Diagnostic Radiology
Etiologic Diagnosis of Focal Pulmonary Infection in Immunocompromised Patients by Fluoroscopically Guided Percutaneous Needle Aspiration 1 Ronald A. Castellino, M;D., and Norman Blank, M.D.
Fluoroscopically guided percutaneous needle aspiration of focal pulmonary lesions was performed in 108 presumed infectious episodes in 82 immunocompromised patients in whom prior diagnostic studies, including transtracheal aspiration, were negative or inconclusive. Two-thirds of the lesions were 4 cm or smaller. Single (61/79) or multiple (18/79) organisms were recovered, for a diagnostic yield of 73% (79/108). Complications were pneumothorax (26 %), half of which required tube drainage, and limited hemoptysis (3 %). This technique can be quickly performed and frequently repeated with existing personnel and equipment in institutions currently employing it for suspected pulmonary neoplasm, and is a productive study in the evaluation of "opportunistic pneumonia". Biopsies, technique. Immunity. Lungs, biopsy, 6[0] .126 • Lungs, infection. Pneumonia. (Lungs, immune deficiency with recurrent infection, 6[0].251)
INDEX TERMS:
Radiology 132:563-567, September 1979
NEUMONIA is still an important cause of morbidity and death in patients who are immunologically compromised due to organ transplantation, underlying neoplasia, irradiation and chemotherapy as treatment for cancer, and congenital or acquired deficiencies of the immune system. Since these pulmonary infections are often rapidly progressive, they should be promptly diagnosed and treated (12). Although the chest radiograph is a very sensitive indicator of pulmonary infection, it lacks specificity, making recognition of the responsible organism(s) impossible by this method alone (3,4). While it is often possible to develop a differential diagnosis from the radiographic appearance, the use of antibiotics or chemotherapeutic drugs to treat all organisms encompassed by the differential diagnosis would be hazardous to the patient. We have found the technique of fluoroscopically guided percutaneous needle aspiration of focal pulmonary lesions suspected to be infectious to be valuable, and present the following data in support.
P
MATERIALS AND METHODS
The technique of fluoroscopically guided percutaneous needle aspiration is similar to that used by many radiologists for the diagnosis of suspected pulmonary neoplasm. The lesion is identified and localized using radiographs in various projections, tomography when necessary, and fluoroscopy. The skin overlying the area to be punctured is prepared and draped. The chest wall and subjacent pleura is then infiltrated with a local anesthetic. Premedication is rarely employed.
We used an 18 gauge thin wall spinal needle for all aspirations reported in this study.The needle tip was inserted inside the lesion as determined by fluoroscopy (often using a "C" arm or a biplane fluoroscope to determine the position of the needle tip in more than one projection). Aspiration was then performed using a 10 ml syringe. If there was a return of fluid or pus, the needle was withdrawn; if not, then 2-5 ml of sterile saline without preservative was rapidly injected and aspirated in an attempt to lavage the area. The aspirated material was transferred immediately to a sealed bottle containing broth under CO2 , with some droplets placed on slides for staining. Specimens were promptly delivered to the laboratories; the cytology technician was often on hand to process the specimens as soon as they were obtained. The material was stained (Gram stain, silver stain, etc.) and cultured both aerobically and anaerobically for bacteria, fungi, and acid-fast organisms. At times, slides were also prepared for cytological evaluation with routine Papanicolaou staining. Contraindications to this technique include uncontrolled bleeding diathysis, severe preexisting respiratory impairment such that pneumothorax could provoke a respiratory crisis, severe pulmonary arterial hypertension, extensive bullous disease, and inability to cooperate. Although it is not possible for the patient to suspend respiration during the entire procedure, it must be suspended for those brief moments when the needle transgresses the pleura and also whenever the needle position is being changed. Throughout other periods of the procedure, shallow respiration is encouraged. Since our early experience (1) with this technique in the late 1960's through March 1978, it has been performed
t From the Division of Diagnostic Radiology,Stanford University School of Medicine, Stanford, Calif. Received Nov. 14, 1978; accepted and revision requested Dec. 29; revision received Feb. 20, 1979. Presented at the Sixty-fourth Scientific Assembly and Annual Meeting of the Radiological Society of North America, Chicago, ilL, Nov. 26-Dec. 1, 1978. as
563
564
RONALD A. CASTELLINO AND NORMAN BLANK
September 1979
c,d
Fig. 1. a-d. A 40-year-old man with immunosuppression secondary to cardiac transplantation. A routine chest radiograph obtained on 5-16 demonstrates a 2.0 X 2.5 cm ovoid nodule in the left upper lobe (arrow), better seen on tomography, which was not present on radiographs two weeks previously. Diagnostic work-up including transtracheal aspiration was negative. Fluoroscopically guided needle aspiration yielded Rhizopus, a member of the Phycomycetes, for which the patient was treated with Amphotericin. A follow-up radiograph obtained on 5-24 shows cavitation of the nodule (arrow) with subsequent resolution over the next several weeks. Three weeks later, fever and joint swelling developed; a chest radiograph obtained on 6-14 demonstrates a large segmental consolidation of the right middle lobe. Percutaneous needle aspiration was again performed because other studies were negative. Mixed anaerobic organisms were recovered for which he was treated with multiple antibiotics. He responded well with eventual radiographic clearing and was alive 29 months after these infectious episodes.
in the radiology department at our institution for the evaluation of 108 presumed pulmonary infectious episodes in 82 immunocompromised patients. In each episode, only one aspiration was performed after the needle was judged to be satisfactorily placed in the lesion. Repeat aspirations were performed rarely days later, following a negative first attempt; however, those results are not included in the present study. Some patients suffered more than one
presumed infectious episode. Such distinct, additional pulmonary infections occurred weeks to months following a prior pulmonary infection, or appeared as new and progressive lesions at the time that other pulmonary lesions were regressing in response to appropriate drugs (Fig. 1). The underlying illnesses or conditions of the patients are summarized in TABLE I. The largest group of patients had
Vol. 132
565
PULMONARY INFECTION IN IMMUNOCOMPROMISED PATIENTS
received cardiac homografts, a reflection of the ongoing cardiac transplantation program at Stanford Medical Center. The age range for all patients was 16-79, with a median of 47 years. Patients included in the study met the following criteria: (a) immunosuppression; (b) the presence of a radiographically and fluoroscopically visible pulmonary abnormality suspected of being an infectious lesion; (c) a prior diagnostic work-up, including transtracheal aspiration, which was negative or inconclusive; and (ei) a pulmonary lesion considered to be focal, including nodules, masses, or segmental consolidations, either single or multiple (as compared to diffuse disease in which most of a lung or both lungs were involved with homogeneous or nonhomogeneous infiltration). The majority of the patients had had recent chest radiographs which indicated that the lesion in question had evolved within a few days or weeks and was therefore probably infectious. However, some patients had chest radiographs months prior to the episode being studied; in these cases, other possibilities such as recurrent or primary neoplasm had to be considered. Following percutaneous needle aspiration, monitoring for complications, especially hemoptysis, was initiated. Serial chest radiographs were obtained over a 24-hour period to detect pneumothorax. The success of the procedure was based upon results of microscopic examination of the specimen both in the bacteriology and surgical pathology (cytology) laboratories, as well as results of culture.
TABLE I:
Diagnostic Radiology
UNDERLYING ILLNESS OR CONDITION IN PATIENTS WHO HAD NEEDLE ASPIRATION
Heart transplantation Renal transplantation Leukemia/lymphoma Solid tumor Steroid therapy Miscellaneous Total
TABLE II:
No. of Patients
No. of Episodes
Underlying Illness or Condition
79 8 13
55
3 3
3
7 12
2
3 2
108
82
RESULTS OF NEEDLE ASPIRATES
Size (cm)
Positive
Negative
Total
6
16 (84%) 36 (73%) 14 (67%) 13 (68%)
3 13 7 6
19 49 21 19
Total
79 (73%)
29
108
Ipsilateral pneumothorax occurred in 28 (26 %) of the procedures as determined by serial postaspiration chest radiographs, with catheter or tube drainage required in 14 (13 %). Hemoptysis, consisting of transient but heavily bloodstained sputum, occurred in 3 (3 %). No major hemorrhage was seen in any patient aspirated with an 18 gauge thin wall needle.
RESULTS
DISCUSSION
Needle aspiration yielded 1 or more etiologic organisms in 79 (73 % ) of 108 presumed infectious episodes. The size of the pulmonary lesion as measured on the radiograph did not appear to influence the yield of positive findings, since even lesions less than 2 em in diameter were productive of diagnostic information at an equivalent or higher level than larger lesions (TABLE II; Figs. 1, a, and 2). Of the 79 positive aspirates, 61 yielded a single organism (TABLE III). Bacteria (26 cases) were almost equally divided between aerobic and anaerobic organisms. In the equally prevalent group of fungi (23 cases), Aspergillus was the predominant subtype. Nocardia (11 cases), a higher bacteria, was also common. Eighteen of the positive aspirates yielded 2 or more organisms (TABLE III), suggestingthat this technique may be effective in detecting mixed infections, not uncommon in these patients. Pulmonary infection due to 1 or more organisms was subsequently established as the cause of the pulmonary lesion by various techniques in 15 of 29 cases with negative aspirates (TABLE IV). In 5 episodes, the lesion in question was subsequently proved not to be an infection; in 1, the aspirated material was interpreted as highly suspicious for malignancy, which was subsequently proved. In the remaining 9 episodes, even though no specific diagnosis was established, the lesions were presumed (although not proved) to be infectious.
The diagnosis and treatment of pulmonary infection in patients with altered immunity from any cause remains a formidable problem (12). Although many antibiotics and chemotherapeutic drugs are effective, none are equally so in treating the wide variety of organisms causing these infections. Not only do many of these drugs have adverse effects on renal function, blood cellular elements, and alteration of the so-called "normal flora", but it is often necessary to carry dose levels to toxicity. Their use should therefore be preceded by attempts to identify the organism(s) responsible for each infectious episode. Immunocompromised patients who develop pulmonary lesions may: (a) have a paucity of symptoms or signs of any kind; (b) be symptomatic, i.e., have cough, fever, sputum production, or pain, but not be critically ill; or (c) be critically ill as judged by the severity of their symptoms and signs, often with severe hypoxemia on ambient air. When a radiographic abnormality is the only compelling sign of active disease, there is often reluctance to interfere with the delicate status of equilibrium attained by the patient. There is an equal or greater reluctance to risk interfering with the already precarious status of the critically ill patient for fear that any additional stress will cause death. Therefore there is a tendency to delay the use of invasive techniques for diagnosis. Anecdotal exceptions notwithstanding, asymptomatic untreated patients can rapidly
566
RONALD
A.
CASTELLINO AND NORMAN BLANK
Fig. 2. A 19-year-old immunosuppressed man with a poorly defined 1.0 cm nodule at the right lung base. He was asymptomatic and recent prior radiographs had been negative. When the diagnostic work-up was nonproductive, percutaneous needle aspiration was performed. Despite the small size of the nodule, the needle tip was placed into the lesion with a subsequent culture of Nocardia from the aspirate. Following treatment with Gantrisin there was complete resolution of the lesion. The patient was alive 27 months following this infectious episode.
TABLE
Ill:
NUMBER AND TYPE OF ORGANISMS YIELDED BY 79 POSITIVE ASPIRATES
Single Organisms (n
= 61)
Bacteria (26) Anaerobic Aerobic Nocardia (11) CMV(1) Fungi (23) Aspergillus Candida Cryptococcus Rhizopus K. fragilis
15 3 3 1 1
MUltiple Organisms (n = 18) 2 in 13 patients 3 in 3 patients 4 in 2 patients
proceed to becoming critically ill and are unlikely to survive without specific therapy. Common techniques for identifying organisms responsible for pulmonary infection include culture and special staining of smears made from specimens of sputum; nasopharyngeal secretions obtained on swabs; tracheobronchial secretions obtained from transtracheal or translaryngeaJ catheterization or bronchoscopy; spec i-
September 1979
mens recovered by percutaneous transthoracic needle aspiration or biopsy; transbronchoscopic biopsy; and open thoracotomy (i, 6, 8-11). Blood cultures are also extremely important, especially in the patient with signs of sepsis. A great advantage of fluoroscopically guided percutaneous needle aspiration is that it can be performed efficiently with existing personnel and equipment in hospitals currently using this technique for the evaluation of suspected pulmonary neoplasm. Considering the magnitude of the clinical problem, the complication rate appears acceptable; the overall incidence of pneumothorax was 26 %, half of which required tube drainage. Significant hemorrhage was not encountered with the noncutting 18 gauge needles used in this study. There were no deaths related to the aspiration. Many of these patients are quite ill due to the underlying disease process or its treatment. Thus they represent a more fragile population than the average patient who undergoes a similar procedure for a pulmonary nodule suspected of being neoplastic. The preaspiration evaluation must determine whether the patient has adequate clotting mechanisms, and hematologic consultation should be liberally obtained. The patient must also be sufficiently alert and cooperative to be able to suspend respiration for five-second periods while the needle is being intermittently advanced into the lesion and fluoroscopically checked. The radiologist must pay meticulous attention to aseptic technique, since contamination of the specimen would provide information misleading to subsequent management of the patient. The aspirated material must be handled carefully in its various stages of collection, preparation, and subsequent culture. Saline without preservative should be used in lavaging the pulmonary lesion since the preservative present in multiuse vials could inhibit the subsequent growth of organisms. We believe it is extremely important to use anaerobic culture techniques in all cases since significant pathogens might otherwise be overlooked. Although it is widely known that growth of M. tuberculosis in a culture requires many days or weeks, it may not be commonly understood that Nocardia organisms can also take days to weeks to grow (5). In recent years we have limited this needle aspiration procedure by the radiologist in the radiology department to those lesions requiring fluoroscopic guidance to ensure that the needle is indeed sampling the area of concern. Bilateral diffuse lesions or those involving large portions of the lung do not require fluoroscopic guidance, and can be sampled in the patient's room by physicians who are willing to learn the technique of percutaneous needle aspiration. This aspect of patient selection explains why we have no cases of P. cerinil pneumonia in this report. (Although we performed needle aspiration in 5 patients with diffuse pulmonary disease upon request of referring physicians, these results were not included in the present study. In 3 of these patients, P. carinii was identified in the aspirate; in 1, C. imltis was recovered; and the fifth was
Vol. 132
PULMONARY INFECTION IN IMMUNOCOMPROMISED PATIENTS
negative, although cytomegalovirus was subsequently cultured from the urine.) Fiberoptic bronchoscopy is an alternate method of obtaining diagnostic information (6, 8, 9, 11). When certain pathogens (e.g., P. carini!) are isolated via this technique, such information is useful. However, the bronchoscope traverses the oropharynx, potentially carrying oral and upper airway flora into the tracheobronchial tree (2,7); thus the recovery of anaerobes and certain gram-negative organisms which may be opportunistic colonizers is of unknown significance. This occurs frequently and appears to be well documented in the literature (2, 7). Sputum samples are likewise unreliable for the diagnosis of infection with anaerobes, since they are normal inhabitants of the oropharynx. The advantage of percutaneous needle aspiration is that it directly samples the area of concern. Positive smears or cultures of aspirated material reflect organisms existent within the pulmonary lesion. Specimens obtained by transtracheal techniques also give reliable culture results and therefore, when positive, can eliminate the need for more invasive methods such as transthoracic needle aspiration. We do not consider the various invasive techniques for obtaining lung specimens as competitive; rather we believe it is important that those responsible for the patient's care cooperate in choosing the best technique for the circumstances. When radiographic and clinical evidence indicates infection to be the probable cause of a focal pulmonary lesion, and transtracheal aspirates have not produced an acceptable organism, percutaneous transthoracic needle aspiration under fluoroscopic guidance is generally justified. If needle aspiration does not facilitate a diagnosis, the procedure can easily be repeated after a short interval, or open thoracotomy can be performed. However, the latter is not as simple an operative procedure for a focal lesion as it is in cases of diffuse pulmonary disease where so-called "minithoracotomy" techniques can be employed, since a larger incision and more extensive exploration may be necessary. In those cases with abnormal coagulation which cannot be corrected, e.g., certain patients with leukemia, open thoracotomy may be preferred as the initial invasive procedure since it offers a better opportunity to control bleeding.
567
Diagnostic Radiology
TABLE IV: CAUSES OF PULMONARY LESIONS AS ESTABLISHED BY VARIOUS TECHNIQUES IN 29 NEGATIVE ASPIRATES Subsequent Proved Infection (15)
2 3 2 4 4
Autopsy Thoracotomy Brushing/washing
TTA Sputum Presumed Infection: No or Empirical Treatment (9) Proved Noninfection (5) Interstitial pneumonitis (thoracotomy) Organizing pneumonitis (thoracotomy) 'Histiocytic lymphoma (thoracotomy t) 'Histiocytic lymphoma (autopsy) Pulmonary infarct (autopsy) 'Cardiac transplant patients.
t Needle aspirate was interpreted as highly suspicious for malig-
nancy.
REFERENCES 1. Bandt PD, Blank N, Castelli no RA: Needle diagnosis of pneumonitis. Value in high-risk patients. JAMA 220:1578-1580,19 Jun 1972 2. Bartlett JG, Alexander J, Mayhew J, et al.: Should fiberoptic bronchoscopy aspirates be cultured? Am Rev Respir Dis 114:73-78, Jul 1976 3. Blank N, Castellino RA: The diagnosis of pulmonary infection in patients with altered immunity. Semin Roentgenol 10:63-72, Jan
1975
ADDENDUM: In a recent report by Wimberley et al. (13) on a catheter with telescoping cannules with a distal occlusion, reliable bacteriologic specimens were obtained viabronchoscopy. Should their experience prove reproducible, a disadvantage of bronchoscopy as noted in the eighth paragraph of the "Discussion" section in this paper may be solved, enhancing the versatility of fiberoptic bronchoscopy in this clinical setting.
4. Blank N, Castelli no RA, Shah V: Radiographic aspects of pulmonary infection in patients with altered immunity. Radiol Clin North Am 11:175-190, Apr 1973 5. Case records of the Massachusetts General Hospital. New Eng J Med 298:154-159, Jan 1978 6. Cunningham JH, Zavala DC, Corry RJ, et al: Trephine air drill, bronchial brush, and fiberoptic transbronchial lung biopsies in immunosuppressed patients. Am Rev Respir Dis 115:213-220, Feb 1977 7. Fossieck BE Jr, Parker RH, Cohen MH, et al: Fiberoptic bronchoscopy and culture of bacteria from the lower respiratory tract. Chest 72:5-9, Jul 1977 8. Hanson RR, Zavala DC, Rhodes ML, et al: Transbronchlal biopsy via flexible fiberoptic bronchoscope; results in 164 patients. Am Rev Respir Dis 114:67-72, Jul 1976 9. Kelley J, Landis IN, Davis GS, et al: Diagnosis of pneumonia due to Pneumocystis by subsegmental pulmonary lavage via the fiberoptic bronchoscope. Chest 74:24-28, Jul 1978 10. Leight GS Jr, Michaelis LL: Open lung biopsy for the diagnosis of acute, diffuse pulmonary infiltrates in the immunosuppressedpatient. Chest 73:477-482, Apr 1978 11. Matthay RA, Farmer WC, Odero D: Diagnostic fiberoptic bronchoscopy in the immunocompromised host with pulmonary infiltrates. Thorax 32:539-545, Oct 1977 12. Williams DM, Krick JA, Remington JS: Pulmonary infection in the compromised host. Parts I and II. Am Rev Respir Dis 114: 359-394, Aug 1976; 114:593-627, Sep 1976 13. Wimberley N, Fating LJ, Bartlett JG: A fiberoptic bronchoscopy technique to obtain uncontaminated lower airway secretions for bacterial culture. Am Rev Respir Dis 119:337-343, Mar 1979
ACKNOWLEDGMENTS: We wish to express our appreciation to Joan Miller, R.N., and Pat Gamberg, R.N., of the Cardiac Transplant Program, for providing clinical information; Patricia Berry, C.T., and her staff, for cytologic support; the residents and faculty members of the Diagnostic Radiology Division, for assisting in some of these procedures; and our clinical colleagues, for referring these patients to us.
Department of Radiology Stanford University Medical Center Stanford, Calif. 94305
Etiologic Diagnosis of Focal Pulmonary Infection in Immunocompromised Patients by Fluoroscopically Guided Percutaneous Needle Aspiration 1 Ronald A. Castellino, M;D., and Norman Blank, M.D.
Fluoroscopically guided percutaneous needle aspiration of focal pulmonary lesions was performed in 108 presumed infectious episodes in 82 immunocompromised patients in whom prior diagnostic studies, including transtracheal aspiration, were negative or inconclusive. Two-thirds of the lesions were 4 cm or smaller. Single (61/79) or multiple (18/79) organisms were recovered, for a diagnostic yield of 73% (79/108). Complications were pneumothorax (26 %), half of which required tube drainage, and limited hemoptysis (3 %). This technique can be quickly performed and frequently repeated with existing personnel and equipment in institutions currently employing it for suspected pulmonary neoplasm, and is a productive study in the evaluation of "opportunistic pneumonia". Biopsies, technique. Immunity. Lungs, biopsy, 6[0] .126 • Lungs, infection. Pneumonia. (Lungs, immune deficiency with recurrent infection, 6[0].251)
INDEX TERMS:
Radiology 132:563-567, September 1979
NEUMONIA is still an important cause of morbidity and death in patients who are immunologically compromised due to organ transplantation, underlying neoplasia, irradiation and chemotherapy as treatment for cancer, and congenital or acquired deficiencies of the immune system. Since these pulmonary infections are often rapidly progressive, they should be promptly diagnosed and treated (12). Although the chest radiograph is a very sensitive indicator of pulmonary infection, it lacks specificity, making recognition of the responsible organism(s) impossible by this method alone (3,4). While it is often possible to develop a differential diagnosis from the radiographic appearance, the use of antibiotics or chemotherapeutic drugs to treat all organisms encompassed by the differential diagnosis would be hazardous to the patient. We have found the technique of fluoroscopically guided percutaneous needle aspiration of focal pulmonary lesions suspected to be infectious to be valuable, and present the following data in support.
P
MATERIALS AND METHODS
The technique of fluoroscopically guided percutaneous needle aspiration is similar to that used by many radiologists for the diagnosis of suspected pulmonary neoplasm. The lesion is identified and localized using radiographs in various projections, tomography when necessary, and fluoroscopy. The skin overlying the area to be punctured is prepared and draped. The chest wall and subjacent pleura is then infiltrated with a local anesthetic. Premedication is rarely employed.
We used an 18 gauge thin wall spinal needle for all aspirations reported in this study.The needle tip was inserted inside the lesion as determined by fluoroscopy (often using a "C" arm or a biplane fluoroscope to determine the position of the needle tip in more than one projection). Aspiration was then performed using a 10 ml syringe. If there was a return of fluid or pus, the needle was withdrawn; if not, then 2-5 ml of sterile saline without preservative was rapidly injected and aspirated in an attempt to lavage the area. The aspirated material was transferred immediately to a sealed bottle containing broth under CO2 , with some droplets placed on slides for staining. Specimens were promptly delivered to the laboratories; the cytology technician was often on hand to process the specimens as soon as they were obtained. The material was stained (Gram stain, silver stain, etc.) and cultured both aerobically and anaerobically for bacteria, fungi, and acid-fast organisms. At times, slides were also prepared for cytological evaluation with routine Papanicolaou staining. Contraindications to this technique include uncontrolled bleeding diathysis, severe preexisting respiratory impairment such that pneumothorax could provoke a respiratory crisis, severe pulmonary arterial hypertension, extensive bullous disease, and inability to cooperate. Although it is not possible for the patient to suspend respiration during the entire procedure, it must be suspended for those brief moments when the needle transgresses the pleura and also whenever the needle position is being changed. Throughout other periods of the procedure, shallow respiration is encouraged. Since our early experience (1) with this technique in the late 1960's through March 1978, it has been performed
t From the Division of Diagnostic Radiology,Stanford University School of Medicine, Stanford, Calif. Received Nov. 14, 1978; accepted and revision requested Dec. 29; revision received Feb. 20, 1979. Presented at the Sixty-fourth Scientific Assembly and Annual Meeting of the Radiological Society of North America, Chicago, ilL, Nov. 26-Dec. 1, 1978. as
563
564
RONALD A. CASTELLINO AND NORMAN BLANK
September 1979
c,d
Fig. 1. a-d. A 40-year-old man with immunosuppression secondary to cardiac transplantation. A routine chest radiograph obtained on 5-16 demonstrates a 2.0 X 2.5 cm ovoid nodule in the left upper lobe (arrow), better seen on tomography, which was not present on radiographs two weeks previously. Diagnostic work-up including transtracheal aspiration was negative. Fluoroscopically guided needle aspiration yielded Rhizopus, a member of the Phycomycetes, for which the patient was treated with Amphotericin. A follow-up radiograph obtained on 5-24 shows cavitation of the nodule (arrow) with subsequent resolution over the next several weeks. Three weeks later, fever and joint swelling developed; a chest radiograph obtained on 6-14 demonstrates a large segmental consolidation of the right middle lobe. Percutaneous needle aspiration was again performed because other studies were negative. Mixed anaerobic organisms were recovered for which he was treated with multiple antibiotics. He responded well with eventual radiographic clearing and was alive 29 months after these infectious episodes.
in the radiology department at our institution for the evaluation of 108 presumed pulmonary infectious episodes in 82 immunocompromised patients. In each episode, only one aspiration was performed after the needle was judged to be satisfactorily placed in the lesion. Repeat aspirations were performed rarely days later, following a negative first attempt; however, those results are not included in the present study. Some patients suffered more than one
presumed infectious episode. Such distinct, additional pulmonary infections occurred weeks to months following a prior pulmonary infection, or appeared as new and progressive lesions at the time that other pulmonary lesions were regressing in response to appropriate drugs (Fig. 1). The underlying illnesses or conditions of the patients are summarized in TABLE I. The largest group of patients had
Vol. 132
565
PULMONARY INFECTION IN IMMUNOCOMPROMISED PATIENTS
received cardiac homografts, a reflection of the ongoing cardiac transplantation program at Stanford Medical Center. The age range for all patients was 16-79, with a median of 47 years. Patients included in the study met the following criteria: (a) immunosuppression; (b) the presence of a radiographically and fluoroscopically visible pulmonary abnormality suspected of being an infectious lesion; (c) a prior diagnostic work-up, including transtracheal aspiration, which was negative or inconclusive; and (ei) a pulmonary lesion considered to be focal, including nodules, masses, or segmental consolidations, either single or multiple (as compared to diffuse disease in which most of a lung or both lungs were involved with homogeneous or nonhomogeneous infiltration). The majority of the patients had had recent chest radiographs which indicated that the lesion in question had evolved within a few days or weeks and was therefore probably infectious. However, some patients had chest radiographs months prior to the episode being studied; in these cases, other possibilities such as recurrent or primary neoplasm had to be considered. Following percutaneous needle aspiration, monitoring for complications, especially hemoptysis, was initiated. Serial chest radiographs were obtained over a 24-hour period to detect pneumothorax. The success of the procedure was based upon results of microscopic examination of the specimen both in the bacteriology and surgical pathology (cytology) laboratories, as well as results of culture.
TABLE I:
Diagnostic Radiology
UNDERLYING ILLNESS OR CONDITION IN PATIENTS WHO HAD NEEDLE ASPIRATION
Heart transplantation Renal transplantation Leukemia/lymphoma Solid tumor Steroid therapy Miscellaneous Total
TABLE II:
No. of Patients
No. of Episodes
Underlying Illness or Condition
79 8 13
55
3 3
3
7 12
2
3 2
108
82
RESULTS OF NEEDLE ASPIRATES
Size (cm)
Positive
Negative
Total
6
16 (84%) 36 (73%) 14 (67%) 13 (68%)
3 13 7 6
19 49 21 19
Total
79 (73%)
29
108
Ipsilateral pneumothorax occurred in 28 (26 %) of the procedures as determined by serial postaspiration chest radiographs, with catheter or tube drainage required in 14 (13 %). Hemoptysis, consisting of transient but heavily bloodstained sputum, occurred in 3 (3 %). No major hemorrhage was seen in any patient aspirated with an 18 gauge thin wall needle.
RESULTS
DISCUSSION
Needle aspiration yielded 1 or more etiologic organisms in 79 (73 % ) of 108 presumed infectious episodes. The size of the pulmonary lesion as measured on the radiograph did not appear to influence the yield of positive findings, since even lesions less than 2 em in diameter were productive of diagnostic information at an equivalent or higher level than larger lesions (TABLE II; Figs. 1, a, and 2). Of the 79 positive aspirates, 61 yielded a single organism (TABLE III). Bacteria (26 cases) were almost equally divided between aerobic and anaerobic organisms. In the equally prevalent group of fungi (23 cases), Aspergillus was the predominant subtype. Nocardia (11 cases), a higher bacteria, was also common. Eighteen of the positive aspirates yielded 2 or more organisms (TABLE III), suggestingthat this technique may be effective in detecting mixed infections, not uncommon in these patients. Pulmonary infection due to 1 or more organisms was subsequently established as the cause of the pulmonary lesion by various techniques in 15 of 29 cases with negative aspirates (TABLE IV). In 5 episodes, the lesion in question was subsequently proved not to be an infection; in 1, the aspirated material was interpreted as highly suspicious for malignancy, which was subsequently proved. In the remaining 9 episodes, even though no specific diagnosis was established, the lesions were presumed (although not proved) to be infectious.
The diagnosis and treatment of pulmonary infection in patients with altered immunity from any cause remains a formidable problem (12). Although many antibiotics and chemotherapeutic drugs are effective, none are equally so in treating the wide variety of organisms causing these infections. Not only do many of these drugs have adverse effects on renal function, blood cellular elements, and alteration of the so-called "normal flora", but it is often necessary to carry dose levels to toxicity. Their use should therefore be preceded by attempts to identify the organism(s) responsible for each infectious episode. Immunocompromised patients who develop pulmonary lesions may: (a) have a paucity of symptoms or signs of any kind; (b) be symptomatic, i.e., have cough, fever, sputum production, or pain, but not be critically ill; or (c) be critically ill as judged by the severity of their symptoms and signs, often with severe hypoxemia on ambient air. When a radiographic abnormality is the only compelling sign of active disease, there is often reluctance to interfere with the delicate status of equilibrium attained by the patient. There is an equal or greater reluctance to risk interfering with the already precarious status of the critically ill patient for fear that any additional stress will cause death. Therefore there is a tendency to delay the use of invasive techniques for diagnosis. Anecdotal exceptions notwithstanding, asymptomatic untreated patients can rapidly
566
RONALD
A.
CASTELLINO AND NORMAN BLANK
Fig. 2. A 19-year-old immunosuppressed man with a poorly defined 1.0 cm nodule at the right lung base. He was asymptomatic and recent prior radiographs had been negative. When the diagnostic work-up was nonproductive, percutaneous needle aspiration was performed. Despite the small size of the nodule, the needle tip was placed into the lesion with a subsequent culture of Nocardia from the aspirate. Following treatment with Gantrisin there was complete resolution of the lesion. The patient was alive 27 months following this infectious episode.
TABLE
Ill:
NUMBER AND TYPE OF ORGANISMS YIELDED BY 79 POSITIVE ASPIRATES
Single Organisms (n
= 61)
Bacteria (26) Anaerobic Aerobic Nocardia (11) CMV(1) Fungi (23) Aspergillus Candida Cryptococcus Rhizopus K. fragilis
15 3 3 1 1
MUltiple Organisms (n = 18) 2 in 13 patients 3 in 3 patients 4 in 2 patients
proceed to becoming critically ill and are unlikely to survive without specific therapy. Common techniques for identifying organisms responsible for pulmonary infection include culture and special staining of smears made from specimens of sputum; nasopharyngeal secretions obtained on swabs; tracheobronchial secretions obtained from transtracheal or translaryngeaJ catheterization or bronchoscopy; spec i-
September 1979
mens recovered by percutaneous transthoracic needle aspiration or biopsy; transbronchoscopic biopsy; and open thoracotomy (i, 6, 8-11). Blood cultures are also extremely important, especially in the patient with signs of sepsis. A great advantage of fluoroscopically guided percutaneous needle aspiration is that it can be performed efficiently with existing personnel and equipment in hospitals currently using this technique for the evaluation of suspected pulmonary neoplasm. Considering the magnitude of the clinical problem, the complication rate appears acceptable; the overall incidence of pneumothorax was 26 %, half of which required tube drainage. Significant hemorrhage was not encountered with the noncutting 18 gauge needles used in this study. There were no deaths related to the aspiration. Many of these patients are quite ill due to the underlying disease process or its treatment. Thus they represent a more fragile population than the average patient who undergoes a similar procedure for a pulmonary nodule suspected of being neoplastic. The preaspiration evaluation must determine whether the patient has adequate clotting mechanisms, and hematologic consultation should be liberally obtained. The patient must also be sufficiently alert and cooperative to be able to suspend respiration for five-second periods while the needle is being intermittently advanced into the lesion and fluoroscopically checked. The radiologist must pay meticulous attention to aseptic technique, since contamination of the specimen would provide information misleading to subsequent management of the patient. The aspirated material must be handled carefully in its various stages of collection, preparation, and subsequent culture. Saline without preservative should be used in lavaging the pulmonary lesion since the preservative present in multiuse vials could inhibit the subsequent growth of organisms. We believe it is extremely important to use anaerobic culture techniques in all cases since significant pathogens might otherwise be overlooked. Although it is widely known that growth of M. tuberculosis in a culture requires many days or weeks, it may not be commonly understood that Nocardia organisms can also take days to weeks to grow (5). In recent years we have limited this needle aspiration procedure by the radiologist in the radiology department to those lesions requiring fluoroscopic guidance to ensure that the needle is indeed sampling the area of concern. Bilateral diffuse lesions or those involving large portions of the lung do not require fluoroscopic guidance, and can be sampled in the patient's room by physicians who are willing to learn the technique of percutaneous needle aspiration. This aspect of patient selection explains why we have no cases of P. cerinil pneumonia in this report. (Although we performed needle aspiration in 5 patients with diffuse pulmonary disease upon request of referring physicians, these results were not included in the present study. In 3 of these patients, P. carinii was identified in the aspirate; in 1, C. imltis was recovered; and the fifth was
Vol. 132
PULMONARY INFECTION IN IMMUNOCOMPROMISED PATIENTS
negative, although cytomegalovirus was subsequently cultured from the urine.) Fiberoptic bronchoscopy is an alternate method of obtaining diagnostic information (6, 8, 9, 11). When certain pathogens (e.g., P. carini!) are isolated via this technique, such information is useful. However, the bronchoscope traverses the oropharynx, potentially carrying oral and upper airway flora into the tracheobronchial tree (2,7); thus the recovery of anaerobes and certain gram-negative organisms which may be opportunistic colonizers is of unknown significance. This occurs frequently and appears to be well documented in the literature (2, 7). Sputum samples are likewise unreliable for the diagnosis of infection with anaerobes, since they are normal inhabitants of the oropharynx. The advantage of percutaneous needle aspiration is that it directly samples the area of concern. Positive smears or cultures of aspirated material reflect organisms existent within the pulmonary lesion. Specimens obtained by transtracheal techniques also give reliable culture results and therefore, when positive, can eliminate the need for more invasive methods such as transthoracic needle aspiration. We do not consider the various invasive techniques for obtaining lung specimens as competitive; rather we believe it is important that those responsible for the patient's care cooperate in choosing the best technique for the circumstances. When radiographic and clinical evidence indicates infection to be the probable cause of a focal pulmonary lesion, and transtracheal aspirates have not produced an acceptable organism, percutaneous transthoracic needle aspiration under fluoroscopic guidance is generally justified. If needle aspiration does not facilitate a diagnosis, the procedure can easily be repeated after a short interval, or open thoracotomy can be performed. However, the latter is not as simple an operative procedure for a focal lesion as it is in cases of diffuse pulmonary disease where so-called "minithoracotomy" techniques can be employed, since a larger incision and more extensive exploration may be necessary. In those cases with abnormal coagulation which cannot be corrected, e.g., certain patients with leukemia, open thoracotomy may be preferred as the initial invasive procedure since it offers a better opportunity to control bleeding.
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Diagnostic Radiology
TABLE IV: CAUSES OF PULMONARY LESIONS AS ESTABLISHED BY VARIOUS TECHNIQUES IN 29 NEGATIVE ASPIRATES Subsequent Proved Infection (15)
2 3 2 4 4
Autopsy Thoracotomy Brushing/washing
TTA Sputum Presumed Infection: No or Empirical Treatment (9) Proved Noninfection (5) Interstitial pneumonitis (thoracotomy) Organizing pneumonitis (thoracotomy) 'Histiocytic lymphoma (thoracotomy t) 'Histiocytic lymphoma (autopsy) Pulmonary infarct (autopsy) 'Cardiac transplant patients.
t Needle aspirate was interpreted as highly suspicious for malig-
nancy.
REFERENCES 1. Bandt PD, Blank N, Castelli no RA: Needle diagnosis of pneumonitis. Value in high-risk patients. JAMA 220:1578-1580,19 Jun 1972 2. Bartlett JG, Alexander J, Mayhew J, et al.: Should fiberoptic bronchoscopy aspirates be cultured? Am Rev Respir Dis 114:73-78, Jul 1976 3. Blank N, Castellino RA: The diagnosis of pulmonary infection in patients with altered immunity. Semin Roentgenol 10:63-72, Jan
1975
ADDENDUM: In a recent report by Wimberley et al. (13) on a catheter with telescoping cannules with a distal occlusion, reliable bacteriologic specimens were obtained viabronchoscopy. Should their experience prove reproducible, a disadvantage of bronchoscopy as noted in the eighth paragraph of the "Discussion" section in this paper may be solved, enhancing the versatility of fiberoptic bronchoscopy in this clinical setting.
4. Blank N, Castelli no RA, Shah V: Radiographic aspects of pulmonary infection in patients with altered immunity. Radiol Clin North Am 11:175-190, Apr 1973 5. Case records of the Massachusetts General Hospital. New Eng J Med 298:154-159, Jan 1978 6. Cunningham JH, Zavala DC, Corry RJ, et al: Trephine air drill, bronchial brush, and fiberoptic transbronchial lung biopsies in immunosuppressed patients. Am Rev Respir Dis 115:213-220, Feb 1977 7. Fossieck BE Jr, Parker RH, Cohen MH, et al: Fiberoptic bronchoscopy and culture of bacteria from the lower respiratory tract. Chest 72:5-9, Jul 1977 8. Hanson RR, Zavala DC, Rhodes ML, et al: Transbronchlal biopsy via flexible fiberoptic bronchoscope; results in 164 patients. Am Rev Respir Dis 114:67-72, Jul 1976 9. Kelley J, Landis IN, Davis GS, et al: Diagnosis of pneumonia due to Pneumocystis by subsegmental pulmonary lavage via the fiberoptic bronchoscope. Chest 74:24-28, Jul 1978 10. Leight GS Jr, Michaelis LL: Open lung biopsy for the diagnosis of acute, diffuse pulmonary infiltrates in the immunosuppressedpatient. Chest 73:477-482, Apr 1978 11. Matthay RA, Farmer WC, Odero D: Diagnostic fiberoptic bronchoscopy in the immunocompromised host with pulmonary infiltrates. Thorax 32:539-545, Oct 1977 12. Williams DM, Krick JA, Remington JS: Pulmonary infection in the compromised host. Parts I and II. Am Rev Respir Dis 114: 359-394, Aug 1976; 114:593-627, Sep 1976 13. Wimberley N, Fating LJ, Bartlett JG: A fiberoptic bronchoscopy technique to obtain uncontaminated lower airway secretions for bacterial culture. Am Rev Respir Dis 119:337-343, Mar 1979
ACKNOWLEDGMENTS: We wish to express our appreciation to Joan Miller, R.N., and Pat Gamberg, R.N., of the Cardiac Transplant Program, for providing clinical information; Patricia Berry, C.T., and her staff, for cytologic support; the residents and faculty members of the Diagnostic Radiology Division, for assisting in some of these procedures; and our clinical colleagues, for referring these patients to us.
Department of Radiology Stanford University Medical Center Stanford, Calif. 94305
