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Post-viral influenza Streptococcus pneumoniae pneumonia in an intravenous drug abuser
Post-viral influenza Streptococcus pneumoniae pneumonia in an intravenous drug abuser Sowjanya S. Mohan, MD, Vinay Nair, DO, and Burke A. Cunha, MD, Mineola and Stoney Brook, New York
Viral influenza is a seasonal cause of community-acquired pneumonia (CAP). Viral influenza may be caused by influenza A or B and affect any age group. Viral influenza A is usually more severe than influenza B in adults. Viral influenza may present as 3 clinical scenarios: viral influenza alone, viral influenza followed in 1 to 3 days by Staphylococcus aureus pneumonia, or viral influenza followed in 1 to 3 weeks by pneumonia caused by Streptococcus pneumoniae or Haemophilus influenzae. Intravenous drug abusers (IVDAs) are predisposed to a variety of infectious diseases but are not particularly predisposed to viral influenza. We present a case of a young IVDA who presented with influenza A pneumonia who subsequently developed S. pneumoniae CAP. The pneumonococcal suprainfection was severe and prolonged and characterized by a small cavity, empyema, pneumatoceles, and bronchopleural fistulae. S. pneumoniae pleural effusions are uncommon, but pleural empyemas are often demonstrated. Tracheobronchial fistulae and cavitation are rare complications of S. pneumoniae CAP in adults. To the best of our knowledge, this is the first case of post-viral influenza pneumococcal pneumonia in an IVDA. (Heart Lung® 2005;34:222– 6.)
V
iral influenza may be caused by influenza type A or B. Influenza B is more common in children and is usually a milder disease than influenza A. Influenza occurs as outbreaks usually during the winter months, and most often the influenza season peaks in February. The onset of influenza is acute and is accompanied by fever, headaches, myalgias, and severe malaise. Patients often can recall the exact hour that the influenza has affected them. The pneumonia accompanying influenza is a variable severity. The clinical spectrum of viral influenza pneumonia runs from minimal shortness of breath to severe hypoxemia and death. The influenza virus depresses local lung host defenses and predisposes to subsequent bacterial invasion. Patients with influenza pneumonia may present with 1 of 3 distinct clinical scenarios. The first scenario is that of a solitary entity with fever, headaches, myalgias, substernal chest pain, and intercostal muscle involvement mimicking pleuritic From the Infectious Disease Division, Winthrop-University Hospital, Mineola, New York, and State University of New York School of Medicine, Stony Brook, New York. Address for reprints: Burke A. Cunha, MD, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501. 0147-9563/$ – see front matter Copyright © 2005 by Mosby Inc. doi:10.1016/j.hrtlng.2004.07.006
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chest pain. The cough is dry and nonproductive. On physical examination, the lungs are silent and the chest radiograph reveals no infiltrates or diffuse bilateral symmetrical haziness. The white blood cell count is either normal or decreased. The second clinical scenario is that of influenza followed 2 to 3 days later by superimposed Staphylococcus aureus bacterial pneumonia. In contrast with patients with only viral influenza pneumonia, these patients have a productive cough and become critically ill within 2 to 3 days. Such patients have central cyanosis and severe hypoxemia. Chest radiograph reveals multiple focal segmental infiltrates with cavitation. Pneumatoceles are common in children, and pneumothoraces or abscesses are common in adults. The patients with this second clinical scenario are the most critically ill and have the highest mortality and morbidity rate. The third clinical scenario is that of influenza that may be followed 1 to 3 weeks after the initial presentation with late bacterial pneumonia. These patients have an interval after their illness of relative stability without clinical deterioration. The late onset of bacterial pneumonia is heralded by a productive cough and recurrence of fever. Such patients are not usually critically ill; they present with community-acquired pneumonia (CAP) and have focal, seg-
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Post-viral influenza Streptococcus pneumoniae pneumonia in an IVDA
Fig 1 Fever pattern and white blood cell count during hospitalization.
mental, or lobar infiltrates without cavitation. The usual organisms causing late bacterial pneumonia after influenza are H. influenzae and S. pneumoniae. Cavitation is not a feature of either S. pneumoniae or H. influenzae CAP. Prognosis is good with appropriate and early antimicrobial therapy.1-6 Pneumococcal CAP usually presents with high fever, rigors, productive cough, and pleuritic chest pain. Radiographic features typically reveal 1 or more segmental or lobar infiltrates. Pleural effusions are uncommon. Diagnosis is suggested by sputum Gram stain or culture. Blood culture results are often positive. Blood culture positivity may be higher in patients with lobar consolidation or air bronchograms. Necrotizing S. pneumoniae is extremely rare.7-10 We report a case of a young male intravenous drug abuser (IVDA) who presented with viral influenza A complicated by late pneumococcal pneumonia with empyema and bronchopleural fistulae.
ILLUSTRATIVE CASE A 25-year-old man presented to the emergency department with a history of fever, malaise, severe myalgias, and shortness of breath for 3 days. The patient was well until 3 days before admission when he began having fevers and malaise. He was seen by his primary care physician, who prescribed oseltamivir for presumed viral influenza, but his symptoms progressed. He developed shortness of breath and a nonproductive dry cough. His fever, myalgias, and shortness of breath continued to worsen until the day of admission. The patient had mild asthma, and he occasionally smoked tobacco and marijuana. He also drank alcohol and was an IVDA of heroin.
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On physical examination, he was afebrile with a blood pressure of 89/54 mm Hg, heart rate of 130 beats/min, and oxygen saturation of 59% on room air. Physical examination revealed tachycardia and bronchial breath sounds with egophony over the entire right lung. His abdomen was soft with mild tenderness diffusely. Laboratory data showed a white blood cell count of 2,300 cells/mm3 (43% bands, 45% neutrophils, 9% lymphocytes, and 3% metamyelocytes). The platelet count was 168,000 K/mm3. Renal function was impaired with blood urea nitrogen of 76 mg/dL and creatinine of 6.3 mg/dL. Liver enzymes were slightly elevated, and erythrocyte sedimentation rate was 114 mm/h (N ⫽ 1-16). A chest radiograph showed right lung consolidation with infiltrates in the left middle and lower lung fields as well as a right pleural effusion. Computed tomography scan of the chest without contrast showed consolidation of the right lung with a left lung infiltrate. An arterial blood gas revealed pH: 7.37 mm Hg, PCO2: 47 mm Hg, PO2: 59.8 mm Hg, and oxygen saturation of 80% on a 100% O2 non-rebreather mask (Fig 1). The patient was intubated, started on pressors for blood pressure support, and given 1 dose of moxifloxacin 400 mg intravenously (IV). He was then transferred to the intensive care unit where he was started on amantadine 100 mg (by mouth) every 12 hours for influenza, cefepime 2 g (IV) every 12 hours, and doxycycline 100 mg (IV) every 12 hours for CAP coverage. A bronchoscopy was performed, and bronchial washings and bronchial lavage were obtained. Bronchial washing and lavage cultures also grew Streptococcus pneumoniae. Blood cultures taken on admission were positive for Streptococcus pneu-
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moniae. Urine pneumococcal antigen test showed negative results. The patient was switched to ceftriaxone 2 g (IV) every 24 hours. On the fourth day, the chest radiograph showed a small developing lucency in the right middle lung. A second computed tomography scan of the chest showed a pneumomediastinum and confluent pneumatoceles in the right middle lung, consistent with cavitary pneumonia. There was an increase in the right pleural empyema and a decrease in the right middle lobe and right lower lobe infiltrates; the left lung showed a progression of infiltrates. The patient’s hospital course was further complicated by a right lung pneumothorax on the fifth day of admission, which was treated with chest tube placement. He also had a right-sided loculated pleural empyema and multiple right bronchopleural fistulae despite continued fevers. The patient began to improve clinically and was extubated on the 19th day of admission. The patient became afebrile on the 23rd hospital day and was discharged on the 32nd day with moxifloxacin 400 mg (by mouth) every 24 hours for an additional 2 weeks. Serologic tests for Epstein-Barr virus; cytomegalovirus; hepatitis A, B, and C viruses; Leptospira; chlamydia; Legionella; mycoplasma; group A streptococcus; and human immunodeficiency virus showed negative results. Initial influenza A antibody titers, negative at the time of admission, became positive (1:16) after 2 weeks. Bronchial washings and blood cultures were positive for S. pneumoniae, but urinary antigen test for S. pneumoniae showed negative results.
DISCUSSION Severe pneumococcal infections occur in patients with asplenia, functional asplenia, and abnormal immunoglobulins such as multiple myeloma, human immunodeficiency virus, and lymphoma. Even in these settings, necrotizing pneumococcal pneumonia is rare because Streptococcus pneumoniae does not produce necrotoxins. Microabscesses are not typical and should raise suspicion of an anatomic abnormality.7,8 Viral influenza pneumonia, particularly viral influenza, may, when severe, be fatal or become complicated by subsequent bacterial superinfection. The onset of viral influenza is sudden and characterized by fever, headache, severe myalgias, and profound malaise. Rhinorrhea, sore throat, and conjunctival suffusion are often present early in the clinical course. Physical examination of the lungs
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reveals no adventitious sounds. The lungs are quiet because viral influenza is an interstitial process that causes an oxygen diffusion defect across the alveolar membrane. Therefore, auscultation does not reveal any sound emanating from the alveoli, which are uninvolved viral influenza. Similarly, the chest radiograph looks deceptively normal or near normal even in very sick individuals. If infiltrates are present at all, they are bilateral, symmetric, perihilar, and interstitial in nature and are barely discernible as minimal diffuse haziness. In severe viral influenza that has progressed, bilateral fluffy infiltrates may develop. Viral influenza affects the respiratory epithelium and decreases local pulmonary host defense mechanisms. The denuded of a respiratory epithelium predisposes to subsequent bacterial invasion. The second clinical presentation of viral influenza pneumonia is that complicated by bacterial super infections that occur 2 to 3 days after the initial presentation of influenza. S. aureus is the most common pathogen responsible for early bacterial infection post-viral influenza pneumonia. Staphylococcal pneumonia is characterized by multiple focal segmental or lobar infiltrates that cavitate within 72 hours. These patients are critically ill and have high fever, are cyanotic, and have a productive cough. The sputum in such patients contains S. aureus, which may be demonstrated by Gram stain or culture. In contrast with viral influenza, in which a normal white blood cell count or leukopenia is the rule, early bacterial super infection post-viral influenza is characterized by a marked leukocytosis. Only 2 organisms can cause rapid cavitation in 72 hours or less, that is, S. aureus and P. aeruginosa. Because P. aeruginosa is not a pathogen that is associated with viral influenza, pneumonia occurring 2 to 3 days after viral influenza accompanied by cyanosis or rapid cavitation should be considered attributable to S. aureus until proven otherwise. The other clinical presentation viral influenza pneumonia is that of late bacterial suprainfection. Patients who present with influenza pneumonia improve somewhat after the initial presentation, but after 1 to 3 weeks, they suddenly develop fever and a productive cough accompanied by leukocytosis. Chest radiograph reveals focal or segmental lobar infiltrates without cavitation. These patients are less critically ill than those with Staphylococcal post-influenza pneumonia. The sputum reveals either pleomorphic gram-negative aerobic bacilli (eg, H. influenzae) or gram-positive diplococci (eg, S. pneumoniae). Because both S. pneumoniae and H. influenzae are bacteremic organisms, blood cultures are frequently positive in CAP caused by either of
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Post-viral influenza Streptococcus pneumoniae pneumonia in an IVDA
Mohan, Nair, and Cunha
Table I Clinical presentations of viral influenza pneumonia
Usual pathogens
Viral Influenza
Influenza followed by early bacterial pneumonia
Influenza followed by late bacterial pneumonia
Influenza virus
Influenza followed by Staphylococcus aureus
Influenza followed by S. pneumoniae or Haemophilus influenzae
Delay after initial None presentation Symptoms Nonproductive dry cough, severe prostration, restlessness, sore throat, headache, myalgias, substernal chest pain, intercostal myalgias, mimicking pleuritic chest pain Signs Conjunctival injection, non-exudative pharyngitis, no rales, hypoxemia, normal breath sounds WBC count Normal/decreased Chest film Normal, no focal/segmental infiltrates, diffuse haziness
2–3 days after clinical presentation Productive cough, sudden deterioration after 2–3 days, critically ill
1–3 weeks after clinical presentation Productive cough, with or without pleuritic chest pain, not critically ill
Central cyanosis, hypotension diffuse rales, severe hypoxemia
Fever recurs after becoming afebrile, localized rales, with or without decreased breath sounds Leukocytosis Lobar consolidation, no cavitation
Marked leukocytes Multiple focal/segmental infiltrates, rapid cavitation, pneumatoceles (children), pneumothorax, multiple abscesses
WBC, White blood cell. Adapted from Cunha BA, Qadir MT. Viral influenza. Infect Disease Pract 1996;20:13.
these pathogens. Bacteremia is part of the pathophysiology of both H. influenzae and S. pneumoniae CAP and should not be viewed as a complication or bad prognostic sign per se. Patients with S. pneumoniae postviral influenza pneumonia are usually less ill and have a less difficult course than those with S. aureus early bacterial pneumonia after viral influenza.5,6,11-15 Our patient was an IVDA and had an unusually severe and protracted course of febrile illness. There are several lessons to be learned from the illustrative case presented. The first lesson is that IVDAs are predisposed to certain infections but may be infected with the same organisms that affect normal hosts, for example, viral influenza. Clinicians should remember that viral influenza might present as 3 distinct clinical scenarios. This case illustrates
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that there is an important difference between early bacterial pneumonia post-viral influenza caused by S. aureus and late bacterial pneumonia post-viral influenza caused by S. pneumoniae or H. influenzae. These differences are described in this article and shown in Table I. Another important point is that S. pneumoniae CAP infrequently is associated with pleural effusion in contrast with what is usually cited in the literature but frequently is complicated by empyema. Cavitation is not a feature of S. pneumoniae CAP. Cavitary S. pneumoniae is exceedingly rare in the literature and occurs most often in children. In adults, “cavitary pneumococcal pneumonia” should be considered attributable to Klebsiella pneumoniae until proven otherwise. K. pneumoniae characteristically cavitates after 3 to 5 days in patients with
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Klebsiella CAP. On the rare occasions in which S. pneumoniae does cause cavitation, it usually occurs in children after 3 to 5 days as well. The extreme rarity of cavitation in S. pneumoniae CAP is because S. pneumoniae does not elaborate necrotoxins that are responsible for cavitary lung lesions. In terms of serologic tests at presentation, titers are often negative because the host defenses have not had an adequate time to develop an immune response. In this case, the initial influenza A titers were negative, but 2 weeks later they were elevated at 1:16. The patient was lost to follow-up, and subsequent titers were not available. Urinary antigen tests for various bacteria, Legionella, S. pneumoniae, Escherichia coli, and so forth, are useful if no other diagnostic modality is positive. A negative urinary antigen test result for bacterial pathogens does not rule out infection. The main problem with the urinary antigen test is that it frequently shows negative results initially until sufficient antigen urea occurs to make the test result positive. Positive antigen urea persists for weeks or months, which is the main advantage of urinary antigen diagnostic tests. However, in this case the urinary antigen test result never became positive during the weeks of hospitalization of the patient. Fortunately, the diagnosis was confirmed by bronchial washings, which were positive for S. pneumoniae. Last, our patient had a penicillin-sensitive strain of S. pneumoniae, for example, minimum inhibitory concentration of 0.1 mg/mL or less, and was treated successfully with a variety of antibiotics. Except for highly resistant strains of S. pneumoniae, pneumococci at a minimum inhibitory concentration of 0.8 mg/mL or less still responds to adequately dosed penicillin or beta lactam antibiotics. Our patient was treated with a variety of antibiotics with a high degree of anti-S. pneumoniae activity, and therapy was completed with oral moxifloxacin therapy. Last, the clinical lesson from this case is that although late bacterial pneumonia post-viral influenza is usually less severe than S. aureus, this case indicates that infection with S. pneumoniae may be severe, complicated, and prolonged as in the case of this young IVDA. S. pneumoniae CAP alone or after viral influenza is frequently accompanied by bacteremia, which is
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part of the natural disease process and is not per se a bad prognostic indicator. Another point of interest is the fact that although the patient had blood culture results at admission that were positive for S. pneumoniae, a urinary antigen assay (ie, an enzyme immunoassay test [counterimmunoelectrophoresis]), performed over the course of the admission, had repeatedly negative results. This test has a reported sensitivity and specificity of 93% and 79%, respectively. Our case demonstrates that urinary antigen tests should not be used as a sole method of diagnosis.
REFERENCES 1. Christie AB. Influenza. In: Infectious diseases: epidemiology and clinical practice. New York: Churchill Livingston; 1964. pp. 222-6. 2. Crosby AW. Influenz. In: Kiple KF, editor. The Cambridge world history of human disease. New York: Cambridge University Press; 1993. pp. 807-11. 3. Kilbourne ED, editor. The influenza viruses and influenza. Orlando: Academic Press; 1995. 4. Douglas RG. Jr. Influenza in man. In: Kilbourne ED, editor. The influenza viruses and influenza. Orlando: Academic Press; 1975. pp. 347-395. 5. Louria DB, Blumenfield HL, Ellis JT. Studies on influenza in the pandemic of 1957-1958. II Pulmonary complications of influenza. J Clin Invest 1959;38:213-65. 6. Petersdorf RG, Fusco JJ, Harter DH, et al. Pulmonary infections complicating Asian influenza. Arch Intern Med 1959;103: 262-72. 7. Ort S, Ryan RL, Barden G, et al. Pneumococcal pneumonia in hospitalized patients. JAMA 1983;249:214-8. 8. Watanakunakorn C, Bailey TA. Adult bacteremic pneumococcal pneumonia in a community teaching hospital, 1992-1996. A detailed analysis of 108 cases. Arch Intern Med 1997;157: 1965-71. 9. Yangco BG, Deresinski SC. Necrotizing or cavitating pneumonia due to Streptococcus pneumoniae: report of four cases and review of literature. Medicine 1980;59:449-57. 10. Musher DM, Alexandraki I, Graviss EA, et al. Bacteremia and nonbacteremic pneumococcal pneumonia. A prospective study. Medicine 2000;79:210-21. 11. Heffelfinger JD, Dowell SF, Jorgensen JH, et al. Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group. Arch Intern Med 2001;260:1399-1408. 12. Cunha BA, Qadir MT. Viral influenza. Infect Dis Pract 1996;20:13. 13. Cunha BA. Viral influenza and its complications. Emerg Med 2000;32:56-67. 14. Cunha BA: Severe community-acquired pneumonia. J Crit Illness 1997;12:711-21. 15. Cunha BA. Antibiotic treatment of severe community pneumonia. Semin Respir Crit Care Med 2000;21:61-9.
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Viral influenza is a seasonal cause of community-acquired pneumonia (CAP). Viral influenza may be caused by influenza A or B and affect any age group. Viral influenza A is usually more severe than influenza B in adults. Viral influenza may present as 3 clinical scenarios: viral influenza alone, viral influenza followed in 1 to 3 days by Staphylococcus aureus pneumonia, or viral influenza followed in 1 to 3 weeks by pneumonia caused by Streptococcus pneumoniae or Haemophilus influenzae. Intravenous drug abusers (IVDAs) are predisposed to a variety of infectious diseases but are not particularly predisposed to viral influenza. We present a case of a young IVDA who presented with influenza A pneumonia who subsequently developed S. pneumoniae CAP. The pneumonococcal suprainfection was severe and prolonged and characterized by a small cavity, empyema, pneumatoceles, and bronchopleural fistulae. S. pneumoniae pleural effusions are uncommon, but pleural empyemas are often demonstrated. Tracheobronchial fistulae and cavitation are rare complications of S. pneumoniae CAP in adults. To the best of our knowledge, this is the first case of post-viral influenza pneumococcal pneumonia in an IVDA. (Heart Lung® 2005;34:222– 6.)
V
iral influenza may be caused by influenza type A or B. Influenza B is more common in children and is usually a milder disease than influenza A. Influenza occurs as outbreaks usually during the winter months, and most often the influenza season peaks in February. The onset of influenza is acute and is accompanied by fever, headaches, myalgias, and severe malaise. Patients often can recall the exact hour that the influenza has affected them. The pneumonia accompanying influenza is a variable severity. The clinical spectrum of viral influenza pneumonia runs from minimal shortness of breath to severe hypoxemia and death. The influenza virus depresses local lung host defenses and predisposes to subsequent bacterial invasion. Patients with influenza pneumonia may present with 1 of 3 distinct clinical scenarios. The first scenario is that of a solitary entity with fever, headaches, myalgias, substernal chest pain, and intercostal muscle involvement mimicking pleuritic From the Infectious Disease Division, Winthrop-University Hospital, Mineola, New York, and State University of New York School of Medicine, Stony Brook, New York. Address for reprints: Burke A. Cunha, MD, Chief, Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501. 0147-9563/$ – see front matter Copyright © 2005 by Mosby Inc. doi:10.1016/j.hrtlng.2004.07.006
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chest pain. The cough is dry and nonproductive. On physical examination, the lungs are silent and the chest radiograph reveals no infiltrates or diffuse bilateral symmetrical haziness. The white blood cell count is either normal or decreased. The second clinical scenario is that of influenza followed 2 to 3 days later by superimposed Staphylococcus aureus bacterial pneumonia. In contrast with patients with only viral influenza pneumonia, these patients have a productive cough and become critically ill within 2 to 3 days. Such patients have central cyanosis and severe hypoxemia. Chest radiograph reveals multiple focal segmental infiltrates with cavitation. Pneumatoceles are common in children, and pneumothoraces or abscesses are common in adults. The patients with this second clinical scenario are the most critically ill and have the highest mortality and morbidity rate. The third clinical scenario is that of influenza that may be followed 1 to 3 weeks after the initial presentation with late bacterial pneumonia. These patients have an interval after their illness of relative stability without clinical deterioration. The late onset of bacterial pneumonia is heralded by a productive cough and recurrence of fever. Such patients are not usually critically ill; they present with community-acquired pneumonia (CAP) and have focal, seg-
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Post-viral influenza Streptococcus pneumoniae pneumonia in an IVDA
Fig 1 Fever pattern and white blood cell count during hospitalization.
mental, or lobar infiltrates without cavitation. The usual organisms causing late bacterial pneumonia after influenza are H. influenzae and S. pneumoniae. Cavitation is not a feature of either S. pneumoniae or H. influenzae CAP. Prognosis is good with appropriate and early antimicrobial therapy.1-6 Pneumococcal CAP usually presents with high fever, rigors, productive cough, and pleuritic chest pain. Radiographic features typically reveal 1 or more segmental or lobar infiltrates. Pleural effusions are uncommon. Diagnosis is suggested by sputum Gram stain or culture. Blood culture results are often positive. Blood culture positivity may be higher in patients with lobar consolidation or air bronchograms. Necrotizing S. pneumoniae is extremely rare.7-10 We report a case of a young male intravenous drug abuser (IVDA) who presented with viral influenza A complicated by late pneumococcal pneumonia with empyema and bronchopleural fistulae.
ILLUSTRATIVE CASE A 25-year-old man presented to the emergency department with a history of fever, malaise, severe myalgias, and shortness of breath for 3 days. The patient was well until 3 days before admission when he began having fevers and malaise. He was seen by his primary care physician, who prescribed oseltamivir for presumed viral influenza, but his symptoms progressed. He developed shortness of breath and a nonproductive dry cough. His fever, myalgias, and shortness of breath continued to worsen until the day of admission. The patient had mild asthma, and he occasionally smoked tobacco and marijuana. He also drank alcohol and was an IVDA of heroin.
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On physical examination, he was afebrile with a blood pressure of 89/54 mm Hg, heart rate of 130 beats/min, and oxygen saturation of 59% on room air. Physical examination revealed tachycardia and bronchial breath sounds with egophony over the entire right lung. His abdomen was soft with mild tenderness diffusely. Laboratory data showed a white blood cell count of 2,300 cells/mm3 (43% bands, 45% neutrophils, 9% lymphocytes, and 3% metamyelocytes). The platelet count was 168,000 K/mm3. Renal function was impaired with blood urea nitrogen of 76 mg/dL and creatinine of 6.3 mg/dL. Liver enzymes were slightly elevated, and erythrocyte sedimentation rate was 114 mm/h (N ⫽ 1-16). A chest radiograph showed right lung consolidation with infiltrates in the left middle and lower lung fields as well as a right pleural effusion. Computed tomography scan of the chest without contrast showed consolidation of the right lung with a left lung infiltrate. An arterial blood gas revealed pH: 7.37 mm Hg, PCO2: 47 mm Hg, PO2: 59.8 mm Hg, and oxygen saturation of 80% on a 100% O2 non-rebreather mask (Fig 1). The patient was intubated, started on pressors for blood pressure support, and given 1 dose of moxifloxacin 400 mg intravenously (IV). He was then transferred to the intensive care unit where he was started on amantadine 100 mg (by mouth) every 12 hours for influenza, cefepime 2 g (IV) every 12 hours, and doxycycline 100 mg (IV) every 12 hours for CAP coverage. A bronchoscopy was performed, and bronchial washings and bronchial lavage were obtained. Bronchial washing and lavage cultures also grew Streptococcus pneumoniae. Blood cultures taken on admission were positive for Streptococcus pneu-
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moniae. Urine pneumococcal antigen test showed negative results. The patient was switched to ceftriaxone 2 g (IV) every 24 hours. On the fourth day, the chest radiograph showed a small developing lucency in the right middle lung. A second computed tomography scan of the chest showed a pneumomediastinum and confluent pneumatoceles in the right middle lung, consistent with cavitary pneumonia. There was an increase in the right pleural empyema and a decrease in the right middle lobe and right lower lobe infiltrates; the left lung showed a progression of infiltrates. The patient’s hospital course was further complicated by a right lung pneumothorax on the fifth day of admission, which was treated with chest tube placement. He also had a right-sided loculated pleural empyema and multiple right bronchopleural fistulae despite continued fevers. The patient began to improve clinically and was extubated on the 19th day of admission. The patient became afebrile on the 23rd hospital day and was discharged on the 32nd day with moxifloxacin 400 mg (by mouth) every 24 hours for an additional 2 weeks. Serologic tests for Epstein-Barr virus; cytomegalovirus; hepatitis A, B, and C viruses; Leptospira; chlamydia; Legionella; mycoplasma; group A streptococcus; and human immunodeficiency virus showed negative results. Initial influenza A antibody titers, negative at the time of admission, became positive (1:16) after 2 weeks. Bronchial washings and blood cultures were positive for S. pneumoniae, but urinary antigen test for S. pneumoniae showed negative results.
DISCUSSION Severe pneumococcal infections occur in patients with asplenia, functional asplenia, and abnormal immunoglobulins such as multiple myeloma, human immunodeficiency virus, and lymphoma. Even in these settings, necrotizing pneumococcal pneumonia is rare because Streptococcus pneumoniae does not produce necrotoxins. Microabscesses are not typical and should raise suspicion of an anatomic abnormality.7,8 Viral influenza pneumonia, particularly viral influenza, may, when severe, be fatal or become complicated by subsequent bacterial superinfection. The onset of viral influenza is sudden and characterized by fever, headache, severe myalgias, and profound malaise. Rhinorrhea, sore throat, and conjunctival suffusion are often present early in the clinical course. Physical examination of the lungs
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reveals no adventitious sounds. The lungs are quiet because viral influenza is an interstitial process that causes an oxygen diffusion defect across the alveolar membrane. Therefore, auscultation does not reveal any sound emanating from the alveoli, which are uninvolved viral influenza. Similarly, the chest radiograph looks deceptively normal or near normal even in very sick individuals. If infiltrates are present at all, they are bilateral, symmetric, perihilar, and interstitial in nature and are barely discernible as minimal diffuse haziness. In severe viral influenza that has progressed, bilateral fluffy infiltrates may develop. Viral influenza affects the respiratory epithelium and decreases local pulmonary host defense mechanisms. The denuded of a respiratory epithelium predisposes to subsequent bacterial invasion. The second clinical presentation of viral influenza pneumonia is that complicated by bacterial super infections that occur 2 to 3 days after the initial presentation of influenza. S. aureus is the most common pathogen responsible for early bacterial infection post-viral influenza pneumonia. Staphylococcal pneumonia is characterized by multiple focal segmental or lobar infiltrates that cavitate within 72 hours. These patients are critically ill and have high fever, are cyanotic, and have a productive cough. The sputum in such patients contains S. aureus, which may be demonstrated by Gram stain or culture. In contrast with viral influenza, in which a normal white blood cell count or leukopenia is the rule, early bacterial super infection post-viral influenza is characterized by a marked leukocytosis. Only 2 organisms can cause rapid cavitation in 72 hours or less, that is, S. aureus and P. aeruginosa. Because P. aeruginosa is not a pathogen that is associated with viral influenza, pneumonia occurring 2 to 3 days after viral influenza accompanied by cyanosis or rapid cavitation should be considered attributable to S. aureus until proven otherwise. The other clinical presentation viral influenza pneumonia is that of late bacterial suprainfection. Patients who present with influenza pneumonia improve somewhat after the initial presentation, but after 1 to 3 weeks, they suddenly develop fever and a productive cough accompanied by leukocytosis. Chest radiograph reveals focal or segmental lobar infiltrates without cavitation. These patients are less critically ill than those with Staphylococcal post-influenza pneumonia. The sputum reveals either pleomorphic gram-negative aerobic bacilli (eg, H. influenzae) or gram-positive diplococci (eg, S. pneumoniae). Because both S. pneumoniae and H. influenzae are bacteremic organisms, blood cultures are frequently positive in CAP caused by either of
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Post-viral influenza Streptococcus pneumoniae pneumonia in an IVDA
Mohan, Nair, and Cunha
Table I Clinical presentations of viral influenza pneumonia
Usual pathogens
Viral Influenza
Influenza followed by early bacterial pneumonia
Influenza followed by late bacterial pneumonia
Influenza virus
Influenza followed by Staphylococcus aureus
Influenza followed by S. pneumoniae or Haemophilus influenzae
Delay after initial None presentation Symptoms Nonproductive dry cough, severe prostration, restlessness, sore throat, headache, myalgias, substernal chest pain, intercostal myalgias, mimicking pleuritic chest pain Signs Conjunctival injection, non-exudative pharyngitis, no rales, hypoxemia, normal breath sounds WBC count Normal/decreased Chest film Normal, no focal/segmental infiltrates, diffuse haziness
2–3 days after clinical presentation Productive cough, sudden deterioration after 2–3 days, critically ill
1–3 weeks after clinical presentation Productive cough, with or without pleuritic chest pain, not critically ill
Central cyanosis, hypotension diffuse rales, severe hypoxemia
Fever recurs after becoming afebrile, localized rales, with or without decreased breath sounds Leukocytosis Lobar consolidation, no cavitation
Marked leukocytes Multiple focal/segmental infiltrates, rapid cavitation, pneumatoceles (children), pneumothorax, multiple abscesses
WBC, White blood cell. Adapted from Cunha BA, Qadir MT. Viral influenza. Infect Disease Pract 1996;20:13.
these pathogens. Bacteremia is part of the pathophysiology of both H. influenzae and S. pneumoniae CAP and should not be viewed as a complication or bad prognostic sign per se. Patients with S. pneumoniae postviral influenza pneumonia are usually less ill and have a less difficult course than those with S. aureus early bacterial pneumonia after viral influenza.5,6,11-15 Our patient was an IVDA and had an unusually severe and protracted course of febrile illness. There are several lessons to be learned from the illustrative case presented. The first lesson is that IVDAs are predisposed to certain infections but may be infected with the same organisms that affect normal hosts, for example, viral influenza. Clinicians should remember that viral influenza might present as 3 distinct clinical scenarios. This case illustrates
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that there is an important difference between early bacterial pneumonia post-viral influenza caused by S. aureus and late bacterial pneumonia post-viral influenza caused by S. pneumoniae or H. influenzae. These differences are described in this article and shown in Table I. Another important point is that S. pneumoniae CAP infrequently is associated with pleural effusion in contrast with what is usually cited in the literature but frequently is complicated by empyema. Cavitation is not a feature of S. pneumoniae CAP. Cavitary S. pneumoniae is exceedingly rare in the literature and occurs most often in children. In adults, “cavitary pneumococcal pneumonia” should be considered attributable to Klebsiella pneumoniae until proven otherwise. K. pneumoniae characteristically cavitates after 3 to 5 days in patients with
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Post-viral influenza Streptococcus pneumoniae pneumonia in an IVDA
Klebsiella CAP. On the rare occasions in which S. pneumoniae does cause cavitation, it usually occurs in children after 3 to 5 days as well. The extreme rarity of cavitation in S. pneumoniae CAP is because S. pneumoniae does not elaborate necrotoxins that are responsible for cavitary lung lesions. In terms of serologic tests at presentation, titers are often negative because the host defenses have not had an adequate time to develop an immune response. In this case, the initial influenza A titers were negative, but 2 weeks later they were elevated at 1:16. The patient was lost to follow-up, and subsequent titers were not available. Urinary antigen tests for various bacteria, Legionella, S. pneumoniae, Escherichia coli, and so forth, are useful if no other diagnostic modality is positive. A negative urinary antigen test result for bacterial pathogens does not rule out infection. The main problem with the urinary antigen test is that it frequently shows negative results initially until sufficient antigen urea occurs to make the test result positive. Positive antigen urea persists for weeks or months, which is the main advantage of urinary antigen diagnostic tests. However, in this case the urinary antigen test result never became positive during the weeks of hospitalization of the patient. Fortunately, the diagnosis was confirmed by bronchial washings, which were positive for S. pneumoniae. Last, our patient had a penicillin-sensitive strain of S. pneumoniae, for example, minimum inhibitory concentration of 0.1 mg/mL or less, and was treated successfully with a variety of antibiotics. Except for highly resistant strains of S. pneumoniae, pneumococci at a minimum inhibitory concentration of 0.8 mg/mL or less still responds to adequately dosed penicillin or beta lactam antibiotics. Our patient was treated with a variety of antibiotics with a high degree of anti-S. pneumoniae activity, and therapy was completed with oral moxifloxacin therapy. Last, the clinical lesson from this case is that although late bacterial pneumonia post-viral influenza is usually less severe than S. aureus, this case indicates that infection with S. pneumoniae may be severe, complicated, and prolonged as in the case of this young IVDA. S. pneumoniae CAP alone or after viral influenza is frequently accompanied by bacteremia, which is
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part of the natural disease process and is not per se a bad prognostic indicator. Another point of interest is the fact that although the patient had blood culture results at admission that were positive for S. pneumoniae, a urinary antigen assay (ie, an enzyme immunoassay test [counterimmunoelectrophoresis]), performed over the course of the admission, had repeatedly negative results. This test has a reported sensitivity and specificity of 93% and 79%, respectively. Our case demonstrates that urinary antigen tests should not be used as a sole method of diagnosis.
REFERENCES 1. Christie AB. Influenza. In: Infectious diseases: epidemiology and clinical practice. New York: Churchill Livingston; 1964. pp. 222-6. 2. Crosby AW. Influenz. In: Kiple KF, editor. The Cambridge world history of human disease. New York: Cambridge University Press; 1993. pp. 807-11. 3. Kilbourne ED, editor. The influenza viruses and influenza. Orlando: Academic Press; 1995. 4. Douglas RG. Jr. Influenza in man. In: Kilbourne ED, editor. The influenza viruses and influenza. Orlando: Academic Press; 1975. pp. 347-395. 5. Louria DB, Blumenfield HL, Ellis JT. Studies on influenza in the pandemic of 1957-1958. II Pulmonary complications of influenza. J Clin Invest 1959;38:213-65. 6. Petersdorf RG, Fusco JJ, Harter DH, et al. Pulmonary infections complicating Asian influenza. Arch Intern Med 1959;103: 262-72. 7. Ort S, Ryan RL, Barden G, et al. Pneumococcal pneumonia in hospitalized patients. JAMA 1983;249:214-8. 8. Watanakunakorn C, Bailey TA. Adult bacteremic pneumococcal pneumonia in a community teaching hospital, 1992-1996. A detailed analysis of 108 cases. Arch Intern Med 1997;157: 1965-71. 9. Yangco BG, Deresinski SC. Necrotizing or cavitating pneumonia due to Streptococcus pneumoniae: report of four cases and review of literature. Medicine 1980;59:449-57. 10. Musher DM, Alexandraki I, Graviss EA, et al. Bacteremia and nonbacteremic pneumococcal pneumonia. A prospective study. Medicine 2000;79:210-21. 11. Heffelfinger JD, Dowell SF, Jorgensen JH, et al. Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group. Arch Intern Med 2001;260:1399-1408. 12. Cunha BA, Qadir MT. Viral influenza. Infect Dis Pract 1996;20:13. 13. Cunha BA. Viral influenza and its complications. Emerg Med 2000;32:56-67. 14. Cunha BA: Severe community-acquired pneumonia. J Crit Illness 1997;12:711-21. 15. Cunha BA. Antibiotic treatment of severe community pneumonia. Semin Respir Crit Care Med 2000;21:61-9.
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