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Case Report: Yersinia enterocolitica Necrotizing Pneumonia in an Immunocompromised Patient
Case Report: Yersinia enterocolitica Necrotizing Pneumonia in an Immunocompromised Patient JOHN N. GREENE, MD,* PATRICK HERNDON, DO,t RAMON L. SANDIN, MD, MS:j:
ABSTRACT: The authors report a rare case of Yersinia enterocolitica necrotizing pneumonia in an immunocompromised patient, who responded with resolution of the infection after 6 weeks of therapy with a third-generation cephalosporin but subsequently expired from the underlying lymphoma. In the few cases of Y. enterocolitica pulmonary infections that have been reported, the prognosis for cure of the infection is excellent with appropriate antibiotic therapy. Y. enterocolitica is likely to be recognized more frequently as a cause of serious infection in the growing immunosuppressed population. Early recognition and appropriate therapy can improve survival significantly. KEY INDEXING TERMS: Y. enterocolitica; Necrotizing pneumonia; immuDocompromised patients. [Am J Med Sci 1993; 305(3):171-173.]
¥
erSinia enterocolitica is a well-known cause of self-limited gastroenteritis, mostly in children, and mesenteric adenitis or terminal ileitis in adolescents and young adults. Rare but rather severe infections are seen with this organism, especially in the immunocompromised host, often without associated gastroenteritis. Reported infections include pneumonia, 1 empyema, 2 lung abscess,1,3 osteomyelitis,2-4 sepsis,5,6 septic arthritis,7 endocarditis,S purulent pericarditis,9 lymphadenitis,lO pharyngitis,n and liver abscess. 12 Although Y. enterocolitica lung abscess has been reported, it is quite rare. We report an immunocompromised paFrom the Department of Medicine, *Division of Infectious and Tropical Diseases, and :j:the Department of Pathology, University of South Florida College of Medicine, Tampa, Florida; and tBay Pines VAMC, Bay Pines, Florida. Correspondence: John Greene, MD, Division of Infectious Diseases, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida, Room 504, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612-9497.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
JEFFREY P. NADLER, MD,*
tient with recurrent lymphoma who developed a necrotizing pneumonia secondary to Y. enterocolitica. Case Report A 62-year·old white man was diagnosed with diffuse histiocytic lymphoma and Waldenstrom's macroglobulinemia after presenting with hepatosplenomegaly, weight loss, weakness, and fatigue. Biopsy· documented lymphoma recurrence was noted in the lung, liver, and stDmach 1 year after the original diagnosis, despite four courses of chem')therapy. The patient developed gradual onset of a nonpro· ductive cough, shortness of breath, and a low grade fever several days after admission for reinduction chemotherapy. He denied sore throat, abdominal pain, !:'Ir diarrhea. His last course of chemotherapy was several weeks prior to admission, with steroids included in the regimen. His past medical history was significant for smoking with chronic obstructive pulmonary disease and a positive purified protein derivative skin test with a negative chest x·ray. He was receiving isoniazid (INH) prophylaxis during the previous 5 months. He had no pets or farm animal contact, denied consumption of unpasteurized dairy products or undercooked meats, and had no recent travel outside the United States. Physical examination revealed an obese man with a temperature of 100° F. The conjunctivae were pale. No oropharyngeal lesions were noted. Decreased breath sounds with dullness to percussion were present in the right upper lung field. No cardiac murmur or rubs were heard. Hepatosplenomegaly and mild right upper quadrant tenderness were noted. No adenopathy, skin rashes, edema, joint abnormalities, or peripheral stigmata of endocarditis were present. Laboratory studies included normal serum electrolytes and liver function tests, except for a total bilirubin of 1.4 mg/dl, albumin 1.9 g/dl, blood urea nitrogen 79 mg/dl, and creatinine 2.8 mg/dl. The white blood cell count was 4200/mm 2 , with 55 polymorphonuclear leukocytes and 24 band forms. The platelet count and hemoglobin were normal. Blood and urine cultures were negative. The chest xray revealed a right upper lobe cavitary infiltrate with an air-fluid level and a large left upper lobe nodule (Figure 1). Computed tomographic scan of the chest and abdomen showed multiple nodular lung lesions, a right upper lobe opacity adjacent to the lateral pleura with air-fluid levels, and hepatosplenomegaly without focal lesions (Figure 2). Adequate sputum specimens could not be obtained. Needle aspiration ofthe left upper lobe nodular lesion revealed lymphoma cells. Aspiration of the right upper lobe fluid-filled cavity revealed gramnegative rods with many polymorphonuclear leukocytes on gram stain. Culture grew Y. enterocolitica sensitive to ampicillin, carben· icillin, cefotaxime, chloramphenicol, tetracycline, trimethoprim-sulfamethoxazole, and gentamicin but resistant to amikacin by disc diffusion method. The patient was treated with 1 g cefotaxime every 8 hours and 600 mg clindamycin every 8 hours intravenously for 6 weeks, with resolution of fever and the left shifted white blood cell count. Chest
171
Y. Enferocolitica Necrotizing Pneumonia
Figure 1. Chest x-ray reveals a right upper lobe cavitary infiltrate with an air-fluid level and a large left upper lobe nodule.
x-ray after 4 weeks of treatment revealed a more diffuse right upper lobe opacity without air-fluid levels and no change in the left upper lobe nodule but interval development of a right pleural effusion. Thoracentesis yielded a straw-colored fluid with a pH of 7.34, white blood count of 30 (predominantly lymphocytic), protein 1.7 gm/dl, normal glucose, negative gram stain and acid-fast bacilli smear, and no growth on culture. The patient received chemotherapy for recurrent lymphoma but died a few weeks later without clinical evidence of recurrent infection. Permission for autopsy was refused.
Discussion
Y. enterocolitica is a facultatively aerobic, nonlactose fermenting, oxidase negative, gram negative coccobacillus of the family Enterobacteriaceae, which is motile at 25° C but not at 38° C. Y. enterocolitica is found worldwide and has been isolated from a variety of animals, meats, dairy products, water, and soil, as well as humans. Most human infections occur from ingestion of contaminated foods, water, or milk, manifesting as gastroenteritis. Y. enterocolitica is most commonly isolated by routine culture onto MacConkey's agar but a higher yield 172
can be obtained with cold enrichment techniques. In fact, the ability of this organism to survive at 4 ° C has posed a new problem to blood banks where red blood cells are stored at that temperature prior to transfusion. Y. enterocolitica bacteremia and endotoxic shock have been recently associated with red blood cell transfusionsY Y. enterocolitica of serogroups generally considered to be nonpathogenic may occasionally be found in the stools of asymptomatic individuals. 14 A positive culture from normally sterile sites outside the gastrointestinal tract or from stool with the appropriate clinical syndrome diagnoses infection due to this organism. Uncomplicated Y. enterocolitica gastroenteritis or mesenteric adenitis in the immunocompetent host is usually self-limited. Extraintestinal infections are uncommon and tend to occur in the immunocompromised or those with liver disease or hemolytic states. Iron overload syndromes such as hemochromatosis or chronic hemolysis tend to increase the virulence of Y. enterocolitica and predispose to systemic infection by making ferric iron, an essential growth factor, more available.5,15 This occurs because Y. enterocolitica lacks the ability to release siderophores, which bind iron and reenter the organism to supply this necessary nutrient for growth.5 ,15 Isolates are usually susceptible to trimethoprimsulfamethoxazole, aminoglycosides, third-generation cephalosporins, or quinolones. They are usually resistant to first-generation cephalosporins and most penicillins. 15 Pulmonary infections caused by Y. enterocolitica are rare with six cases reported previously. 1 Most of those patients were immunocompromised due to alcohol abuse, cirrhosis, or diabetes mellitus. 1 Cavitation of the pulmonary infiltrate occurred in half; half had other sites of infection. All survived with medical treatment. 1 Our case was characteristic: The patient was immunocompromised, developed lung involvement with a necrotizing pneumonia, and responded to appropriate antibiotics. The patient succumbed subsequently to the underlying lymphoma. It could be argued that the patient did not respond to therapy as there was incomplete clearing of the chest x-ray. However, based on clinical grounds, response to therapy was evident, as manifested by defervescence, decrease in the peripheral white blood cell count and left shift, improvement in patient well-being, decrease in cough and shortness of breath, and by the absence of any air-fluid levels on followup x-rays. Although the necrotizing infiltrate was not reaspirated, the pleural effusion aspirate failed to grow any microorganism. A third generation cephalosporin was used to cover the Yersinia isolate, and clindamycin was used for a possible anaerobic bacterial component to the infection. Y. enterocolitica is a rare hut potentially
March 1993 Volume 305 Number 3
Greene et 01
Figure 2. CT scan of the chest and abdomen. Multiple nodular lung lesions were observed, as well as a right upper lobe opacity adjacent to the lateral pleura with air-fluid levels, and hepatosplenomegaly without focal lesions.
dangerous pathogen in immunocompromised patients with necrotizing pneumonia. References 1. Cropp AJ, Gayland SF, Watanakunakom C: Case Report: Cavitary pneumonia due to Y. enterocolitica in a healthy man. Am J Med 288:130-132,1984. 2. Sinnott JT, Multhopp H, Leo J, et al: Y. enterocolitica causing spinal osteomyelitis and empyema in an immunocompromised host. South Med J 82:399-400, 1989. 3. Sebes JI, Mabry EH, Rabinowitz JG: Lung abscess and osteomyelitis of rib due to Y. enterocolitica. Chest 69:546-548, 1976. 4. Fisch A, Prazuck T, Haroche G, et al: Hematogenous osteitis due to Y. enterocolitica. J Infect Dis 160:554, 1989. 5. Cauchie P, Vincken W, Peeters 0, et al: Hemochromatosis and Y. enterocolitica septicemia. Dig Dis Sci 32:1438,1987. 6. Cohen JI, Rodday P: Y. enterocolitica bacteremia in a patient with the acquired immunodeficiency syndrome. Am J Med 86: 254-255, 1989. 7. Taylor BG, Zafarzai MZ, Humphreys DW, et al: Nodular pulmonary infiltrates and septic arthritis associated with
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
8. 9. 10.
11. 12. 13. 14.
15.
Y. enterocolitica bacteremia. Am Rev Resp Dis 116:525-529, 1977. Watanakunakom C: Acute infective endocarditis due to Y. enterocolitica. Am J Med 86:723-724,1989. Lecomte F, Eustache M, Lemeland JF, et al: Purulent pericarditis due to Y. enterocolitica. J Infect Dis 159:363, 1989. Narain JP: Acute inguinal lymphadenitis associated with Y. enterocolitica. South Med J 82:401-1989. Tacket CO, Davis BR, Carter GP, et al: Y. enterocolitica pharyngitis. Ann Intern Med 99:40-42, 1983. Khanna R, Levendoglu H: Liver abscess due to Y. enterocolitica. Case report and review of the literature. Dig Dis Sci 34:636-639, 1989. Woemle CH et al: Yersinia enterocolitica bacteremia and endotoxin shock associated with red blood cell transfusions-U.S., 1991. JAMA 256(17):2174, 1991. Bissett ML, Powers C, Abbott SC, Janda JM: Epidemiologic investigations of Yersinia enterocolitica and related species: Sources, frequency and serogroup distribution. J Clin Microbiol 28(5):910-912, 1990. Cover TL, Aber RC: Y. enterocolitica. N Engl J Med 321:16-24, 1989.
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ABSTRACT: The authors report a rare case of Yersinia enterocolitica necrotizing pneumonia in an immunocompromised patient, who responded with resolution of the infection after 6 weeks of therapy with a third-generation cephalosporin but subsequently expired from the underlying lymphoma. In the few cases of Y. enterocolitica pulmonary infections that have been reported, the prognosis for cure of the infection is excellent with appropriate antibiotic therapy. Y. enterocolitica is likely to be recognized more frequently as a cause of serious infection in the growing immunosuppressed population. Early recognition and appropriate therapy can improve survival significantly. KEY INDEXING TERMS: Y. enterocolitica; Necrotizing pneumonia; immuDocompromised patients. [Am J Med Sci 1993; 305(3):171-173.]
¥
erSinia enterocolitica is a well-known cause of self-limited gastroenteritis, mostly in children, and mesenteric adenitis or terminal ileitis in adolescents and young adults. Rare but rather severe infections are seen with this organism, especially in the immunocompromised host, often without associated gastroenteritis. Reported infections include pneumonia, 1 empyema, 2 lung abscess,1,3 osteomyelitis,2-4 sepsis,5,6 septic arthritis,7 endocarditis,S purulent pericarditis,9 lymphadenitis,lO pharyngitis,n and liver abscess. 12 Although Y. enterocolitica lung abscess has been reported, it is quite rare. We report an immunocompromised paFrom the Department of Medicine, *Division of Infectious and Tropical Diseases, and :j:the Department of Pathology, University of South Florida College of Medicine, Tampa, Florida; and tBay Pines VAMC, Bay Pines, Florida. Correspondence: John Greene, MD, Division of Infectious Diseases, H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida, Room 504, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612-9497.
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
JEFFREY P. NADLER, MD,*
tient with recurrent lymphoma who developed a necrotizing pneumonia secondary to Y. enterocolitica. Case Report A 62-year·old white man was diagnosed with diffuse histiocytic lymphoma and Waldenstrom's macroglobulinemia after presenting with hepatosplenomegaly, weight loss, weakness, and fatigue. Biopsy· documented lymphoma recurrence was noted in the lung, liver, and stDmach 1 year after the original diagnosis, despite four courses of chem')therapy. The patient developed gradual onset of a nonpro· ductive cough, shortness of breath, and a low grade fever several days after admission for reinduction chemotherapy. He denied sore throat, abdominal pain, !:'Ir diarrhea. His last course of chemotherapy was several weeks prior to admission, with steroids included in the regimen. His past medical history was significant for smoking with chronic obstructive pulmonary disease and a positive purified protein derivative skin test with a negative chest x·ray. He was receiving isoniazid (INH) prophylaxis during the previous 5 months. He had no pets or farm animal contact, denied consumption of unpasteurized dairy products or undercooked meats, and had no recent travel outside the United States. Physical examination revealed an obese man with a temperature of 100° F. The conjunctivae were pale. No oropharyngeal lesions were noted. Decreased breath sounds with dullness to percussion were present in the right upper lung field. No cardiac murmur or rubs were heard. Hepatosplenomegaly and mild right upper quadrant tenderness were noted. No adenopathy, skin rashes, edema, joint abnormalities, or peripheral stigmata of endocarditis were present. Laboratory studies included normal serum electrolytes and liver function tests, except for a total bilirubin of 1.4 mg/dl, albumin 1.9 g/dl, blood urea nitrogen 79 mg/dl, and creatinine 2.8 mg/dl. The white blood cell count was 4200/mm 2 , with 55 polymorphonuclear leukocytes and 24 band forms. The platelet count and hemoglobin were normal. Blood and urine cultures were negative. The chest xray revealed a right upper lobe cavitary infiltrate with an air-fluid level and a large left upper lobe nodule (Figure 1). Computed tomographic scan of the chest and abdomen showed multiple nodular lung lesions, a right upper lobe opacity adjacent to the lateral pleura with air-fluid levels, and hepatosplenomegaly without focal lesions (Figure 2). Adequate sputum specimens could not be obtained. Needle aspiration ofthe left upper lobe nodular lesion revealed lymphoma cells. Aspiration of the right upper lobe fluid-filled cavity revealed gramnegative rods with many polymorphonuclear leukocytes on gram stain. Culture grew Y. enterocolitica sensitive to ampicillin, carben· icillin, cefotaxime, chloramphenicol, tetracycline, trimethoprim-sulfamethoxazole, and gentamicin but resistant to amikacin by disc diffusion method. The patient was treated with 1 g cefotaxime every 8 hours and 600 mg clindamycin every 8 hours intravenously for 6 weeks, with resolution of fever and the left shifted white blood cell count. Chest
171
Y. Enferocolitica Necrotizing Pneumonia
Figure 1. Chest x-ray reveals a right upper lobe cavitary infiltrate with an air-fluid level and a large left upper lobe nodule.
x-ray after 4 weeks of treatment revealed a more diffuse right upper lobe opacity without air-fluid levels and no change in the left upper lobe nodule but interval development of a right pleural effusion. Thoracentesis yielded a straw-colored fluid with a pH of 7.34, white blood count of 30 (predominantly lymphocytic), protein 1.7 gm/dl, normal glucose, negative gram stain and acid-fast bacilli smear, and no growth on culture. The patient received chemotherapy for recurrent lymphoma but died a few weeks later without clinical evidence of recurrent infection. Permission for autopsy was refused.
Discussion
Y. enterocolitica is a facultatively aerobic, nonlactose fermenting, oxidase negative, gram negative coccobacillus of the family Enterobacteriaceae, which is motile at 25° C but not at 38° C. Y. enterocolitica is found worldwide and has been isolated from a variety of animals, meats, dairy products, water, and soil, as well as humans. Most human infections occur from ingestion of contaminated foods, water, or milk, manifesting as gastroenteritis. Y. enterocolitica is most commonly isolated by routine culture onto MacConkey's agar but a higher yield 172
can be obtained with cold enrichment techniques. In fact, the ability of this organism to survive at 4 ° C has posed a new problem to blood banks where red blood cells are stored at that temperature prior to transfusion. Y. enterocolitica bacteremia and endotoxic shock have been recently associated with red blood cell transfusionsY Y. enterocolitica of serogroups generally considered to be nonpathogenic may occasionally be found in the stools of asymptomatic individuals. 14 A positive culture from normally sterile sites outside the gastrointestinal tract or from stool with the appropriate clinical syndrome diagnoses infection due to this organism. Uncomplicated Y. enterocolitica gastroenteritis or mesenteric adenitis in the immunocompetent host is usually self-limited. Extraintestinal infections are uncommon and tend to occur in the immunocompromised or those with liver disease or hemolytic states. Iron overload syndromes such as hemochromatosis or chronic hemolysis tend to increase the virulence of Y. enterocolitica and predispose to systemic infection by making ferric iron, an essential growth factor, more available.5,15 This occurs because Y. enterocolitica lacks the ability to release siderophores, which bind iron and reenter the organism to supply this necessary nutrient for growth.5 ,15 Isolates are usually susceptible to trimethoprimsulfamethoxazole, aminoglycosides, third-generation cephalosporins, or quinolones. They are usually resistant to first-generation cephalosporins and most penicillins. 15 Pulmonary infections caused by Y. enterocolitica are rare with six cases reported previously. 1 Most of those patients were immunocompromised due to alcohol abuse, cirrhosis, or diabetes mellitus. 1 Cavitation of the pulmonary infiltrate occurred in half; half had other sites of infection. All survived with medical treatment. 1 Our case was characteristic: The patient was immunocompromised, developed lung involvement with a necrotizing pneumonia, and responded to appropriate antibiotics. The patient succumbed subsequently to the underlying lymphoma. It could be argued that the patient did not respond to therapy as there was incomplete clearing of the chest x-ray. However, based on clinical grounds, response to therapy was evident, as manifested by defervescence, decrease in the peripheral white blood cell count and left shift, improvement in patient well-being, decrease in cough and shortness of breath, and by the absence of any air-fluid levels on followup x-rays. Although the necrotizing infiltrate was not reaspirated, the pleural effusion aspirate failed to grow any microorganism. A third generation cephalosporin was used to cover the Yersinia isolate, and clindamycin was used for a possible anaerobic bacterial component to the infection. Y. enterocolitica is a rare hut potentially
March 1993 Volume 305 Number 3
Greene et 01
Figure 2. CT scan of the chest and abdomen. Multiple nodular lung lesions were observed, as well as a right upper lobe opacity adjacent to the lateral pleura with air-fluid levels, and hepatosplenomegaly without focal lesions.
dangerous pathogen in immunocompromised patients with necrotizing pneumonia. References 1. Cropp AJ, Gayland SF, Watanakunakom C: Case Report: Cavitary pneumonia due to Y. enterocolitica in a healthy man. Am J Med 288:130-132,1984. 2. Sinnott JT, Multhopp H, Leo J, et al: Y. enterocolitica causing spinal osteomyelitis and empyema in an immunocompromised host. South Med J 82:399-400, 1989. 3. Sebes JI, Mabry EH, Rabinowitz JG: Lung abscess and osteomyelitis of rib due to Y. enterocolitica. Chest 69:546-548, 1976. 4. Fisch A, Prazuck T, Haroche G, et al: Hematogenous osteitis due to Y. enterocolitica. J Infect Dis 160:554, 1989. 5. Cauchie P, Vincken W, Peeters 0, et al: Hemochromatosis and Y. enterocolitica septicemia. Dig Dis Sci 32:1438,1987. 6. Cohen JI, Rodday P: Y. enterocolitica bacteremia in a patient with the acquired immunodeficiency syndrome. Am J Med 86: 254-255, 1989. 7. Taylor BG, Zafarzai MZ, Humphreys DW, et al: Nodular pulmonary infiltrates and septic arthritis associated with
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
8. 9. 10.
11. 12. 13. 14.
15.
Y. enterocolitica bacteremia. Am Rev Resp Dis 116:525-529, 1977. Watanakunakom C: Acute infective endocarditis due to Y. enterocolitica. Am J Med 86:723-724,1989. Lecomte F, Eustache M, Lemeland JF, et al: Purulent pericarditis due to Y. enterocolitica. J Infect Dis 159:363, 1989. Narain JP: Acute inguinal lymphadenitis associated with Y. enterocolitica. South Med J 82:401-1989. Tacket CO, Davis BR, Carter GP, et al: Y. enterocolitica pharyngitis. Ann Intern Med 99:40-42, 1983. Khanna R, Levendoglu H: Liver abscess due to Y. enterocolitica. Case report and review of the literature. Dig Dis Sci 34:636-639, 1989. Woemle CH et al: Yersinia enterocolitica bacteremia and endotoxin shock associated with red blood cell transfusions-U.S., 1991. JAMA 256(17):2174, 1991. Bissett ML, Powers C, Abbott SC, Janda JM: Epidemiologic investigations of Yersinia enterocolitica and related species: Sources, frequency and serogroup distribution. J Clin Microbiol 28(5):910-912, 1990. Cover TL, Aber RC: Y. enterocolitica. N Engl J Med 321:16-24, 1989.
173