Official reprint from UpToDate

www.uptodate.com 2016 UpToDate

Overview of pulmonary disease in injection drug users

Author
Jill P Karpel, MD

Section Editor
Talmadge E King, Jr, MD

Deputy Editor
Helen Hollingsworth, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2015. | This topic last updated: May 22, 2015.

INTRODUCTION Injection drug users (IDUs) are at increased risk for acute and chronic pulmonary
complications. These sequelae may be due to pharmacodynamic properties of the drugs, effects of
intravenous contaminants, or complications of the intravenous route of administration.

The general pulmonary complications and drug-specific pulmonary diseases that may result from
injection drug use will be reviewed here. Other complications of injection drug use, such as foreign body
granulomatosis, infective endocarditis, opioid use disorder, cocaine intoxication, and methamphetamine
intoxication, are reviewed separately. (See "Substance use disorder: Principles for recognition and
assessment in general medical care" and "Foreign body granulomatosis" and "Infective endocarditis in
injection drug users" and "Pharmacotherapy for opioid use disorder" and "Acute opioid intoxication in
adults" and "Cocaine: Acute intoxication" and "Methamphetamine intoxication".)

PULMONARY COMPLICATIONS The pulmonary complications associated with intravenous injection

of illicit drugs include pneumonia, septic embolization, noncardiogenic pulmonary edema, foreign body
granulomatosis, emphysema, interstitial lung disease, pulmonary vascular disease, pneumothorax, and
an increased incidence of fatal asthma [1-4].
Pneumonia Injection drug users (IDUs) have a 10-fold increased risk of community-acquired
pneumonia compared with the general population [2]. This may be due to a number of factors:

Concurrent smoking of cigarettes or illicit drugs may impair local lung defenses, macrophage
activity, and mucociliary clearance

The stupor induced by some injected drugs favors development of aspiration pneumonia or lung
abscess (see "Aspiration pneumonia in adults" and "Lung abscess")
Bacteremia may follow injection and may hematogenously infect the lung

HIV-positive IDUs are at substantially higher risk for bacterial pneumonia than HIV-negative IDUs

The organisms that most commonly cause community-acquired pneumonia in this population include
Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae,
and Escherichia coli, although it is difficult to separate out the pathogens associated with HIV-positive
and HIV-negative injection drug use [5,6]. Antimicrobial therapy is initially empiric and based on the
clinical situation, particularly whether the chest radiograph shows focal or diffuse opacities and whether
the patient meets criteria for hospital admission. In patients presenting with typical symptoms of bacterial
pneumonia with focal consolidation on chest radiograph, the initial antibiotic regimen will be directed at
the most common community-acquired pathogens. (See "Diagnostic approach to community-acquired
pneumonia in adults" and "Bacterial pulmonary infections in HIV-infected patients" and "Treatment of
community-acquired pneumonia in adults in the outpatient setting" and "Treatment of communityacquired pneumonia in adults who require hospitalization".)
If the etiology of community-acquired pneumonia is identified using reliable microbiologic methods,
antimicrobial therapy can be focused on that pathogen (table 1). (See "Treatment of communityacquired pneumonia in adults who require hospitalization", section on 'Treatment regimens'.)

For patients who have progressive disease despite antibiotic therapy for bacterial pneumonia, other
considerations include fungal and mycobacterial agents. Candida pneumonia has been reported in IDUs
when the injection drug is contaminated [2].

Tuberculosis (particularly multidrug-resistant tuberculosis) is more prevalent among IDUs than it is in the
general population [7-9]. The excess risk largely relates to covariates which are more frequent among
IDUs, such as poverty, homelessness, malnutrition, HIV infection, and poor medical care. Tuberculosis
should be suspected in patients with a longer prodrome, particularly in the presence of fever or night
sweats for more than a week prior to presentation, or weight loss. In addition, mycobacterial disease
should be suspected in patients with nonresolving pneumonia. (See "Epidemiology of tuberculosis" and
"Clinical manifestations and complications of pulmonary tuberculosis" and "Nonresolving pneumonia",
section on 'Tuberculosis'.)
The use of injection drugs is a strong risk factor for the acquisition of HIV infection. IDUs who present
with pneumonia should be assessed for possible HIV infection. In the presence of known HIV infection,
a variety of opportunistic pulmonary infections in addition to tuberculosis may occur. (See "Approach to
the HIV-infected patient with pulmonary symptoms".)
Septic emboli Septic pulmonary emboli can originate in the peripheral veins at sites of
thrombophlebitis or they can arise from heart valves that have been damaged and infected due to
injection drug use. Right-sided valve (tricuspid) endocarditis is generally found to be more common
among IDUs than left-sided. (See "Pathogenesis of vegetation formation in infective endocarditis" and
"Infective endocarditis in injection drug users", section on 'Clinical evaluation'.)

Patients typically present with fever, but generally do not have an audible murmur or peripheral stigmata
of infective endocarditis. Blood cultures are usually positive. The radiographic manifestations of septic
pulmonary emboli include ill-defined, nodular pulmonary opacities, cavities, abscesses, infarction, and
pulmonary gangrene (image 1). The evaluation and treatment of infective endocarditis in IDUs is
discussed separately. (See "Infective endocarditis in injection drug users".)
Noncardiogenic pulmonary edema Noncardiogenic pulmonary edema (NPE) refers to the
radiographic evidence of alveolar fluid accumulation without hemodynamic evidence to suggest a
cardiogenic etiology and is caused by increased pulmonary capillary permeability. NPE can occur
following intravenous injection of cocaine and, more commonly, opioids [3,10-12]. Acute respiratory
distress syndrome (ARDS) is a more severe form of NPE, associated with severe hypoxemia and the
need for mechanical ventilatory support. (See "Noncardiogenic pulmonary edema" and "Acute
respiratory distress syndrome: Epidemiology, pathophysiology, pathology, and etiology in adults",
section on 'Etiologies and predisposing factors'.)

The exact pathophysiology of NPE due to opioid overdose (eg, heroin or methadone) is unknown, but
may include a direct effect of the drug, cerebral edema (neurogenic), or possibly negative pressure.
Patients with central nervous system depression due to a drug overdose can develop upper airway
obstruction. Breathing against the obstruction can create a strong negative pressure across the alveoli,
which causes pulmonary capillary leakage. (See "Noncardiogenic pulmonary edema", section on 'Opioid
overdose' and "Noncardiogenic pulmonary edema", section on 'Neurogenic pulmonary edema'.)
Patients typically present with decreased mental status and evidence of respiratory insufficiency (eg,
tachypnea, tachycardia, hypoxemia). Patients with NPE due to opiate intoxication typically have severe
respiratory depression requiring naloxone reversal. Co-intoxication with alcohol or cocaine is present in
approximately 50 percent [11]. The majority of these patients are hypoxemic on arrival in the emergency
department [10,11].

Imaging findings in IDUs with NPE were described in a series of 27 patients with opiate-related NPE: 74
percent had bilateral, ground-glass opacities suggestive of pulmonary edema, while unilateral pulmonary
edema or focal opacities were noted in the remainder [10].

The diagnosis of NPE in IDUs is based on the clinical presentation and exclusion of processes in the
differential diagnosis, which includes the other causes of ARDS that may complicate injection drug use,
such as sepsis, pneumonia (bacterial, viral, fungal), aspiration, cardiogenic pulmonary edema, and
pulmonary embolism. (See "Noncardiogenic pulmonary edema".)

For most IDUs with NPE, treatment is supportive. Symptoms and signs typically resolve in 24 hours with
supportive care (eg, supplemental oxygen), although approximately one-third of patients require
mechanical ventilation for 24 to 48 hours. (See "Acute opioid intoxication in adults" and "Noncardiogenic
pulmonary edema", section on 'Treatment'.)
Foreign body granulomatosis Drug users sometimes pulverize tablets intended for oral use,
dissolve them in water, and inject them intravenously. Talc, starch, cotton, and cellulose are used as
filler agents in these tablets and may be carried by the bloodstream until they lodge in the pulmonary
capillary bed; chronic inflammation and multiple foreign body granulomas in the lungs may ensue.

Patients may be asymptomatic or may present with nonspecific complaints such as dyspnea, cough, or
an increase in sputum production. Computed tomography (CT) typically shows diffuse, small nodules (2
to 3 mm) or ground-glass opacities (image 2). Pulmonary hypertension, emphysema, and interstitial
fibrosis can occur if the process is severe. The diagnosis and management of foreign body
granulomatosis are discussed separately. (See "Foreign body granulomatosis".)

Bullous lung disease and emphysema Emphysema and bullous lung disease have been described
in association with HIV infection, but HIV-negative IDUs can also develop these complications,
particularly when methadone, methylphenidate, or talc-containing drugs are injected [13-15]. (See
"Foreign body granulomatosis".)
In one series, the prevalence of bullous lung damage and emphysema among intravenous drug users
(as assessed by chest radiographs) was 2 percent [16]. The bullous cysts were noted predominantly in
the upper lobes and in the lung periphery, with sparing of the central portions of the lungs [16,17]. Other
reports of patients who injected talc-containing drugs have reported a predominance of bullous changes
in the lower lobes [18,19]. Patients present with cough and dyspnea, and usually have combined
obstructive and restrictive defects on pulmonary function testing.

Interstitial lung disease Interstitial lung disease in IDUs is generally associated with foreign body
granulomatosis, but may also be a nonspecific finding due to previous episodes of infection, aspiration,
or infarction. Lymphocytic interstitial pneumonia, a rare interstitial lung disease in the general population,
is seen with increased frequency in HIV-infected individuals. In addition, organizing pneumonia,
sarcoidosis, drug hypersensitivity, and immune reconstitution syndrome can develop in HIV-infected
patients. (See "Foreign body granulomatosis" and "Approach to the adult with interstitial lung disease:
Clinical evaluation" and "Approach to the adult with interstitial lung disease: Diagnostic testing" and
"Approach to the HIV-infected patient with pulmonary symptoms", section on 'Pulmonary diseases and
HIV'.)
Pulmonary hypertension Pulmonary hypertension may be induced by obstruction or obliteration of
the pulmonary vascular bed from multiple causes, including foreign body granulomatosis, emphysema,
or interstitial disease. Patients who are HIV-positive may develop pulmonary arterial hypertension (PAH)
with plexiform lesions and medial hypertrophy. The evaluation and management of pulmonary
hypertension associated with HIV infection is discussed separately. (See "Pulmonary arterial
hypertension associated with human immunodeficiency virus" and "Overview of pulmonary hypertension
in adults".)

Drugs with sympathomimetic properties (eg, cocaine, methamphetamine) can produce transient
pulmonary vasoconstriction. It also appears that chronic use of these drugs can lead to irreversible injury
and production of a syndrome indistinguishable from primary pulmonary hypertension. In one
retrospective study, patients with idiopathic PAH were ten times more likely to use stimulants (ie,
amphetamines, methamphetamines, or cocaine) than patients with PAH due to known risk factors, such

as collagen vascular disease, congenital heart disease, or anorexigen use [20]. (See "Pathogenesis of
pulmonary hypertension", section on 'Drugs and toxins'.)

Pneumothorax and pneumomediastinum Pneumothorax may result from unsuccessful attempts to

inject drugs into the central circulation via the subclavian and jugular veins ("pocket shots"). It has also
been reported as a complication of crack cocaine use, septic pulmonary emboli, and drug-related
bullous disease [21,22]. (See 'Cocaine' below.)
Pneumomediastinum is associated with inhalation of crack cocaine and, less commonly, intranasal
cocaine [23]. It is most likely due to performance of a Valsalva maneuver after inhalation, rather than an
effect of the drug. Approximately 20 percent also had a pneumothorax. (See "Pulmonary complications
of cocaine abuse", section on 'Pneumothorax and pneumomediastinum'.)
Asthma IDUs with asthma appear to have an increased risk of fatal asthma [24-27] (see "Identifying
patients at risk for fatal asthma", section on 'Minor risk factors'):

One toxicologic study of 92 cases of fatal asthma in Chicago found evidence of substance abuse,
most commonly cocaine or opiates, in 32 percent of individuals [24]. It is unclear whether the drugs
themselves or other unidentified factors are responsible for the increased asthma fatalities. Optimal
use of asthma medicines is less frequent among drug users [25], and antiinflammatory medications
were being utilized by just two patients in the Chicago series.
A retrospective review of 152 inner city asthma patients found that intubation and mechanical
ventilation were required more often among patients presenting with an acute exacerbation if they
use cocaine (31 versus 11.5 percent) or heroin (17 versus 2.3 percent), compared with nonusers
[26].

Amyloidosis Bilateral pulmonary nodules containing amyloid (AA) protein have been reported in
IDUs with HIV disease [28]. (See "HIV infection and malignancy: Management considerations", section
on 'Plasma cell disorders'.)
DRUG-SPECIFIC COMPLICATIONS

Cocaine Cocaine is an alkaloid with anesthetic and central nervous system stimulant properties. It
can be inhaled nasally or injected; a heat-stable form produced by boiling with bicarbonate can be
smoked (free-basing). There is a higher incidence of clinically apparent pulmonary complications when
cocaine is smoked versus used intravenously or intranasally. The pulmonary complications associated
with the use of cocaine are multiple and can be divided into acute and chronic pulmonary disorders.
Acute pulmonary complications The acute complications of injection cocaine use overlap with
those of inhaled crack cocaine; the most common are acute pulmonary edema and pulmonary
hemorrhage.

Acute noncardiogenic pulmonary edema (NPE) presents with the rapid onset of dyspnea,
hypoxemia, and diffuse opacities on chest radiograph; altered mental status is frequently also
present in injection drug users (IDUs). Treatment is supportive and includes supplemental
oxygen and ventilator support, if necessary. Clinical improvement generally occurs within 24
to 48 hours. (See 'Noncardiogenic pulmonary edema' above and "Noncardiogenic pulmonary
edema".)
Pulmonary hemorrhage can occur with or without frank hemoptysis and is commonly found
on autopsy in asymptomatic cocaine users [29]. The causes of hemorrhage are probably
multifactorial and may include NPE, pulmonary infarction, infection, and pulmonary
hypertension. Treatment is supportive. (See "Pulmonary complications of cocaine abuse".)
Cardiogenic edema may result from cocaine-induced coronary artery spasm, myocardial
ischemia, and left ventricular dysfunction (image 3). The diagnosis is suspected in patients

with dyspnea, diffuse pulmonary opacities on chest imaging, an elevated brain natriuretic
peptide, and/or reduced left ventricular function by echocardiogram. The diagnosis and
treatment are discussed separately. Of note, beta-adrenergic antagonists (ie, beta-blockers)
are avoided in cocaine-related cardiovascular disease because they may create unopposed
alpha-adrenergic stimulation. (See "Evaluation and management of the cardiovascular
complications of cocaine abuse", section on 'Cardiovascular conditions associated with
cocaine use' and "Cocaine: Acute intoxication", section on 'Cardiovascular complications' and
"Treatment of acute decompensated heart failure: General considerations".)

Pneumothorax and pneumomediastinum are also reported in association with cocaine

inhalation. (See 'Pneumothorax and pneumomediastinum' above.)

Chronic pulmonary complications The chronic pulmonary complications of injection cocaine

use include foreign body granulomatosis, lung scarring due to repeated pulmonary infections and
pulmonary infarction, and pulmonary arterial hypertension (PAH) [30]. (See 'Foreign body
granulomatosis' above and 'Interstitial lung disease' above and 'Pulmonary hypertension' above.)

Opioids Opiates are naturally occurring alkaloids from the poppy plant; the term opioids includes
natural opiates (eg, morphine, codeine) and synthetic derivatives that also bind to opioid receptors in the
brain (eg, heroin, hydrocodone). Use of heroin (diacetyl morphine) is rising in the United States, and
increasingly pure formulations of the drug are available. Most of the direct morbidity and mortality related
to opiate use occur after acute intoxication and are due to anaphylaxis, noncardiogenic pulmonary
edema, acute respiratory acidosis, and aspiration pneumonitis. (See "Acute opioid intoxication in
adults".)
Massive release of histamine from mast cells and basophils may follow narcotic injection due to an
anaphylactoid reaction to the narcotics themselves or to adulterants or contaminants. Shock,
bronchospasm, and upper airway edema may ensue [31]. (See "Anaphylaxis: Rapid recognition
and treatment".)

Heroin-induced noncardiogenic pulmonary edema usually develops rapidly within the first few
hours following injection, but rarely occurs as late as 24 hours. This complication can also occur
with other opiates such as codeine and methadone, as well as fentanyl-heroin mixtures [32].
Oxygen therapy and noninvasive positive pressure ventilation or intubation with mechanical
ventilation may be required. Improvement can occur rapidly, but full resolution generally requires
two to three days. (See 'Noncardiogenic pulmonary edema' above and "Noncardiogenic pulmonary
edema".)
Narcotics powerfully suppress central respiratory drive. Acute administration may produce
hypercapnia, acute respiratory acidosis, and if severe, cardiopulmonary arrest and death.

Narcotics also diminish the level of consciousness and depress the cough reflex. These actions
render narcotic users less able to protect the airway and more likely to develop aspiration
pneumonitis (due to infection or aspirated gastric contents) and lung abscess. Lower lobe
bronchiectasis has been reported among heroin users and may result from prior episodes of
aspiration or pulmonary infection [33]. (See "Aspiration pneumonia in adults" and "Lung abscess".)

In a case report, an intravenous heroin user developed respiratory failure due to organizing
pneumonia; scattered, nonnecrotizing granulomata and multinucleated giant cells with foreign body
particles were also noted [34].

Methylphenidate and methamphetamine Methylphenidate and methamphetamine are

sympathomimetic stimulants that are sometimes injected intravenously by IDUs. General signs and
symptoms of toxicity include restlessness, tachycardia, hypertension, diaphoresis, and confusion. Longterm use of methylphenidate can lead to bullous emphysema.

 Methylphenidate Intravenous methylphenidate has been associated with the development of

hemoptysis, chest pain, and wheezing. One series of 22 patients hospitalized following
methylphenidate use reported that 80 percent had one or more of these findings [35]. Excess
adrenergic activity and vasospasm may underlie these complications.
Habitual intravenous use of methylphenidate has been associated with the development of
panlobar emphysema after one to six years [18,36]. Emphysema primarily involves the lower lobes
of the lungs and has a similar radiographic appearance to alpha-1 antitrypsin deficiency. The
relative contribution of methylphenidate, foreign body granulomatosis, and concomitant smoking in
the genesis of emphysema among these patients is unclear, but one study compared the findings
on chest computed tomography (CT) of patients with foreign body granulomatosis who abused
intravenous methylphenidate with others who did not [37]. A significantly increased prevalence of
lower lobe panacinar emphysema was demonstrated in patients abusing methylphenidate, and
was frequently associated with a fine micronodular pattern and ground-glass attenuation. (See
'Bullous lung disease and emphysema' above.)

Methamphetamine Methamphetamine ("speed" or "crank") is a stimulant drug that has similar

effects to cocaine. It can be smoked or administered intravenously or intranasally. There are rare
case reports of acute noncardiogenic pulmonary edema and pulmonary hypertension following the
inhalation of methamphetamine, but complications of intravenous use are not well documented.
Cardiogenic pulmonary edema can complicate methamphetamine intoxication, possibly related to
fluid resuscitation in the setting of acute hypertension. (See "Methamphetamine intoxication",
section on 'Clinical features' and "Methamphetamine intoxication", section on 'Fluid resuscitation'.)

The evaluation and management of acute methamphetamine intoxication are discussed separately.
(See "Methamphetamine intoxication".)
SUMMARY AND RECOMMENDATIONS

Pulmonary complications associated with intravenous injection of illicit drugs include pneumonia,
septic embolization, foreign body granulomatosis, emphysema, interstitial lung disease, organizing
pneumonia, pulmonary vascular disease, pneumothorax, pneumomediastinum, and an increased
incidence of fatal asthma. (See 'Pulmonary complications' above.)
Injection drug users (IDUs) have a 10-fold increased risk of community-acquired pneumonia
compared with the general population; common causative organisms include Streptococcus
pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae, and
Escherichia coli. In addition, those who develop HIV/AIDS are at risk for opportunistic pulmonary
infections (eg, tuberculosis, atypical mycobacteria, Pneumocystis jirovecii, cytomegalovirus). (See
'Pneumonia' above.)

When tablets intended for oral use are pulverized and injected intravenously, the insoluble agents
in the tablets (eg, talc, cotton, and cellulose) can be trapped in the pulmonary vasculature, migrate
through the vessel walls, and initiate a granulomatous inflammatory response in the perivascular
interstitium. This disease process, known as foreign body granulomatosis, can lead to
development of progressive interstitial lung disease, emphysema, and pulmonary hypertension.
(See 'Foreign body granulomatosis' above and "Foreign body granulomatosis".)

Emphysema and bullous lung disease may result from concomitant cigarette smoking, but are also
associated with HIV infection and intravenous injection of methadone, methylphenidate, and talccontaining drugs. (See 'Pulmonary complications' above.)
Pneumothorax may result from unsuccessful attempts to inject drugs into the central circulation via
the subclavian and jugular veins ("pocket shots"). It has also been reported as a complication of
septic pulmonary emboli and drug-related bullous disease. (See 'Pneumothorax and
pneumomediastinum' above.)

 Complications of intravenous injection of crack cocaine include noncardiogenic and cardiogenic

pulmonary edema, acute and recurrent alveolar hemorrhage, and interstitial lung disease due to
foreign body granulomatosis. (See 'Cocaine' above.)
Pulmonary complications related to opioid injection typically occur in the setting of acute
intoxication and are due to anaphylaxis, noncardiogenic pulmonary edema, hypoventilation with
acute respiratory acidosis, and aspiration pneumonitis. (See 'Opioids' above and "Acute opioid
intoxication in adults" and "Opioid intoxication in children and adolescents".)

Intravenous injection of methylphenidate has been associated with hemoptysis, chest pain, and
wheezing; excess adrenergic activity and vasospasm may underlie these complications. Foreign
body granulomatosis and emphysema are complications associated with long-term use.
Methamphetamine ("speed" or "crank") is a stimulant drug that has similar effects to cocaine and is
rarely associated with noncardiogenic pulmonary edema and pulmonary hypertension. (See
'Methylphenidate and methamphetamine' above.)
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REFERENCES
1. Hind CR. Pulmonary complications of intravenous drug misuse. 1. Epidemiology and non-infective
complications. Thorax 1990; 45:891.
2. Hind CR. Pulmonary complications of intravenous drug misuse. 2. Infective and HIV related
complications. Thorax 1990; 45:957.

3. Todorovi MS, Mitrovi S, Aleksandri B, et al. Association of pulmonary histopathological findings

with toxicological findings in forensic autopsies of illicit drug users. Vojnosanit Pregl 2011; 68:639.
4. Passarino G, Ciccone G, Siragusa R, et al. Histopathological findings in 851 autopsies of drug
addicts, with toxicologic and virologic correlations. Am J Forensic Med Pathol 2005; 26:106.

5. Caiaffa WT, Vlahov D, Graham NM, et al. Drug smoking, Pneumocystis carinii pneumonia, and
immunosuppression increase risk of bacterial pneumonia in human immunodeficiency virusseropositive injection drug users. Am J Respir Crit Care Med 1994; 150:1493.

6. Madeddu G, Porqueddu EM, Cambosu F, et al. Bacterial community acquired pneumonia in HIVinfected inpatients in the highly active antiretroviral therapy era. Infection 2008; 36:231.

7. Reichman LB, Felton CP, Edsall JR. Drug dependence, a possible new risk factor for tuberculosis
disease. Arch Intern Med 1979; 139:337.
8. Frieden TR, Sterling T, Pablos-Mendez A, et al. The emergence of drug-resistant tuberculosis in
New York City. N Engl J Med 1993; 328:521.
9. Perlman DC, Salomon N, Perkins MP, et al. Tuberculosis in drug users. Clin Infect Dis 1995;
21:1253.

10. Sporer KA, Dorn E. Heroin-related noncardiogenic pulmonary edema : a case series. Chest 2001;
120:1628.
11. Sterrett C, Brownfield J, Korn CS, et al. Patterns of presentation in heroin overdose resulting in
pulmonary edema. Am J Emerg Med 2003; 21:32.

12. Kissner DG, Lawrence WD, Selis JE, Flint A. Crack lung: pulmonary disease caused by cocaine
abuse. Am Rev Respir Dis 1987; 136:1250.

13. O'Donnell AE, Pappas LS. Pulmonary complications of intravenous drug abuse. Experience at an
inner-city hospital. Chest 1988; 94:251.
14. Par JP, Cote G, Fraser RS. Long-term follow-up of drug abusers with intravenous talcosis. Am
Rev Respir Dis 1989; 139:233.

15. Stern EJ, Frank MS, Schmutz JF, et al. Panlobular pulmonary emphysema caused by i.v. injection
of methylphenidate (Ritalin): findings on chest radiographs and CT scans. AJR Am J Roentgenol
1994; 162:555.

16. Goldstein DS, Karpel JP, Appel D, Williams MH Jr. Bullous pulmonary damage in users of
intravenous drugs. Chest 1986; 89:266.

17. Gurney JW, Bates FT. Pulmonary cystic disease: comparison of Pneumocystis carinii
pneumatoceles and bullous emphysema due to intravenous drug abuse. Radiology 1989; 173:27.
18. Shlomi D, Shitrit D, Bendayan D, et al. Successful lung transplantation for talcosis secondary to
intravenous abuse of oral drug. Int J Chron Obstruct Pulmon Dis 2008; 3:327.

19. Marchiori E, Loureno S, Gasparetto TD, et al. Pulmonary talcosis: imaging findings. Lung 2010;
188:165.

20. Chin KM, Channick RN, Rubin LJ. Is methamphetamine use associated with idiopathic pulmonary
arterial hypertension? Chest 2006; 130:1657.

21. Aguado JM, Arjona R, Ugarte P. Septic pulmonary emboli. A rare cause of bilateral pneumothorax
in drug abusers. Chest 1990; 98:1302.
22. Fiorelli A, Accardo M, Rossi F, Santini M. Spontaneous pneumothorax associated with talc
pulmonary granulomatosis after cocaine inhalation. Gen Thorac Cardiovasc Surg 2014.
23. Alnas M, Altayeh A, Zaman M. Clinical course and outcome of cocaine-induced
pneumomediastinum. Am J Med Sci 2010; 339:65.

24. Levenson T, Greenberger PA, Donoghue ER, Lifschultz BD. Asthma deaths confounded by
substance abuse. An assessment of fatal asthma. Chest 1996; 110:604.

25. National Asthma Education and Prevention Program: Expert panel report III: Guidelines for the
diagnosis and management of asthma. Bethesda, MD: National Heart, Lung, and Blood Institute,
2007. (NIH publication no. 08-4051). www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm
(Accessed on February 28, 2011).
26. Levine M, Iliescu ME, Margellos-Anast H, et al. The effects of cocaine and heroin use on
intubation rates and hospital utilization in patients with acute asthma exacerbations. Chest 2005;
128:1951.
27. Doshi V, Shenoy S, Ganesh A, et al. Profile of Acute Asthma Exacerbation in Drug Users. Am J
Ther 2014.
28. Shah SP, Khine M, Anigbogu J, Miller A. Nodular amyloidosis of the lung from intravenous drug
abuse: an uncommon cause of multiple pulmonary nodules. South Med J 1998; 91:402.
29. Bailey ME, Fraire AE, Greenberg SD, et al. Pulmonary histopathology in cocaine abusers. Hum
Pathol 1994; 25:203.

30. Yakel DL Jr, Eisenberg MJ. Pulmonary artery hypertension in chronic intravenous cocaine users.
Am Heart J 1995; 130:398.
31. Edston E, van Hage-Hamsten M. Anaphylactoid shock--a common cause of death in heroin
addicts? Allergy 1997; 52:950.

32. Algren DA, Monteilh CP, Punja M, et al. Fentanyl-associated fatalities among illicit drug users in
Wayne County, Michigan (July 2005-May 2006). J Med Toxicol 2013; 9:106.

33. Banner AS, Rodriguez J, Sunderrajan EV, et al. Bronchiectasis: a cause of pulmonary symptoms
in heroin addicts. Respiration 1979; 37:232.
34. Bishay A, Amchentsev A, Saleh A, et al. A hitherto unreported pulmonary complication in an IV
heroin user. Chest 2008; 133:549.

35. Parran TV Jr, Jasinski DR. Intravenous methylphenidate abuse. Prototype for prescription drug
abuse. Arch Intern Med 1991; 151:781.
36. Sherman CB, Hudson LD, Pierson DJ. Severe precocious emphysema in intravenous
methylphenidate (Ritalin) abusers. Chest 1987; 92:1085.

37. Ward S, Heyneman LE, Reittner P, et al. Talcosis associated with IV abuse of oral medications:
CT findings. AJR Am J Roentgenol 2000; 174:789.
Topic 4337 Version 7.0

GRAPHICS

Recommended antimicrobial therapy for specific pathogens

causing community-acquired pneumonia in adults
Organism
Streptococcus pneumoniae

Penicillin nonresistant; MIC

<2 microgram/mL

Preferred
antimicrobial(s)
Penicillin G, amoxicillin

Alternative
antimicrobial(s)
Macrolide, cephalosporins (oral
[cefpodoxime, cefprozil,
cefuroxime, cefdinir,

cefditoren] or parenteral

[cefuroxime, ceftriaxone,
cefotaxime]), clindamycin,

Penicillin resistant; MIC 2

microgram/mL

Haemophilus influenzae
Non-beta-lactamase
producing

Beta-lactamase producing

Agents chosen on the basis of

susceptibility, including
cefotaxime, ceftriaxone,
fluoroquinolone
Amoxicillin
Second- or third-generation
cephalosporin, amoxicillinclavulanate

doxycyline, respiratory
fluoroquinolone*

Vancomycin, linezolid, highdose amoxicillin (3 g/day with

penicillin MIC 4
microgram/mL)

Fluoroquinolone, doxycycline,
azithromycin, clarithromycin
Fluoroquinolone, doxycycline,
azithromycin, clarithromycin

Mycoplasma
pneumoniae/Chlamydophila
pneumoniae

Macrolide, a tetracycline

Fluoroquinolone

Doxycyline

Chlamydophila psittaci

Fluoroquinolone,
azithromycin
A tetracycline
A tetracycline

Macrolide

Doxycycline

Macrolide

Gentamicin, streptomycin

Legionella species

Coxiella burnetii

Francisella tularensis
Yersinia pestis

Bacillus anthracis
(inhalation)

Enterobacteriaceae

Pseudomonas aeruginosa

Streptomycin, gentamicin

Ciprofloxacin, levofloxacin,
doxycycline (usually with
second agent)
Third-generation
cephalosporin,
carbapenem (drug of
choice if extended-spectrum
beta-lactamase producer)
Antipseudomonal betalactam plus (ciprofloxacin
or levofloxacin or
aminoglycoside)

Doxycyline, fluoroquinolone
Other fluoroquinolones;
beta-lactam, if susceptible;
rifampin; clindamycin;
chloramphenicol

Beta-lactam/beta-lactamase
inhibitor , fluoroquinolone

Aminoglycoside plus
(ciprofloxacin or
levofloxacin )

Burkholderia pseudomallei
Acinetobacter species

Staphylococcus aureus
Methicillin susceptible

Carbapenem, ceftazidime
Carbapenem

Fluoroquinolone, TMP-SMX
Cephalosporin-

aminoglycoside, ampicillinsulbactam, colistin

Antistaphylococcal penicillin

Cefazolin, clindamycin

Bordetella pertussis

Macrolide

TMP-SMX

Influenza virus

Refer to associated topic

reviews

Methicillin resistant

Anaerobe (aspiration)

Mycobacterium tuberculosis

Coccidioides species

Histoplasmosis
Blastomycosis

Vancomycin or linezolid

Beta-lactam/beta-lactamase
inhibitor , clindamycin

TMP-SMX

Carbapenem

Isoniazid plus rifampin plus

ethambutol plus
pyrazinamide

Depends on susceptibility
pattern. Refer to associated
topic reviews.

Itraconazole**

Amphotericin B**

For uncomplicated infection

in a normal host, no
therapy generally
recommended; for therapy,
itraconazole, fluconazole.
Itraconazole**

Amphotericin B

Amphotericin B**

Choices should be modified on the basis of susceptibility test results and advice from local
specialists. Refer to local references for appropriate doses.
Preferred agent may change over time due to changing resistance patterns and depends
on many factors, including severity of illness. Refer to associated topic reviews for
updated and detailed treatment recommendations for each pathogen.

MIC: minimum inhibitory concentration; ATS: American Thoracic Society; CDC: Centers for
Disease Control and Prevention; IDSA: Infectious Diseases Society of America; TMP-SMX:
trimethoprim-sulfamethoxazole.
* Levofloxacin, moxifloxacin, gemifloxacin (not a first-line choice for penicillin susceptible
strains); ciprofloxacin is appropriate for Legionella and most gram-negative bacilli (including H.
influenzae).
Azithromycin is more active in vitro than clarithromycin for H. influenzae.
Imipenem-cilastatin, meropenem, ertapenem.
Piperacillin-tazobactam for gram-negative bacilli, ticarcillin-clavulanate, ampicillin-sulbactam,
or amoxicillin-clavulanate.
Ticarcillin, piperacillin, ceftazidime, cefepime, aztreonam, imipenem, meropenem.
750 mg daily.
Nafcillin, oxacillin, flucloxacillin.
Choice of antiviral regimen depends on type of influenza virus and expected resistance
pattern. (Refer to the UpToDate topic on antiviral drugs for the treatment of influenza in
adults.)
** Preferred agent depends on severity of illness. Refer to associated topic reviews for full
discussions.

Adapted with permission from: Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases
Society of America/American Thorac Society Consensus Guidelines on the Management of

Community-acquired Pneumonia in Adults. Clin Infect Dis 2007; 44:S27. Copyright 2007
University of Chicago Press.
Graphic 64816 Version 8.0

Septic embolization in an intravenous drug user

with tricuspid valve endocarditis

Chest radiograph shows multiple ill-defined nodular opacities, some with

cavitation. This is an example of multifocal patchy opacification.
Courtesy of Paul Stark, MD.
Graphic 59037 Version 4.0

Talc granulomatosis

Talc granulomatosis in an intravenous drug user with multiple, partially

confluent, bilateral micronodules.
Courtesy of Paul Stark, MD.
Graphic 53000 Version 3.0

Hydrostatic pulmonary edema

Pulmonary edema in a "butterfly distribution" due to left ventricular

failure. Chest radiograph shows large perihilar opacities in patient with

enlarged cardiac silhouette.
Courtesy of Paul Stark, MD.
Graphic 58394 Version 4.0

Disclosures

Disclosures: Jill P Karpel, MD Nothing to disclose. Talmadge E King, Jr, MD Consultant/Advisory Boards: InterMune
[pulmonary fibrosis (pirfenidone)]; ImmuneWorks [pulmonary fibrosis]; Boehringer Ingelheim [IPF (nintedanib)]; GlaxoSmithKline
[pulmonary fibrosis]; Daiichi Sankyo [pulmonary fibrosis]. Helen Hollingsworth, MD Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting
through a multi-level review process, and through requirements for references to be provided to support the content.
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