CHEST Selected Reports

Beneficial Response to ties. A diagnosis of desquamative interstitial pneumonia

(DIP) was suspected and was confirmed by a thoraco-
Macrolide Antibiotic in a Patient scopic open lung biopsy (Fig 1). There was no evidence of
With Desquamative Interstitial organizing pneumonia, eosinophilia, or granulomatous in-
flammation. The findings of all cultures of lung tissue,
Pneumonia Refractory to including those for acid-fast bacilli and fungus, were
Corticosteroid Therapy* negative. Pulmonary function testing revealed restrictive
disease of moderate severity (lung volumes were de-
Alexey Knyazhitskiy, MD; Richard G. Masson, MD, FCCP; creased to 62% predicted; single-breath diffusing capacity
Richard Corkey, MD; and Jane Joiner, MD of the lung for carbon monoxide was 40%). The arterial
oxygen saturation was 91% at rest while breathing room
Macrolide antibiotics have been shown to have a
beneficial effect in a number of pulmonary condi-
tions that are characterized by inflammation, includ-
ing cystic fibrosis, asthma, and cryptogenic organizing
pneumonia. We report the first case of desquamative
interstitial pneumonia (DIP) showing a favorable re-
sponse to treatment with clarithromycin. If confirmed,
this observation would add DIP to the list of pulmonary
disorders that are amenable to the beneficial antiin-
flammatory effects of macrolides.
(CHEST 2008; 134:185–187)

Key words: clarithromycin; desquamative interstitial pneumonia;

macrolide

Abbreviation: DIP ⫽ desquamative interstitial pneumonia

T symptoms
he patient, a 56-year-old woman, presented with
of a lower respiratory infection, severe
hypoxemia, and diffuse pulmonary infiltrates seen on a
chest roentgenogram. She was a lifelong smoker whose
medical history was relevant for hypertension, depression,
and type II diabetes mellitus. The initial diagnosis was
severe community-acquired pneumonia with ARDS. She
was treated with a bilevel, positive-airway-pressure mask,
antibiotics, and supportive care, and responded well to
therapy. A 2-year-old chest roentgenogram obtained from
another hospital revealed a similar diffuse lung process. A
CT scan of the chest revealed diffuse ground-glass densi-

*From the Departments of Internal Medicine (Drs. Knyazhitskiy

and Joiner), Pulmonary Medicine (Dr. Masson), and Pathology
(Dr. Corkey), MetroWest Medical Center, Framingham, MA.
The authors have reported to the ACCP that no significant
conflicts of interest exist with any companies/organizations whose
products or services may be discussed in this article.
Manuscript received November 15, 2007; revision accepted
January 3, 2008.
Reproduction of this article is prohibited without written permission
from the American College of Chest Physicians (www.chestjournal.
org/misc/reprints.shtml).
Correspondence to: Alexey Knyazhitskiy, MD, MetroWest Medi-
cal Center, Internal Medicine, 115 Lincoln St, Framingham, MA Figure 1. Lung biopsy specimen. Top, A: both fibrotic and
01702; e-mail: aknyazhitskiy@mwmc.com desquamative aspects are present (hematoxylin-eosin, original ⫻40).
DOI: 10.1378/chest.07-2786 Bottom, B: glycoprotein CD68 (macrophage stain, original ⫻200).

www.chestjournal.org CHEST / 134 / 1 / JULY, 2008 185

air, and 81% after walking 100 feet at a slow pace.
Despite smoking cessation and treatment with pred-
nisone, 1 mg/kg/d, the disease progressed over the next
several months, with worsening restrictive disease seen
on lung function test results, worsening dyspnea and
hypoxemia, and the progression of infiltrates seen on
chest roentgenograms (Fig 2, top, A). The patient’s
oxygen saturation while breathing room air was then
83%. In addition, she became increasingly intolerant to
steroid therapy, with worsening of her diabetes. Exten-
sive lower extremity edema and poorly healing, infected
leg ulcers developed. Because our patient had not
responded to treatment with corticosteroids and signif-
icant steroid morbidity was developing, the prednisone
dosage was decreased to 20 mg/d. Before the institution
of treatment with alternative immunosuppressant
agents, she was treated with clarithromycin, 500 mg
po/bid, based on the reported efficacy of macrolide
antibiotics in other inflammatory lung disorders. The
patient returned for follow-up after 2 weeks of antibi-
otic treatment, and reported a dramatic improvement in
exercise tolerance and the disappearance of her previ-
Figure 2. Chest roentgenograms. Top, A: extensive infiltrates
are seen despite corticosteroid therapy. Bottom, B: substantial
but incomplete resolution is seen after the institution of clarithro-
mycin therapy.
186
ously refractory cough. Her arterial oxygen saturation
was then 97% while breathing room air, falling to 91%
with exercise, and a repeat chest roentgenogram ob-
tained after 28 days of treatment showed partial clear-
ing of the lung infiltrates (Fig 2, bottom, B). Pulmonary
function testing showed improvement in vital capacity
and diffusing capacity of the lung carbon monoxide,
though significant restrictive disease persisted. To date,
our patient has remained in remission for 3 months
while receiving continued macrolide therapy, although
attempts at decreasing the prednisone dosage to ⬍ 20
mg/d have been unsuccessful.
Discussion
DIP is a rare pulmonary disorder that is characterized
by dyspnea, cough, and diffuse ground-glass pulmonary
infiltrates. It is usually associated with current or former
cigarette smoking, and pathology findings shows alveoli
filled with pigment-laden macrophages and varying de-
grees of fibrosis. Patients with DIP frequently show
pathologic changes of respiratory bronchiolitis-associated
interstitial lung disease (RB-ILD), which some believe1
evolves into DIP. There is usually a good clinical response
to smoking cessation with or without treatment with
corticosteroid therapy, and the prognosis is generally
good. However, occasional patients (such as ours) do not
respond to treatment, and overt respiratory failure and
even death develop. Macrolide antibiotics appear to pos-
sess antiinflammatory properties independent of their
antibiotic effect and have been shown to be beneficial in a
number of pulmonary disorders. The most dramatic of
these disorders is diffuse panbronchiolitis, which is a
severe, progressive inflammatory lung disorder that is
almost unique to Japan.2 The prognosis for patients with
this disorder is grave, and many patients die of respiratory
failure. Erythromycin has revolutionized the treatment of
this previously frequently fatal disorder. Studies3 have also
shown the beneficial effects of therapy with macrolide
antibiotics in patients with cystic fibrosis, asthma, and
bronchiectasis not due to cystic fibrosis. Limited studies in
patients with cryptogenic organizing pneumonia4 and
bronchiolitis obliterans syndrome after transplantation5
have also shown beneficial responses. Although the exact
mechanism for the beneficial effect of therapy with mac-
rolide antibiotics in these disorders has not been com-
pletely clarified, it is clearly not related to their antibiotic
properties. Treatment with macrolides has been associated
with a decrease in cytokines in BAL fluid, mucus produc-
tion, and neutrophil influx.6 Macrolides may also have a
protective effect on the airways epithelium.7 Based on
these previous observations, we decided to institute a brief
therapeutic trial of clarithromycin in our patient. The
rapid and dramatic improvement in all clinical and radio-
graphic parameters in the absence of evidence of any
infectious process is strong evidence for a beneficial effect
of macrolide antibiotic therapy in patients with DIP.
Conclusion
Although it is impossible to draw broad clinical conclu-
sions from results in a single case, the dramatic clinical
Selected Reports
improvement seen in our patient, temporally related to
treatment with macrolide antibiotics, suggests a possible
role for these antibiotics in the treatment of DIP. Although
further study with a larger number of patients is needed, a
short therapeutic trial of a macrolide antibiotic is an easy
intervention with low morbidity and might be a consideration
prior to the institution of more potent immunosuppressive
therapy in newly diagnosed patients with DIP.
References
1 Ryu JH, Myers JL, Capizzi SA, et al. Desquamative interstitial
pneumonia and respiratory bronchiolitis-associated lung dis-
ease. Chest 2005; 127:178 –184
2 Kudoh S, Uetake T, Hagiwara K, et al. Clinical effect of low-dose
long-term erythromycin chemotherapy on diffuse panbronchiol-
itis. Nihon Kyobu Shikkan Gakkai Zasshi 1987; 25:632– 642
3 Garey KW, Alwani A, Danziger LH, et al. Tissue reparative
effects of macrolide antibiotics in chronic inflammatory si-
nopulmonary diseases. Chest 2003; 123:261–265
4 Stover DE, Mangino D. A treatment alternative for bronchiolitis
obliterans organizing pneumonia? Chest 2005; 128:3611–3617
5 Yates B, Murphy DM, Forrest IA, et al. Azithromycin reverses
airflow obstruction in established bronchiolitis obliterans syn-
drome. Am J Respir Crit Care Med 2005; 172:772–775
6 Rubin KB, Henke MO. Immunomodulatory activity and and
effectiveness of macrolides in chronic airway disease. Chest
2004; 125(suppl):70S–78S
7 Wales D, Woodhead M. The anti-inflammatory effects of
macrolides. Thorax 1999; 54:58 – 62
Case Series Report of a
Linezolid-Containing Regimen
for Extensively Drug-Resistant
Tuberculosis*
Rany Condos, MD; Nicos Hadgiangelis, MD†;
Eric Leibert, MD, FCCP; Germaine Jacquette, MD;
Timothy Harkin, MD, FCCP‡;
and William N. Rom, MD, MPH, FCCP
Objective: To determine whether linezolid is safe
and well tolerated in the treatment of extensively
drug-resistant tuberculosis (XDR-TB).
Materials and methods: The was conducted in a
*From the Division of Pulmonary and Critical Care Medicine,
New York University School of Medicine, New York, NY.
†Current address: Odyssey House, New York, NY.
‡Current address: Division of Pulmonary and Critical Care
Medicine, Mt. Sinai School of Medicine, New York, NY.
The authors have reported to the ACCP that no significant
conflicts of interest exist with any companies/organizations whose
products or services may be discussed in this article.
Manuscript received August 23, 2007; revision accepted January
9, 2008.
Reproduction of this article is prohibited without written permission
from the American College of Chest Physicians (www.chestjournal.
org/misc/reprints.shtml).
Correspondence to: Rany Condos, MD, Bellevue Chest Service,
Division of Pulmonary and Critical Care Medicine, NYU School
of Medicine, 550 1st Ave, NBV 7N24, New York, NY 10016;
e-mail: Rany.Condos@nyumc.org
DOI: 10.1378/chest.07-1988
www.chestjournal.org
specialized tuberculosis ward for multidrug-resistant
tuberculosis (MDR-TB) on the Chest Service of Bel-
levue Hospital Center, which is a 768-bed public
hospital in New York City. Seven patients with con-
firmed MDR-TB or XDR-TB who were still culture
positive despite appropriate directly observed ther-
apy were treated with a regimen containing linezolid
and at least one other active agent.
Results: The linezolid-containing regimen led to sus-
tained negative conversion of sputum cultures and
radiographic improvement in all patients. Long-term
therapy (longest duration of therapy, 28 months) was
well tolerated in most patients. Neutropenia devel-
oped in three patients, but was reversible, and pe-
ripheral neuropathy developed in two patients.
Conclusions: Linezolid remains a promising possible
addition to our therapeutic armamentarium against
XDR-TB. Linezolid is associated with side effects
that can be adequately managed. Further studies to
define the mechanism of action and optimum dose
should be performed.
(CHEST 2008; 134:187–192)
Key words: extensively drug-resistant tuberculosis; linezolid
Abbreviations: IFN ⫽ interferon; MDR-TB ⫽ multidrug-resis-
tant tuberculosis; NYCDOH ⫽ New York City Department of
Health; TB ⫽ tuberculosis; XDR-TB ⫽ extensively drug-resis-
tant tuberculosis
T (MDR-TB)
he treatment of multidrug-resistant tuberculosis
is challenging, with an overall response
rate of 56% in 171 patients reported at a specialty
hospital in the pre-HIV era.1 We reported a 65%
response rate in 173 MDR-TB patients who were
treated in the Bellevue Hospital Center Chest Service
from 1983 to 1993.2 At the 60-month follow-up, the
survival rate was 80% in HIV-1–negative patients vs
only 5% in those coinfected with HIV-1. The institution
of appropriate therapy was a positive predictor of
survival and extrapulmonary involvement was a negative
predictor. Cure rates as high as 81% have been report-
ed3 in case series with ofloxacin/levofloxacin-containing
regimens, and a fluoroquinolone agent now is routinely
used in second-line therapy, depending on drug-suscep-
tibility patterns.
The currently available second-line antibiotics that are
used to treat MDR-TB are 4 to 10 times more likely to fail
to elicit a response than the standard therapy for drug-
susceptible tuberculosis (TB) and are about 100 times
more costly.4 New drug development has been hampered
by the enormous resources required for large-scale stud-
ies, the difficulties in evaluating a drug of interest in a
multidrug regimen, and the lack of incentive on the part of
pharmaceutical companies in developing a drug for a
resource-poor population.
Linezolid is an oral antibiotic that is the first to be
approved from the oxazolidinone class with demon-
strated in vitro activity against both drug-susceptible
and drug-resistant isolates of Mycobacterium tubercu-
losis without cross-resistance with the standard antitu-
berculous agents.5 Linezolid reaches microbicidal levels
CHEST / 134 / 1 / JULY, 2008 187