Microbiol1997;35,1030-1031. [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543