- Email: [email protected]
Citrobacter diversus Endocarditis
Citrobacter diversus Endocarditis ILDEFONSO TELLEZ, MD; GEORGE S. CHRYSANT, MD; IMAD OMER, MD; WILLIAM E. DISMUKES, MD
ABSTRACT: Citrobacter species are motile Gram-negative bacilli that cause disease in humans, such as urinary tract infection, pneumonia, superficial and deep wound infections, gastroenteritis, meningitis, bacteremia, and rarely endocarditis. In those cases of endocarditis, intravenous drug use has been associated with Citrobacter species. Gram-negative organisms are present in less
than 10% of cases of endocarditis in intravenous drug users. We present a case of tricuspid valve endocarditis in an intravenous drug user caused by Citrobacter diversus alone. KEY INDEXING TERMS: Right-sided endocarditis; Intravenous drug use; Citrobacter diversus; Bacterial endocarditis. [Am J Med Sci 2000;1(6):408–410.]
T
discharged on oral amoxicillin/clavulanic acid and 12 days later was readmitted to the hospital for a second time because of bilateral lower extremity cellulitis and fever. White blood count was 7,900/ mm3. Blood cultures again grew Citrobacter diversus, with the same susceptibility pattern as the previous isolate; no other organism was identified. MRI of the feet was negative for osteomyelitis, and an abdominal CT scan revealed no pathologic lesions. The patient once again refused a transesophageal echocardiogram. He was treated with intravenous ceftriaxone and gentamicin for 10 days, the cellulitis improved, and repeat blood cultures were once again negative for any organism. He was discharged on a 2-week course of oral trimethoprim-sulfamethoxazole. The patient alleged compliance and seemed to be well over the next 6 weeks, but then he developed fevers up to 103°F, rigors, and a nonproductive cough with left-sided pleuritic chest pain. He presented to the clinic, where a chest radiograph revealed pneumonia with cavitation. A diagnosis of community-acquired pneumonia was made and the patient was readmitted to the hospital for the third time in 3 months. Physical examination revealed a disheveled male in no apparent distress, with a blood pressure of 122/64 mm Hg, heart rate of 104 beats per minute, regular respiratory rate of 24 per minute, and a temperature of 102.7°F. Findings included tenderness over the left lateral chest wall, rhonchi over the left upper lobe, a new, soft II/VI systolic murmur at the left lower sternal border, and limitation of motion of the right shoulder with no erythema, warmth, or effusion noted. There were no conjunctival petechiae, Roth spots, splinter hemorrhages, or Osler nodes. Neurologic examination was normal. The white blood count was 13,600/mm3, and hematocrit was 0.315. Arterial blood gas results were PaO2 77 mm Hg, PCO2 35 mm Hg, pH 7.51, and O2 saturation of 94% on room air. Chemistry profile and liver enzymes were within normal limits. Erythrocyte sedimentation rate was 75 mm/hour. The chest radiograph revealed an infiltrate with a 3- ⫻ 2-cm cavitation in the left upper pulmonary lobe consistent with a necrotizing pneumonia. A transthoracic echocardiogram revealed a new mobile echodensity on the tricuspid valve, consistent with vegetation, and grade 3/4 tricuspid regurgitation. Patient was initially treated with vancomycin and ticarcillin/clavulanic acid for presumed right-sided endocarditis and pneumonia. The antibiotic regimen was changed to ticarcillin/clavulanic acid plus gentamicin when blood cultures revealed Gram-negative bacilli. Final identification of sputum and blood culture isolates showed C diversus, with the same susceptibility pattern as in the two previous admissions. After an improvement in his clinical condition, resolution of pneumonia, and negative repeat blood cultures, the patient was discharged on oral ciprofloxacin for an additional 3 weeks of therapy. (Fig. 1).
he genus Citrobacter includes aerobic, Gramnegative bacilli that can be found in soil, food, and water and that are able to cause serious infections in humans involving the urinary, gastrointestinal and respiratory tracts and the central nervous system.1 Citrobacter species have also been reported as a rare cause of bacteremia and endocarditis in narcotic addicts.2 There are three species in the genus Citrobacter: C amalonaticus, C diversus, and C freundii. Here, we describe a case of tricuspid valve endocarditis in an intravenous drug user (IVDU) caused by Citrobacter diversus alone. Case Report A 51-year-old man was admitted to the hospital because of a 10-day history of fever, chills, right shoulder pain, and left-sided pleuritic chest pain. His past medical history was significant only for bilateral transmetatarsal amputations 20 years earlier because of frostbite. He reported a history of intravenous drug use over the past 20 years, unprotected heterosexual activities with several partners, and current use of alcohol, cocaine, and marijuana. Three months before presentation, he had been admitted with left shoulder pain and fevers up to 102.5° F. Purified protein derivative (tuberculin) skin test was normal and serum was negative for HIV. Cultures of both an aspirate of the shoulder joint and urine were negative for bacterial growth. However, blood cultures grew group G streptococci and Citrobacter diversus, sensitive to tobramycin, gentamicin, trimethoprim-sulfamethoxazole, ticarcillin, ofloxacin and cephalosporins. There was no heart murmur, and a transthoracic echocardiogram did not reveal vegetations or other abnormalities. The patient declined a transesophageal echocardiogram. After 8 days of intravenous antibiotic therapy with gentamicin, ceftriaxone, and vancomycin, repeated blood cultures were negative. The patient was
From the Division of Infectious Diseases (IT, IO, WED), Department of Medicine (GSC), University of Alabama at Birmingham, Birmingham, Alabama. Submitted May 10, 2000; accepted August 16, 2000. Correspondence: Dr. William E. Dismukes, Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, 1900 Univ. Blvd., 229 THT. Birmingham, AL 35294-0006.
408
December 2000 Volume 320 Number 6
Tellez et al
Figure 1. Clinical course during the patient’s hospitalizations. First admission: patient had left shoulder pain and fever. Blood cultures were positive for group G streptococci and C diversus. Second admission: patient presented with bilateral lower extremity cellulitis and fever. Blood cultures again grew C diversus. Third admission: patient presented with pneumonia, fever, and a heart murmur. Sputum and blood cultures were positive for C diversus. A transthoracic echocardiogram revealed a vegetation on the tricuspid valve. WBC, white blood count; BlCx, blood cultures; Cx, culture; Neg, negative; TTE, transthoracic echocardiogram; L, left; R, right; LE, lower extremity.
Discussion Right-sided valvular infective endocarditis is frequently a disease of IVDU. Bacterial endocarditis in this population has been estimated to be 1.5 to 20 per 1000 addicts per year.3,4 Several mechanisms have been proposed to explain the increased prevalence of right-sided endocarditis among IVDU.5 These include valvular endothelial injury, physiologic effects of injected substances, characteristics of the particular infective agent, and the host’s immune responses. Staphylococcus aureus has been the organism most commonly isolated in right-sided, addict-associated endocarditis, followed by streptococci (groups A, B, and G).6,7 Gram-negative organisms account for 4.8 to 7.5% of these cases; in this group, Pseudomonas aeruginosa predominates. C freundii and C diversus (formerly C THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
koseri) have been described as rare causes of mitral and aortic valve endocarditis, respectively.8–9 Susceptibility patterns are different according to the Citrobacter species. For example, C diversus is usually sensitive to aminoglycoside drugs, trimethoprim-sulfamethoxazole, cephalothin, and, to a lesser degree, tetracycline.1 Our case is the first reported to date of an IVDU with tricuspid valve endocarditis caused by C diversus alone. Our patient probably acquired his Citrobacter infection while abusing drugs weeks to months before his first hospitalization. It is likely that the patient was not compliant while on oral antibiotic therapy. The findings of pleuritic chest pain, pulmonary infiltrate with cavitation, and left shoulder pain are common in IVDUs with endocarditis.10,11 By contrast, an indolent course with repeated admissions 409
Citrobacter diversus Endocarditis
for unexplained bacteremia in an IVDU should raise a high index of suspicion for right-sided endocarditis. Once the diagnosis is established, antibiotic treatment should continue for a minimum of at least 4 weeks, even in the absence of vegetation on a transthoracic or transesophageal echocardiogram. References 1. Lipsky BA, Hook ED III, Smith AA, et al. Citrobacter infections in humans: experience at the Seattle Veterans Administration Medical Center and a review of the literature. Rev Infect Dis 1980;2:746 – 60. 2. Crane LR, Levine DP, Zervos MJ, et al. Bacteremia in narcotic addicts at the Detroit Medical Center. I. Microbiology, epidemiology, risk factors and empiric therapy. Rev Infect Dis 1986;8:364 –73. 3. Levine DP, Crane LR, Zervos MJ. Bacteremia in narcotic addicts at the Detroit Medical Center. II. Infectious endocarditis: a prospective comparative study. Rev Infect Dis 1986; 8:374 –96.
410
4. Chan P, Ogilby ID, Segal B. Tricuspid valve endocarditis. Am Heart J 1989;117:1140 – 6. 5. Frontera JA, Gradon JD. Right-side endocarditis in injection drug users: review of proposed mechanisms of pathogenesis. Clin Infect Dis 2000;30:374 –9. 6. Chambers HF, Korzeniowski OM, Sande MA. Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts. Medicine 1983;62:170 –7. 7. Hecht SR, Berger M. Right-sided endocarditis in intravenous drug users. Ann Intern Med 1992;117:560 – 6. 8. Plantholt SJ, Trofa AF. Citrobacter freundii endocarditis in an intravenous drug abuser. South Med J.;1987;80: 1439 – 41. 9. MacCulloch D, Menzies R, Cornere BM. Endocarditis due to Citrobacter diversus developing resistance to cephalothin. N Z Med J 1977;85:182–3. 10. Cunha BA. Endocarditis in the narcotic addict. Infect Dis Clin Pract 1986;10:1– 8. 11. Robbins MJ, Soeiro R, Frishman WH. Right sided valvular endocarditis: etiology, diagnosis, and an approach to therapy. Am Heart J 1986;111:128 –35.
December 2000 Volume 320 Number 6
ABSTRACT: Citrobacter species are motile Gram-negative bacilli that cause disease in humans, such as urinary tract infection, pneumonia, superficial and deep wound infections, gastroenteritis, meningitis, bacteremia, and rarely endocarditis. In those cases of endocarditis, intravenous drug use has been associated with Citrobacter species. Gram-negative organisms are present in less
than 10% of cases of endocarditis in intravenous drug users. We present a case of tricuspid valve endocarditis in an intravenous drug user caused by Citrobacter diversus alone. KEY INDEXING TERMS: Right-sided endocarditis; Intravenous drug use; Citrobacter diversus; Bacterial endocarditis. [Am J Med Sci 2000;1(6):408–410.]
T
discharged on oral amoxicillin/clavulanic acid and 12 days later was readmitted to the hospital for a second time because of bilateral lower extremity cellulitis and fever. White blood count was 7,900/ mm3. Blood cultures again grew Citrobacter diversus, with the same susceptibility pattern as the previous isolate; no other organism was identified. MRI of the feet was negative for osteomyelitis, and an abdominal CT scan revealed no pathologic lesions. The patient once again refused a transesophageal echocardiogram. He was treated with intravenous ceftriaxone and gentamicin for 10 days, the cellulitis improved, and repeat blood cultures were once again negative for any organism. He was discharged on a 2-week course of oral trimethoprim-sulfamethoxazole. The patient alleged compliance and seemed to be well over the next 6 weeks, but then he developed fevers up to 103°F, rigors, and a nonproductive cough with left-sided pleuritic chest pain. He presented to the clinic, where a chest radiograph revealed pneumonia with cavitation. A diagnosis of community-acquired pneumonia was made and the patient was readmitted to the hospital for the third time in 3 months. Physical examination revealed a disheveled male in no apparent distress, with a blood pressure of 122/64 mm Hg, heart rate of 104 beats per minute, regular respiratory rate of 24 per minute, and a temperature of 102.7°F. Findings included tenderness over the left lateral chest wall, rhonchi over the left upper lobe, a new, soft II/VI systolic murmur at the left lower sternal border, and limitation of motion of the right shoulder with no erythema, warmth, or effusion noted. There were no conjunctival petechiae, Roth spots, splinter hemorrhages, or Osler nodes. Neurologic examination was normal. The white blood count was 13,600/mm3, and hematocrit was 0.315. Arterial blood gas results were PaO2 77 mm Hg, PCO2 35 mm Hg, pH 7.51, and O2 saturation of 94% on room air. Chemistry profile and liver enzymes were within normal limits. Erythrocyte sedimentation rate was 75 mm/hour. The chest radiograph revealed an infiltrate with a 3- ⫻ 2-cm cavitation in the left upper pulmonary lobe consistent with a necrotizing pneumonia. A transthoracic echocardiogram revealed a new mobile echodensity on the tricuspid valve, consistent with vegetation, and grade 3/4 tricuspid regurgitation. Patient was initially treated with vancomycin and ticarcillin/clavulanic acid for presumed right-sided endocarditis and pneumonia. The antibiotic regimen was changed to ticarcillin/clavulanic acid plus gentamicin when blood cultures revealed Gram-negative bacilli. Final identification of sputum and blood culture isolates showed C diversus, with the same susceptibility pattern as in the two previous admissions. After an improvement in his clinical condition, resolution of pneumonia, and negative repeat blood cultures, the patient was discharged on oral ciprofloxacin for an additional 3 weeks of therapy. (Fig. 1).
he genus Citrobacter includes aerobic, Gramnegative bacilli that can be found in soil, food, and water and that are able to cause serious infections in humans involving the urinary, gastrointestinal and respiratory tracts and the central nervous system.1 Citrobacter species have also been reported as a rare cause of bacteremia and endocarditis in narcotic addicts.2 There are three species in the genus Citrobacter: C amalonaticus, C diversus, and C freundii. Here, we describe a case of tricuspid valve endocarditis in an intravenous drug user (IVDU) caused by Citrobacter diversus alone. Case Report A 51-year-old man was admitted to the hospital because of a 10-day history of fever, chills, right shoulder pain, and left-sided pleuritic chest pain. His past medical history was significant only for bilateral transmetatarsal amputations 20 years earlier because of frostbite. He reported a history of intravenous drug use over the past 20 years, unprotected heterosexual activities with several partners, and current use of alcohol, cocaine, and marijuana. Three months before presentation, he had been admitted with left shoulder pain and fevers up to 102.5° F. Purified protein derivative (tuberculin) skin test was normal and serum was negative for HIV. Cultures of both an aspirate of the shoulder joint and urine were negative for bacterial growth. However, blood cultures grew group G streptococci and Citrobacter diversus, sensitive to tobramycin, gentamicin, trimethoprim-sulfamethoxazole, ticarcillin, ofloxacin and cephalosporins. There was no heart murmur, and a transthoracic echocardiogram did not reveal vegetations or other abnormalities. The patient declined a transesophageal echocardiogram. After 8 days of intravenous antibiotic therapy with gentamicin, ceftriaxone, and vancomycin, repeated blood cultures were negative. The patient was
From the Division of Infectious Diseases (IT, IO, WED), Department of Medicine (GSC), University of Alabama at Birmingham, Birmingham, Alabama. Submitted May 10, 2000; accepted August 16, 2000. Correspondence: Dr. William E. Dismukes, Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, 1900 Univ. Blvd., 229 THT. Birmingham, AL 35294-0006.
408
December 2000 Volume 320 Number 6
Tellez et al
Figure 1. Clinical course during the patient’s hospitalizations. First admission: patient had left shoulder pain and fever. Blood cultures were positive for group G streptococci and C diversus. Second admission: patient presented with bilateral lower extremity cellulitis and fever. Blood cultures again grew C diversus. Third admission: patient presented with pneumonia, fever, and a heart murmur. Sputum and blood cultures were positive for C diversus. A transthoracic echocardiogram revealed a vegetation on the tricuspid valve. WBC, white blood count; BlCx, blood cultures; Cx, culture; Neg, negative; TTE, transthoracic echocardiogram; L, left; R, right; LE, lower extremity.
Discussion Right-sided valvular infective endocarditis is frequently a disease of IVDU. Bacterial endocarditis in this population has been estimated to be 1.5 to 20 per 1000 addicts per year.3,4 Several mechanisms have been proposed to explain the increased prevalence of right-sided endocarditis among IVDU.5 These include valvular endothelial injury, physiologic effects of injected substances, characteristics of the particular infective agent, and the host’s immune responses. Staphylococcus aureus has been the organism most commonly isolated in right-sided, addict-associated endocarditis, followed by streptococci (groups A, B, and G).6,7 Gram-negative organisms account for 4.8 to 7.5% of these cases; in this group, Pseudomonas aeruginosa predominates. C freundii and C diversus (formerly C THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES
koseri) have been described as rare causes of mitral and aortic valve endocarditis, respectively.8–9 Susceptibility patterns are different according to the Citrobacter species. For example, C diversus is usually sensitive to aminoglycoside drugs, trimethoprim-sulfamethoxazole, cephalothin, and, to a lesser degree, tetracycline.1 Our case is the first reported to date of an IVDU with tricuspid valve endocarditis caused by C diversus alone. Our patient probably acquired his Citrobacter infection while abusing drugs weeks to months before his first hospitalization. It is likely that the patient was not compliant while on oral antibiotic therapy. The findings of pleuritic chest pain, pulmonary infiltrate with cavitation, and left shoulder pain are common in IVDUs with endocarditis.10,11 By contrast, an indolent course with repeated admissions 409
Citrobacter diversus Endocarditis
for unexplained bacteremia in an IVDU should raise a high index of suspicion for right-sided endocarditis. Once the diagnosis is established, antibiotic treatment should continue for a minimum of at least 4 weeks, even in the absence of vegetation on a transthoracic or transesophageal echocardiogram. References 1. Lipsky BA, Hook ED III, Smith AA, et al. Citrobacter infections in humans: experience at the Seattle Veterans Administration Medical Center and a review of the literature. Rev Infect Dis 1980;2:746 – 60. 2. Crane LR, Levine DP, Zervos MJ, et al. Bacteremia in narcotic addicts at the Detroit Medical Center. I. Microbiology, epidemiology, risk factors and empiric therapy. Rev Infect Dis 1986;8:364 –73. 3. Levine DP, Crane LR, Zervos MJ. Bacteremia in narcotic addicts at the Detroit Medical Center. II. Infectious endocarditis: a prospective comparative study. Rev Infect Dis 1986; 8:374 –96.
410
4. Chan P, Ogilby ID, Segal B. Tricuspid valve endocarditis. Am Heart J 1989;117:1140 – 6. 5. Frontera JA, Gradon JD. Right-side endocarditis in injection drug users: review of proposed mechanisms of pathogenesis. Clin Infect Dis 2000;30:374 –9. 6. Chambers HF, Korzeniowski OM, Sande MA. Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts. Medicine 1983;62:170 –7. 7. Hecht SR, Berger M. Right-sided endocarditis in intravenous drug users. Ann Intern Med 1992;117:560 – 6. 8. Plantholt SJ, Trofa AF. Citrobacter freundii endocarditis in an intravenous drug abuser. South Med J.;1987;80: 1439 – 41. 9. MacCulloch D, Menzies R, Cornere BM. Endocarditis due to Citrobacter diversus developing resistance to cephalothin. N Z Med J 1977;85:182–3. 10. Cunha BA. Endocarditis in the narcotic addict. Infect Dis Clin Pract 1986;10:1– 8. 11. Robbins MJ, Soeiro R, Frishman WH. Right sided valvular endocarditis: etiology, diagnosis, and an approach to therapy. Am Heart J 1986;111:128 –35.
December 2000 Volume 320 Number 6