Secondary Logo

Journal Logo

Radiology in ID

Productive Cough With Tinge of Blood and Fever

Adeyemi, Oluwadamilola A. MD*; Grant, Thomas H. DO, FACR; Noskin, Gary A. MD*

Author Information
Infectious Diseases in Clinical Practice: November 2007 - Volume 15 - Issue 6 - p 385-388
doi: 10.1097/ipc.0b013e318159d580
  • Free



A 60-year-old man with asthma was admitted in July 2006 with a 3-day history of cough productive of yellowish, blood-tinged sputum, fever, chills, and drenching sweats. In addition, he noted pleuritic chest wall pain and worsening of his asthma. There were no prior hospitalizations. He had a 25-pack-year smoking history. He occasionally drank alcohol but denied any illicit drug use. He lived alone and was never incarcerated. He initially thought he was having an asthma exacerbation but because his symptoms did not resolve with inhalers, he presented to the emergency department.

On physical examination, he was febrile with a temperature of 102°F, blood pressure of 126/62 mm Hg, heart rate of 112 beats/min, respiratory rate of 20/min, and oxygen saturation on room air was 93%. He had bitemporal wasting and poor dentition, decreased air entry in the left lower lobe, crackles, and diffuse wheezes. The remainder of the physical examination was normal.

His white blood cell count was 22 × 109/L, 90% polymorphonuclear leukocytes, hemoglobin level was 12.1 g/dL, and platelet count was 253 × 109/L. Chemistry was notable for sodium level of 128 mEq/L and creatinine level of 1.7 mg/dL. Human immunodeficiency virus test was negative. His chest radiograph showed consolidation of the superior segments of the left lower lobe (Figs. 1A, B). He was admitted to the hospital and commenced on moxifloxacin for community-acquired pneumonia. He continued to have fever, and on day 2, moxifloxacin was changed to ceftriaxone and azithromycin. On day 3, because of progression of symptoms, a computed tomography (CT) of the chest was ordered and demonstrated a partially cavitary consolidation in the left lower lobe (Figs. 2A-C). He was then placed in respiratory isolation to rule out tuberculosis, and vancomycin was added.

A and B, Posterioanterior and lateral radiographs show a large area of left lower lobe consolidation and peripheral ground glass opacities (black arrow).
A, The CT soft tissue window showing necrosis of the pneumonia. There is a gas collection in the center of the consolidation (white arrow). B and C, Thin-section multidetector CT scan using lung windows demonstrates a large area of left lower lobe consolidation that extends to the pleural surface. Medially, there are also ground-glass opacities and centrilobular nodules.

Blood cultures were negative as were 3 sets of sputum for acid-fast bacilli; however, his sputum culture grew methicillin-resistant Staphylococcus aureus (MRSA). The susceptibility profile was consistent with the community associated MRSA phenotype. Because of a rash due to vancomycin, therapy was changed to linezolid. He improved clinically and symptomatically on linezolid and was discharged home to complete a 21-day course of treatment with follow-up with his primary care physician.


In 1882, Alexander Ogston described staphylococcal disease and its role in sepsis and abscess formation.1 Methicillin-resistant Staphylococcus aureus emerged in the 1960s in the United Kingdom, shortly after the introduction of methicillin and is currently the most commonly identified antibiotic-resistant pathogen in US hospitals.2 Patients with S. aureus infection stay in the hospital longer, incur more charges, and are at increased risk of in-hospital death compared with those without this infection.3 In a recent and dramatic evolutionary development over the last decade, infection with novel community-associated strains of MRSA (CA-MRSA) in previously healthy individuals without either direct or indirect association with health care facilities or typical risk factors has emerged.4-9

The CA-MRSA infection is defined as an illness in which MRSA is cultured from a sterile site of infection in an outpatient setting or less than 48 hours after a hospital admission. These patients should not have been hospitalized, undergone surgery, received dialysis, or resided in a long-term care facility within 1 year before the onset of illness and should not have a permanent indwelling catheter or a previous positive MRSA culture.10 Clusters and outbreaks of CA-MRSA in adolescents and adults have been reported to occur in Native Americans, homeless youths, men who have sex with other men, jail inmates, military recruits, children in child care centers, and competitive athletes.5,7,11-14

The CA-MRSA infection gained widespread attention with the Centers for Disease Control and Prevention report of 4 deaths in North Dakota and Minnesota in 1997-1999 in previously healthy children.15 Two of these children had evidence of necrotizing pneumonia. Most infections caused by CA-MRSA are skin and soft tissue infections, less frequently, severe necrotizing pneumonia, and sepsis, and most recently, rare cases of necrotizing fasciitis have been reported.

An estimated 86.9 million persons in the United States (32.4% of the population) are thought to be colonized (usually in and around the nasal area) with S. aureus. In a study from 2001 to 2002, the estimated prevalence (colonization) of MRSA among S. aureus isolates was approximately 2.5%, for an estimated population carriage of MRSA of 0.84% or 2.2 million persons.16 The true prevalence of CA-MRSA infection remains unknown because it varies by geographic area, and rates of 18.0 cases per 100,000 population in Baltimore and 25.7 cases per 100,000 population in Atlanta were found in a recent study.17


Methicillin resistance is determined by the presence of a penicillin-binding protein with decreased affinity to penicillin.18 The mecA gene encodes this protein and is located on staphylococcal cassette chromosome mec (SCC mec). The CA-MRSA infection in the United States is predominantly caused by the USA 300 clone (although USA 400 clone has also been implicated). The CA-MRSA has been recognized by careful epidemiological evaluation; it is characterized by the presence of a distinct methicillin-resistant staphylococcal cassette chromosome (SCC mec type IV element), susceptibility to multiple antibiotics (other than β lactams), and the presence of Panton-Valentine leukocidin (PVL) genes.8 The PVL, which was described by Panton and Valentine in 1932, belongs to the synergohymenotropic (synergistic protein directed toward cell membranes) class of toxins and is known as a virulence factor for CA-MRSA. It is assembled from 2 components that are secreted separately but combine to create lytic pores in cell membranes of neutrophils.19 The binding of PVL components to neutrophils induces release of the neutrophil chemotactic factors interleukin 8 and leukotriene B4 and a variety of inflammatory mediators before bringing about cell death.20

Francis et al21 reported the first cases of CA-MRSA-associated necrotizing pneumonia by strains carrying PVL gene in healthy adults in the United States. Other fatal cases have been reported in other parts of the world.22-24 Most of the lethal cases of CA-MRSA pneumonia were preceded by influenzalike symptoms.21,24 Hemoptysis was reported in 6 (38%) of 16 patients with strains carrying PVL genes.25 Other reported findings include cough productive of purulent sputum, fever, tachycardia, tachypnea, leukopenia, onset of pleural effusion during hospital stay, septic shock, and general picture of rapidly progressive, hemorrhagic, necrotizing pneumonia requiring mechanical ventilation and vasopressors in the intensive care unit. Agwu et al26 reported florid, watery diarrhea and shock in a 14-year-old adolescent girl with CA-MRSA pneumonia.


The initial imaging procedure of choice should be a chest radiograph. In most cases, the plain film findings may be diagnostic of pneumonia and may eliminate the need for additional radiographic procedures. Computed tomography is used to look for complications in patients not responding to therapy.

The CA-MRSA pneumonia typically causes necrotizing bronchopneumonia. It can be homogeneous or patchy and is commonly seen in the lower lobes. Abscess formation with cavitation is often an early finding. Air bronchograms are rarely present. In children, thin-walled cystic structures called pneumatoceles are usually present. All of the 4 patients described by Francis et al21 had cavitary lesions. A prospective study of staphylococcal lower respiratory tract infection in 31 children showed that radiologically, patchy consolidation was the single most common lesion, followed by pleural effusion with or without pneumothorax.27

Gonzalez et al28 in their report found that 47 (67%) of 70 patients with invasive CA-MRSA infection who underwent pulmonary imaging had abnormal findings. In this report, 14 (29.7%) had empyema, 10 (21.2%) had pneumonia/effusion, 7 (14.8%) had septic emboli, and 4 (8.5%) each had lung abscess, pneumonia with pneumatoceles, diffuse air space disease and/or increased interstitial markings, or atelectasis. Of note, none of the 7 patients with CA-MRSA invasive infection and septic emboli on chest radiography or CT had cardiac vegetations noted on transthoracic echocardiography, although 2 of them had deep venous thrombosis of the lower extremities.

The CT scans have increased sensitivity for radiological findings and may further differentiate patterns on chest radiographs from other etiologies. On thin-section CT, MRSA pneumonia is generally segmental. Areas of consolidation are often associated with smaller centrilobular nodules. Volume loss of the affected lobe is often present. Pleural effusions are seen in most patients; empyemas often complicate the effusions. A spontaneous pneumothorax can occasionally be associated with MRSA pneumonia.


History and physical examination suggestive of severe community-acquired pneumonia in a high prevalence area for CA-MRSA should alert the clinician. Chest radiographs or a chest CT demonstrating lobar consolidation with cavitation (necrotizing pneumonia) is suggestive of MRSA pneumonia. Positive culture of sputum, tracheal aspirate, or bronchoalveolar lavage for MRSA in such setting is diagnostic. In patients with bacteremic pneumonia, positive blood culture for MRSA can also help in diagnosis. The susceptibility pattern of the isolates from pulmonary specimens or blood also helps with differentiating CA-MRSA from the more resistant MRSA that is found in the hospital. Genome sequencing of the MRSA strains to detect SCC mec type genes for several superantigens and toxins like PVL can also be done. In the United States, USA 300 and, less frequently, USA 400 are the dominant clones found. Pulsed field gel electrophoresis can be performed to determine genetic relatedness of isolates for epidemiological purposes.


The most effective therapy for necrotizing pneumonia caused by CA-MRSA has yet to be defined. Currently available agents active against MRSA include vancomycin; however, the growing number of infections caused by CA-MRSA would markedly increase the widespread use of vancomycin therapy that may further promote the development of resistance. The appearance of vancomycin-intermediate S.aureus and, more recently, vancomycin-resistant S. aureus is of concern.

Linezolid was superior to vancomycin in a retrospective subset analysis of 2 prospective, randomized clinical trials probably because of its good intrapulmonary penetration in treating hospital-acquired MRSA pneumonia.29 It also has antitoxin effects; however, it is more costly than other agents and can cause bone marrow suppression. Clindamycin is active against some MRSA isolates and also has an antitoxin effect that warrants its use in necrotizing pneumonia. It is recommended that microbiology laboratories screen for inducible clindamycin resistance in erythromycin-resistant strains, and if found, an alternative antibiotic should be used for treatment. Trimethoprim-sulfamethoxazole has good activity against MRSA in vitro and is well tolerated. Many experts recommend trimethoprim-sulfamethoxazole as therapy for MRSA pneumonia, but further investigation is needed.

Another antibiotic with activity against MRSA is quinupristin/dalfopristin; however, clinical experience in patients with nosocomial MRSA pneumonia is disappointing. In one study, the response rate was only 19.4% compared with 40% in vancomycin-treated patients,30 and use is also limited by its cost and adverse effects.

Daptomycin, an agent with in vitro activity against MRSA, failed in a clinical trial involving patients with pneumonia because it has limited penetration into pulmonary epithelial lining fluid, and its activity is inhibited by pulmonary surfactant.31 No data on MRSA pneumonia are available for tigecycline, a glycyclycline with activity against MRSA.

It has been shown that the action of PVL toxin on neutrophils in vitro may be blocked by specific PVL antibodies found in commercial preparations of intravenous immune globulin.32

In summary, MRSA has emerged as an important organism causing both community-acquired and health care-associated infections. The CA-MRSA generally causes skin and soft tissue infections, but pneumonia occurs as well. The diagnosis is confirmed by culturing respiratory tract secretions and performing standard susceptibility testing. Currently, there is no standard therapy for CA-MRSA pneumonia, but there are multiple different antibiotics that have activity against this organism.


The authors thank Dr Pavani Reddy for her careful review of this manuscript and her constructive feedback.


1. Ogston A. Micrococcus poisoning. J Anat. 1882;17(Pt 1):24-58.
2. Diekema DJ, BootsMiller BJ, Vaughn TE, et al. Antimicrobial resistance trends and outbreak frequency in United States hospitals. Clin Infect Dis. 2004;38(1):78-85.
3. Noskin GA, Rubin RJ, Schentag JJ, et al. The burden of Staphylococcus aureus infections on hospitals in the United States: an analysis of the 2000 and 2001 Nationwide Inpatient Sample Database. Arch Intern Med. 2005;165(15):1756-1761.
4. Salmenlinna S, Lyytikainen O, Vuopio-Varkila J. Community-acquired methicillin-resistant Staphylococcus aureus, Finland. Emerg Infect Dis. 2002;8(6):602-607.
5. Centers for Disease Control and Prevention. Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections-Los Angeles County, California, 2002-2003. MMWR Morb Mortal Wkly Rep. 2003;52(5):88.
6. Herold BC, Immergluck LC, Maranan MC, et al. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA. 1998;279(8):593-598.
7. Centers for Disease Control and Prevention. Methicillin-resistant Staphylococcus aureus infections in correctional facilities-Georgia, California, and Texas, 2001-2003. MMWR Morb Mortal Wkly Rep. 2003;52(41):992-996.
8. Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA. 2003;290(22):2976-2984.
9. Collignon P, Gosbell I, Vickery A, et al. Community-acquired methicillin-resistant Staphylococcus aureus in Australia. Australian Group on Antimicrobial Resistance. Lancet. 1998;352(9122):145-146.
10. Centers for Disease Control and Prevention. Community-associated methicillin-resistant Staphylococcus aureus infections in Pacific Islanders-Hawaii, 2001-2003. MMWR Morb Mortal Wkly Rep. 2004;53(33):767-770.
11. Shahin R, Johnson IL, Jamieson F, et al. Methicillin-resistant Staphylococcus aureus carriage in a child care center following a case of disease. Toronto Child Care Center Study Group. Arch Pediatr Adolesc Med. 1999;153(8):864-868.
12. Groom AV, Wolsey DH, Naimi TS, et al. Community-acquired methicillin-resistant Staphylococcus aureus in a rural American Indian community. JAMA. 2001;286(10):1201-1205.
13. Pan ES, Diep BA, Carleton HA, et al. Increasing prevalence of methicillin-resistant Staphylococcus aureus infection in California jails. Clin Infect Dis. 2003;37(10):1384-1388.
14. Zinderman CE, Conner B, Malakooti MA, et al. Community-acquired methicillin-resistant Staphylococcus aureus among military recruits. Emerg Infect Dis. 2004;10(5):941-944.
15. Centers for Disease Control and Prevention. Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus-Minnesota and North Dakota, 1997-1999. JAMA. 1999;282(12):1123-1125.
16. Mainous AG III, Hueston WJ, Everett CJ, et al. Nasal carriage of Staphylococcus aureus and methicillin-resistant S. aureus in the United States, 2001-2002. Ann Fam Med. 2006;4(2):132-137.
17. Fridkin SK, Hageman JC, Morrison M, et al. Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med. 2005;352(14):1436-1444.
18. Chambers HF, Hartman BJ, Tomasz A. Increased amounts of a novel penicillin-binding protein in a strain of methicillin-resistant Staphylococcus aureus exposed to nafcillin. J Clin Invest. 1985;76(1):325-331.
19. Boussaud V, Parrot A, Mayaud C, et al. Life-threatening hemoptysis in adults with community-acquired pneumonia due to Panton-Valentine leukocidin-secreting Staphylococcus aureus. Intensive Care Med. 2003;29(10):1840-1843.
20. Konig B, Prevost G, Piemont Y, et al. Effects of Staphylococcus aureus leukocidins on inflammatory mediator release from human granulocytes. J Infect Dis. 1995;171(3):607-613.
21. Francis JS, Doherty MC, Lopatin U, et al. Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes. Clin Infect Dis. 2005;40(1):100-107.
22. Dufour P, Gillet Y, Bes M, et al. Community-acquired methicillin-resistant Staphylococcus aureus infections in France: emergence of a single clone that produces Panton-Valentine leukocidin. Clin Infect Dis. 2002;35(7):819-824.
23. Magira EE, Zervakis D, Routsi C, et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: a lethal cause of pneumonia in an adult immunocompetent patient. Scand J Infect Dis. 2007;39(5):466-469.
24. Chua AP, Lee KH. Fatal bacteraemic pneumonia due to community-acquired methicillin-resistant Staphylococcus aureus. Singapore Med J. 2006;47(6):546-548.
25. Gillet Y, Issartel B, Vanhems P, et al. Association between Staphylococcus aureus strains carrying gene for Panton-Valentine leukocidin and highly lethal necrotising pneumonia in young immunocompetent patients. Lancet. 2002;359(9308):753-759.
26. Agwu A, Brady KM, Ross T, et al. Cholera-like diarrhea and shock associated with community-acquired methicillin-resistant Staphylococcus aureus (USA400 clone) pneumonia. Pediatr Infect Dis J. 2007;26(3):271-273.
27. Aderele WI, Osinusi K, Johnson WB, et al. Staphylococcal lower respiratory infection in children. West Afr J Med. 1994;13(1):7-12.
28. Gonzalez BE, Hulten KG, Dishop MK, et al. Pulmonary manifestations in children with invasive community-acquired Staphylococcus aureus infection. Clin Infect Dis. 2005;41(5):583-590.
29. Wunderink RG, Rello J, Cammarata SK, et al. Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Chest. 2003;124(5):1789-1797.
30. Fagon J, Patrick H, Haas DW, et al. Treatment of gram-positive nosocomial pneumonia. Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Nosocomial Pneumonia Group. Am J Respir Crit Care Med. 2000;161(3 Pt 1):753-762.
31. Eisenstein BI. Lipopeptides, focusing on daptomycin, for the treatment of gram-positive infections. Expert Opin Investig Drugs. 2004;13(9):1159-1169.
32. Gauduchon V, Cozon G, Vandenesch F, et al. Neutralization of Staphylococcus aureus Panton Valentine leukocidin by intravenous immunoglobulin in vitro. J Infect Dis. 24;189(2):346-353.
© 2007 Lippincott Williams & Wilkins, Inc.