CLINICAL COMMUNICATION TO THE EDITOR
Causes of Persistent Acid-Fast Positive
Smears in Pulmonary Tuberculosis
To the Editor:
Three months after initiating chemotherapy for pulmo-
nary tuberculosis, the number of acid-fast bacilli in sputum
smears are negative in more than 95% of cases.1,2 The main
reasons for persistently positive acid-fast smears include
nonadherence to treatment and drug resistance.3 In a small
number of patients with pulmonary tuberculosis who are
receiving effective chemotherapy, the presence of acid-fast
staining organisms in smears are due to nonviable bacilli or
coinfection4 with other acid-fast organisms, and it may not
represent treatment failure.
Funding: None.
Conflict of Interest: None.
Authorship: Both authors had access to the data and played a role in
writing this manuscript.
Requests for reprints should be addressed to Carlos Franco-Paredes,
MD, MPH, Infectious Disease Section, Phoebe Putney Memorial Hospital,
Albany, GA 31721.
E-mail address: cfranco@ppmh.org
Figure Chest computed tomography demonstrating a left
upper lobe infiltrate infiltrating to the lingula.
0002-9343/$ -see front matter © 2012 Elsevier Inc. All rights reserved.
Table 1 Causes of Persistent Acid-Fast Positive Smears in
Patients with Pulmonary Tuberculosis
Drug resistance
Noncompliance or nonadherence to tuberculous chemotherapy
Decreased intestinal absorption of antituberculosis drugs
Coinfection with another acid-fast positive organism
Presence of unviable bacilli
CASE REPORT
We present the case of a 56-year-old human immunodeficiency
virus-seronegative man with active pulmonary tuberculosis. A
chest computed tomography scan showed bilateral pulmonary
infiltrates with a cavitary lesion in the left upper lobe (Figure).
Fluorochrome staining of expectorated sputum revealed the pres-
ence of acid-fast bacilli. Mycobacterium tuberculosis complex
was isolated with susceptibility to all first line-drugs.
The patient received directly observed daily therapy with
the 4-drug regimen for 56 doses. At this point, a clinical
evaluation revealed that the patient continued to experience
night sweats, had a productive cough, and had lost 3 more
pounds. In addition, expectorated sputum revealed large
numbers of acid-fast bacilli. Daily multidrug antituberculo-
sis regimen was continued for a third consecutive month
without any clinical improvement and persistently positive
acid-fast organisms in smears of sputum. Directly observed
therapy records were reviewed, and adherence to medica-
tions was confirmed. To verify intestinal absorption of
drugs, serum levels of rifampin, isoniazid, and ethambutol
were obtained and reported as adequate.
Despite persistently acid-fast positive smears, mycobacte-
rial culture at 2 and 3 months of chemotherapy was reported as
negative. Instead, Rhodococcus equi, an acid-fast staining ba-
cilli sometimes identified in respiratory specimens, was iso-
lated from expectorated sputum. We initiated concomitant
treatment for R. equi with a 3-month regimen of intravenous
vancomycin, imipenem-cilastatin, and levofloxacin.4 One
month later, the patient had significant clinical improvement
and expectorated sputum converted to negative and culture and
remained negative thereafter. Antituberculosis treatment was
continued in the patient, with a continuation phase regimen of
isoniazid and rifampin for 7 months.
DISCUSSION
The institution of tuberculosis chemotherapy has 3 major
goals: to rapidly kill the massive numbers of tuberculosis
e4 The American Journal of Medicine, Vol 125, No 12, December 2012
bacilli present that are multiplying in pulmonary tissue,
to prevent the emergence of clinically significant drug-
resistant strains, and to effectively sterilize the disease
sites.4 In the presence of effective treatment, persistent
acid-fast positivity in smears requires a careful evalua-
tion to identify the cause of the delayed conversion
(Table 1). Treatment failure of pulmonary tuberculosis is
considered with continued or recurrently positive cul-
tures during the course of antituberculosis therapy after 4
months of treatment. However, there are a number of
patients who have delayed conversion of smears.1,2 Prob-
able reasons for delayed conversion or treatment failure
in patients receiving appropriate regimens include non-
adherence to medications, underlying drug resistance,
development of de novo drug resistance, decreased intes-
tinal absorption of drugs, and coinfection with other
acid-fast staining organisms (Table 2).3
Table 2 Acid-Fast Staining Organisms*
Bacterial:
Nocardia spp., Rhodococcus equi, Legionella micdadei,
Tsukamurella spp., Gordonia spp.
Mycobacterial:
Mycobacterium tuberculosis and nontuberculous mycobacteria (ie,
M. kansasii, M. marinum)
Parasitic:
Cryptosporidium spp., Cyclospora cayetanensis, Isospora belli,
Sarcocystis hominis
Fungal:
Blastomyces dermatitidis
*Acid-fast or modified acid-fast staining pattern.
CONCLUSIONS
Our case demonstrates that there are other respiratory patho-
gens that share the acid-fast staining ability of M. tubercu-
losis, including Nocardia spp., Rhodococcus spp. and Le-
gionella micdadei. Therefore, clinicians should be aware of
the potential for misdiagnosis of these organisms with the
tubercle bacilli or the possibility of coinfection among those
with persistently positive acid-fast staining smears.
Carlos Franco-Paredes, MD, MPHa,b,c
Susan Ray, MDd
a
Infectious Disease Clinic
Phoebe Putney Memorial Hospital, Albany, Ga
b
Hospital Infantil de Mexico, Federico Gomez
Mexico City, Mexico
c
Rollins School of Public Health
Emory University, Atlanta, Ga
d
Department of Medicine
Emory University School of Medicine, Atlanta, Ga
http://dx.doi.org/10.1016/j.amjmed.2012.03.002
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