well have a bacterial pneumonia which was responding to the antibiotic therapy. The patient continued to receive the same drugs, but by four days after admission, he was noted to be definitely more dyspneic. The physical findings remained little changed, the localized rales over the two lobes and the rub over the right middle lobe persisting. No pathogenic organisms were isolated from the sputum, and in view of the lack of response to therapy, it was decided that a more definite diagnosis was needed. On Oct 15, an open biopsy of the right middle lobe was perfonned. On microscopic study of the resected lung, the alveoli were noted to be 6lled with eosinophilic material, which was noted to contain many Pneumocystis organisms when stained with Gomori methamine silver stain. A rare nest of tumor cells was seen in the lymphatic vessels. On Oct 17, the patient started to receive therapy with pentamidine isethionate (200 mg intramuscularly daily); however, he showed little clinical response, and the chest roentgenogram remained unchanged, the lobar in<rates persisting. Death occurred on the seventh day of treatment. At postmortem examination the right middle and left upper lobes showed evidence of consolidation, and Pneumocystia carinii was demonstrated with the silver stain in both lobes. No areas of bacterial pneumonitis were noted, and the postmortem bacterial cultures of the lungs were negative. There were some emphysematous changes throughout the lungs, but no blebs or bullae were present. Occasional tumor cells were seen in the lymphatic vessels of all lobes, but the pleural and subpleural areas were not otherwise involved with the tumor. DISCUSSION

Pneumonia due to Pneumocystis carinii is a potentially curable disease, and, therefore, it is of great importance that clinicians be well familiar with its atypical, as well as its typical, presentations. The case reported here documents for the first time that infection with Pneumocystis may occur as a lobar infiltrate. One other case has been reported in which a lobar distribution of the disease was strongly suspected;· however, in that patient, no biopsy was performed at the time that the lobar distribution was noted, and by the time the etiologic diagnosis was made at postmortem examination 15 days later, there was a patchy infiltrate throughout all the pulmonary fields. Furthermore, the patient had been receiving antibiotic therapy in the interim, which could well have resolved an -associated bacterial lobar pneumonitis. Of further interest in our patient was the presence of a loud pleural rob over one of the involved lobes. No other cause for the rub, such as a pulmonary embolus, bacterial pneumonitis, or pleural involvement with the malignant neoplasm, was demonstrated during the patient's life or at postmortem examination. Thus, a pleural rub must be considered as one of the manifestations of infection with Pneumocystis. The question of whether pneumonitis due toPneumocystis may be associated with pleural effusions remains unanswered. Two of the patients with infections due to Pneumocystis who were reported by Forrest· had effusions, but because of the presence of other possible causes of the effusions, no definite conclusions could be made.

92 GARDNER, PEARSON, HUGHES

As demonstrated by our case-, the infection due to Pneumocystis can closely simulate a bacterial pneumonia with a lobar distribution of the infiltrate seen on the chest roentgenogram and a localized rub heard on physical examination. These observations further broaden the clinical settings in which the clinician must suspect infection with this organism.

.REFERENCES 1 Walzer PC, Perl DP, Krogstad DJ, et al: Pneumocystis carinii pneumonia in the United States. Ann Intern Moo 80:83-93, 1974 2 Burke BA, Good RA: Pneumocystis carini; infection. Medicine 52 :23-51, 1973 3 Cross AS, Steigbigel RT: Pneumocystis carinU pneumonia presenting as localized nodular densities. N Engl J Med 291:831-832, 1974 4 Forrest ]V: Radiographic findings in Pneumocystis carini; pneumonia. Radiology 103:539-544, 1972

Pneumonitis due to Coryne&aderium

.qui* Swan E. Gardner, M.D.; Ted Pearson, M.S.; and Walter T. Hughes, M.D. CorynebtJ€terium equi, a known cause of pneumonitis in foals, calves, and swine, was isolated from the sputum and bronchial washings of a chUd with pneumonitis and leukemia. CUnicai improvement foDowed the administration of chlonmpbenlcol, and cultures of sputum specimens were sterile until relapse occurred after antibiotic therapy was terminated. Cure was achieved with a second course of chlonmphenicol therapy. CorytaebtJ€terium equi was not Isolated from 1,181 samples of sputum from other immunosuppressed chUdren with cancer.

S

orne infectious diseases encountered by immunosuppressed patients have either not been previously reported in the literature or have only been described to a very limited extent. Under these circumstances, single case reports provide a means for accumulation of knowledge on entities rarely encountered, even in large medical centers. The purpose of this report is to describe a case of pneumonia caused by Corynebacterium equi in a child with acute lymphocytic leukemia. Corynebacterium equi is a well-documented cause of pneumonia in calves, 1 foals,2-. and swine, as well as of lymphadenitis in pigs. 5 Two cases in humans have been described, 6, 7 both occurring in adults. ·From the Infectious Diseases Service, St. Jude Children's Research Hospital, Memphis. Supported in part by, Childhood Cancer Research Center grant CA-08480 from the National Cancer Institute, and ALSAC. Reprint requests: Dr. Gardner, St. Jude Children's Research Hospital, Memphis 38101 CHES~

70: 1, JULY, 1976

CASE REpORT

A 13-year-old white boy was diagnosed as having acute lymphocytic leukemia in January 1969. In February 1974, at the age of 18 years, the patient suffered the first of three hematologic relapses, for which he received the following drugs: L-asparaginase, cytosine arabinoside, 6-mercaptopurine, and intrathecally administered methotrexate. On March 12, 1974, the patient had chills and fever. A chest roentgenogram revealed an infiltrate in the left lower lobe. After collection of specimens for culture, oxacillin sodium was given intravenously. The cultures of blood, bone marrow, nasopharynx, urine, and cerebrospinal fluid were ste'rile for bacteria and fungi. Candida albicans was isolated from the throat. On March 13, 1974, the patient was admitted to St. Jude Children's Research Hospital, Memphis. His temperature was 38.2·C (100.8·F), the pul~e rate was 110 beats per minute, the respiratory rate was 24/min, the blood pressure was 110/60 mm Hg, and his weight was 46 kg (100 11». Examination of the mouth revealed lesions of thrush. Persistent rhonchi were heard over the left posterior area of the chest. Retractions were not detectable, and there was no tachypnea. A chest roentgenogram demonstrated a more extensive pneumonia in the left lower lobe than that of the preceding day (Fig 1). The hemoglobin level was 10.2 gm/l00 ml, and the white blood cell count was 7,100/cu mm, with 49 percent polymorphonuclear leukocytes, 44 percent band cells, and 7 percent lymphocytes. There were 9.4 platelets per oil-immersion microscopic field. Cultures of the throat yielded a-hemolytic streptococci, Enterobacter cloacae, and Candida albicans. The same organisms were recovered from the sputum and no acid-fa~t bacilli were isolated. Cultures of blood and urine vielded no growth. Skin tests with purified protein derivative of tuberculin and histoplasmin were nonreactive. Serologic tests detected no antibodies to Aspergillus sp, Histopla'lma capsulatum, Blastomyces dermatitidis, Candidn albicans, and Coccidioides immitis. Because of persistent fever and extension of the pulmonary infiltrate shown on the roentgenogram, therapy with oxacillin

was discontinued on March 14, and 1.9 gm of c1indamycin per day and 2.0 gm of chloramphenicol per day were given intravenously for a total of ten days. Sputum cultures on March 19 and 23 yielded C equi. The patient was afebrile in five days, and the pneumonitis was improved, as shown on the roentgenogram; he was discharged on March 25. The patient remained afebrile, and the sputum cultures failed to grow C equi, but the roentgenogram showed persistent residual atelectasis, pneumonitis, or both, of the left lower lohe. On March 30, 1974, because of an increase in the density in the left lower lobe, bronchoscopic examination was performed, and purulent fluid obtained from the involved bronchus contained C equi by culture. Other organisms obtained from the bronchial wa~hings included small amounts of Staphylococcus aureu.s, a-hemolytic streptococci, and Propionibacterium. A second ten-day course of chloramphenicol was given. The chest roentgenogram was first interpreted as normal on April 23. Repeated sputum cultures after the initiation of antibiotic therapy were sterile. The patient's subsequent course was unrelated to the infection with C equi. On Oct 31,1974, he was admitted with leukemia in relapse, bacterial sepsis, and systemic candidiasis. The patient failed to respond to treatment with oxacillin, gentamicin, carbenicillin, and amphotericin B, and died on Nov 4, 1974. Postmortem examination of the lungs revealed extensive bilateral infarctions. Budding yeast and pseudohyphal forms were demonstrated in the pulmonary parenchyma. Candida albicans was cultured from pulmonary tissue and blood, and Klebsiella pneumoniae was cultured from pulmonary and hepatic specimens. Corynebacterium equi was not cultured from any of the autopsy specimens.

Bacteriologic Findings Isolates from sputum and bronchial washings produced pink mucoid colonies on sheep blood and chocolate (Isovitalex) agars, but not on eosin-methylene blue agar and MacConkey's agar. Gram's stain of the mucoid isolates from the blood agar revealed gram-positive coccoid organisms; however, when the bacteria were cultured in trypticase soy

FIGURE 1. A (left). Air bronchogram showing infiltrate in left lower lobe (art'OlE). B (right), Lateral radiograph showing diaphragm obscured by infiltrate.

CHEST, 70: 1, JULY, 1976

PNEUMONITIS DUE TO CORYNEBACTERIUM EQUI 93

broth, diphtheroid-like bacilli were observed. This pleomorphic characteristic was a clue to the identity of the organism. According to Breed et al,8 C equi exhibits coccoid morphology on solid agar and bacillary form in liquid media. Biochemical tests demonstrated positive reactions for catalase, nitrate reduction, and urease and were nonreactive to cytochrome oxidase and indole. Fermentation of glucose, lactose, sucrose, maltose, mamritol, and xylose did not: occur. The organism was not motile. The identity of the isolate was confirmed as C equi by the Communicable Disease Center in Atlanta. The organism was susceptible to ampicillin, tetracycline, streptomycin, kanamycin, erythromycin, chloramphenicol, .gentamicin, a combination of mmethoprim and sulfamethoxazole, and sulfisoxazole (Gantrisin), using the Kirby-Bauer disk method. Resistance was demonstrated to nitrofurantoin ( Furadantin ), cephalothin, colistin, carbenicillin, penicillin, oxacillin, and methicillin. Over a five-year period from 1970 to 1975, a total of 1,181 samples of sputa from children with leukemia and other forms of cancer were cultured at St. Jude Children's Research Hospital. Corynebacterium equi was isolated only from the patient reported here. DISCUSSION

The three human cases of infection with Corynebacterium equi have several features in common. All were immunosuppressed patients, with lymphosarcoma, 1 lupoid hepatitis, 6 and acute lymphocytic leukemia, respectively, and all received prednisone, as well as other immunosuppressive drugs. The primary infection was in the lung, although one patient also had bacteremia1 and another had a cutaneous lesion. 6 The oral candidiasis in these three patients is not unexpected in such compromised hosts. Corynebacterium equi was isolated from sputum samples but not from the oropharynx. Clinical and bacteriologic responses to antibiotic therapy were prolonged, despite the use of drugs shown by in vitro susceptibility tests to inhibit growth of the organisms at low drug concentrations. In the case of Golub et al,6 two months of therapy with erythromycin (minimum inhibitory concentration, less than O.4p.g/ml) was required to eradicate the pulmonary infection, and recurrent infection in the form of a cutaneous lesion occurred six weeks after the antibiotic therapy was discontinued. In the 39-year-old patient reported by Marsh and von Graevenitz, 7 four weeks of treatment with ampicillin (minimum inhibitory concentration of 3.25p.g/ml) was not adequate to eliminate the organism or to eradicate the disease. The antimicrobial susceptibility patterns of the three isolates are similar. Pulmonary abscesses encountered in the two adult cases were not found in our patient. In the two previous reports of human infections, association of the patients with cattle and swine and their excreta was established. Such a relationship with an animal source was not identified in our patient; however, the natural reservoir of C equi being the soil, invocation of direct animal contact seems unnecessary to explain acquisition of the organism by a child. When the infection was first described in Sweden in 1923, the organism was termed C equi by Magnusson 9 because it was

94 SRIVASTAVA ET Al

recovered from cases of purulent pneumonia in foals. The infection has been reported in calves from Tennessee. I Corynebacterium equi is apparently not a component of the normal flora of the human respiratory tract, since it was not found in 1,181 sputum cultures from immunosuppressed children with cancer at St. Jude Children's Research Hospital. The case reported here emphasizes the point that any organism isolated from the immunosuppressed host must be considered a potential pathogen. The diphtheroid C equi may cause pneumonitis which responds slQwly to antibiotic therapy, and relapse can be expected. REFERENCES

1 Holtman OF: Corynebacterium equi in chronic pneumonia of the calf. J Bacteriol49: 159-162, 1945 2 Dimock WW, Edwards PR: Corynebacterium equi in pneumonia in foals. J Am Vet Med Assoc 79:809-812, 1931 3 Sippel WL, Keahey EE, Bullard TL: Corynebacterium infection in foals: Etiology, pathogenesis, and laboratory diagnosis. J Am Vet Med Assoc 153:1610-1613, 1968 4 Burrow GE: Corynebacterium equi infection in two foals. J Am Vet Med Assoc 152:1119-1124, 1968 5 Karlson AG, Moses HE, Heldman WH: Corynebacterium equi (Magnusson, 1923) in the submaxillary lymph nodes of swine. J Infect Dis 67 :243-251, 1940 6 Golub B, Falk G, Spink WW: Lung abscess due to Corynebacterium equi: Report of first human infection. Ann Intern Med 66:1174-1177,1967 7 Marsh JC, von Graevenitz A: Recurrent Corynebacterium equi infection with lymphoma. Cancer 32:147-149,1973 8 Breed RS, Murray EGO, Smith NR: Bergey's Manual of Determinative Bacteriology (7th ed). Baltimore, William and Wilkins Co, 1957 9 Magnusson H, quoted by Dimock WW, Edwards PR: Corynebacterium equi in pneumonia in foals. J Am Vet Med Assoc 79:809-812, 1931

Echocardiographic Diagnosis of a Stuck Biork-Shiley Aortic Valve Prosthesis* T. Narain Srivastava, M.D.;oO Mohammed Hussain, M.D.;t Laman A. Gray, Jr., M.D.;t and Nancy C. Flowers, M.D., F.C.C.P.§ °From the Section of Cardiology, Department of Medicine, University of Louisville School of Medicine and the Medical Service, Veterans Administration Hospital, Louisville. This study was supported by National Heart and Lung Institute Grant HL-II667, and Public Health Service Grant HL-16901. 00 Assistant Professor of Medicine, Section of Cardiology. tCardiology Fellow. tAssistant .Professor of Surgery and Acting Director, Thoracic and Cardiovascular Surgery. §Professor of Medicine and Chief, Section of Cardiology. Reprint requests: Dr. Srivastava, Section of Cardiology, University of Louisville, Louisville 40202

CHEST, 70: 1, JULY, 1976

Pneumonitis due to Corynebacterium equi.

Corynebacterium equi, a known cause of pneumonitis in foals, calves, and swine, was isolated from the sputum and bronchial washings of a child with pn...
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