Bacteremia, vertebral diskitis, and osteomyelitis in a man with cirrhosis

A 51-year-old male presented to our emergency department with persistent, stabbing low back pain for 3 weeks. The pain, which was unrelieved with OTC acetaminophen, radiated “around the beltline” and down the left leg. The man reported that the pain had come on suddenly and associated it with shoveling snow a few days prior to onset. He had also experienced shaking chills and fever. Over the past few months, the patient had lost approximately 30 lb. His history was significant for alcoholism and tobacco abuse. A review of systems was negative for loss of bowel or bladder function, headache, numbness or weakness of the lower extremities, cough, shortness of breath, nausea, vomiting, diarrhea, or abdominal pain.

Vital signs were temperature, 102.3ºF; pulse rate, 82 beats per minute; respirations, 20 breaths per minute; BP, 106/51 mm Hg. The patient was a thin, ill-appearing man who looked slightly older than his stated age. His sclerae were mildly icteric. On auscultation, the heartbeat was regular; no murmurs, rubs, or gallops were heard. The lungs were clear and without wheezing, rales, or rhonchi. The abdomen was soft and nontender with slight hepatomegaly. Palpation of the back revealed point tenderness at the L3-5 level and decreased lumbar flexion with no gross anatomic abnormality. The extremities were neurologically intact with 5/5 strength bilaterally and no sensory deficits.

A WBC count was 11.9×103/µL; differential was 79% neutrophils, 16% lymphocytes, 4% monocytes, and 1% eosinophils. Hemoglobin was 12.4 g/dL; hematocrit, 35.6%; platelets, 288×103/µL. The ESR was 98 mm/h. The metabolic panel included BUN, 11 mg/dL; creatinine, 0.6 mg/dL; AST, 125 U/L; ALT, 125 U/L; alkaline phosphatase, 128 U/L; albumin, 3.0 g/dL; total bilirubin, 1.3 mg/dL; and total protein, 8.7 g/dL. Results of a hepatitis panel were positive for previous exposure to hepatitis A virus and for hepatitis C virus antibodies, but negative for hepatitis B virus. HIV screening and urinalysis were negative. Two sets of blood cultures were obtained.

Radiography of the lumbosacral spine showed degenerative narrowing of the disk spaces from L3 through S1 and degenerative facet changes at L4-5 and L5-S1, with no destructive lesions evident. CT of the chest showed a nodule measuring 1 cm×6 mm in the upper lobe of the right lung. Scattered bilateral calcified pulmonary parenchymal granulomas were seen. A 2.1×1.7-cm right hilar lymph node was visible. CT of the abdomen demonstrated abnormal enhancement in the right lobe of the liver near the dome. Numerous retroperitoneal lymph nodes were seen; none was pathologically enlarged. The pancreas, spleen, adrenals, and kidneys were unremarkable. CT of the lumbar spine showed lytic lesions of the L3 and L4 vertebral bodies that were not visualized on a previous CT of the spine. Lucent lesions within the L3 and L4 vertebral bodies posteriorly adjacent to the L3-4 interspace raised the possibility of a destructive process, and osteomyelitis was considered in the differential.

MRI with and without gadolinium revealed diskitis at L3-4 with osteomyelitis of the L3 and L4 vertebral bodies. Paraspinal soft-tissue involvement extended around the left side of the L3 and L4 vertebral bodies. Edema was noted in the left psoas muscle; there were no signs of abscess. Abnormal marrow signal within the L5-S1 vertebral bodies was also observed (see Figure 1).

Following this evaluation, consults were requested from the neurosurgery and infectious disease services. Differential diagnoses included bacterial infection and malignancy. Initial empiric treatment included ampicillin, 2 g IV every 6 hours, and vancomycin, 1 g IV every 12 hours. At the time of the infectious disease consultation, the patient's fever, chills, and rigors were unabated, and the antibiotics were adjusted to include cefepime, 2 g IV every 12 hours; the ampicillin was discontinued. Initial blood cultures were reported 48 hours after admission as two of two sets positive for gram-negative coccobacilli (likely a Haemophilus species). When the patient continued to have fevers and chills, the cefepime dosage was increased to 2 g IV every 8 hours. On the fourth day of admission, blood cultures were finalized and reported as ampicillin-sensitive Haemophilus aphrophilus. The vancomycin was discontinued. The patient's fever declined. Although culture of a specimen obtained on CT-guided biopsy from the L4 vertebral body was negative, histopathology results were compatible with osteomyelitis.

Additional studies were performed. A two-dimensional echocardiogram was negative for vegetation. Follow-up of the abnormal enhancement of the right lobe of the liver included MRI, which showed a poorly enhancing mass, raising the possibility of hepatocellular carcinoma. Hepatomegaly, fatty infiltration, and a component of cirrhosis were noted. The patient was scheduled for a liver biopsy to evaluate for possible hepatocellular carcinoma. Histopathologic results of that study showed active cirrhosis of the liver without malignancy. Our patient was treated first with 3 weeks of IV ampicillin. He was later switched to oral trimethoprim-sulfamethoxazole for an additional 10 weeks.

DISCUSSION

Haemophilus species comprise aerobic and facultatively anaerobic gram-negative rods or coccobacilli. The organisms are small, pleomorphic, and nonmotile and do not form spores. Two accessory growth factors (X and V) are important criteria for defining Haemophilus species. In addition, growth can be enhanced in a 5% to 10% carbon dioxide-enriched atmosphere. H aphrophilus requires factor X growth factor and is carbon dioxide-dependent. Of the eight species of Haemophilus, H influenzae is the major human pathogen, with H influenzae type b (Hib) responsible for the majority of invasive infections associated with this species. Other species of Haemophilus responsible for human disease include H ducreyi, the causative agent of chancroid; and H aphrophilus, H paraphrophilus, and H parainfluenzae, which are occasionally implicated in brain and liver abscesses and in infective endocarditis. (Haemophilus species are included along with Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae in the group of bacteria known to cause endocarditis and identified as HACEK).1,2

Haemophilus organisms colonize the mucous membranes of humans, and therefore the pathogenicity of these organisms is thought to be low, with the most common illness being confined to the upper respiratory tract.2 However, in a small number of case reports, serious infections, including osteomyelitis, brain abscess, bacteremia, endocarditis, meningitis, and septic arthritis, have been caused by other Haemophilus species, ie, H aphrophilus.1,3

The most recently published retrospective study to include all invasive H aphrophilus infections identified 20 cases through a MEDLINE search and eight cases in the researchers' own facility from 1990-2003.4 Most of the cases were bone and joint infections, including osteomyelitis, diskitis, epidural abscess, spondylodiskitis, septic arthritis, and prevertebral infection totaling nine cases (32%). Of note, four of the nine bone and joint infections were diagnosed with blood cultures along with clinical correlation; the other five cases were diagnosed with cultures from the affected area. Vertebral osteomyelitis/diskitis was diagnosed in four cases, two of which occurred at the L4-5 vertebral level and one each at the T11-12 and C4-7 level.4 This retrospective study led by Huang, in addition to a previous case report and review by Colson and colleagues, documents 16 cases of vertebral osteomyelitis caused by H aphrophilus. To our knowledge, the case presented here is the 17th case of vertebral osteomyelitis caused by H aphrophilus.4,5

One patient in particular was found to have liver cirrhosis as an underlying factor associated with H aphrophilus vertebral osteomyelitis. In patients with underlying cirrhoses and bacteremia, the problem is thought to be inefficient clearing of bacteria by the reticuloendothelial system.6 The combination of liver cirrhosis and acute back injury experienced by our patient while shoveling snow may have predisposed him to a bacterial infection. That infection in turn seeded injured tissues of the back and caused vertebral osteomyelitis more easily than might be expected because of a disruption of local factors providing immunity. The research also reports other underlying diseases thought to be associated with acquiring H aphrophilus vertebral osteomyelitis, including diabetes mellitus, sciatica, and polyarthritis.6 Not surprisingly, recent dental procedures have been implicated as a predisposing risk factor in many cases.4 No such history was revealed in our patient.

Medications to which H aphrophilus has been reported susceptible include beta-lactam antibiotics, penicillin, ampicillin, trimethoprim-sulfamethoxazole, and cephalosporins; however, resistance to ampicillin and to some second- and third-generation cephalosporins (cefuroxime, ceftazidime, and cefotaxime) has emerged.5 Studies have shown ciprofloxacin to be an effective oral alternative.7 According to the case reports, duration of treatment for vertebral osteomyelitis due to H aphrophilus ranges from 4 to 27 weeks, with a mean duration of 10 weeks of antibiotic treatment.5 JAAPA

Ryann Morrison is a PA in infectious diseases at Lehigh Valley Hospital in Allentown, Pennsylvania. Jaan Naktin is an infectious disease physician at Lehigh Valley Hospital. The authors have indicated no relationships to disclose relating to the content of this article.

Acetaminophen
Ampicillin (Unasyn, generics)
Cefepime (Maxipime, generics)
Cefotaxime (Claforan, generics)
Ceftazidime (Fortaz, Tazicef, generics)
Cefuroxime (Zinacef, generics)
Ciprofloxacin (Cipro, generics)
Penicillin
Trimethoprim-sulfamethoxazole (Bactrim, Septra, generics)
Vancomycin

REFERENCES

1. Cohen J, Armstrong D. Infectious Diseases. 1st ed. Philadelphia, PA: Mosby; 1999.

2. Mandell GL, Bennett JE, Dolin R. Principles and Practice of Infectious Diseases. 6th ed. Philadelphia, PA: Churchill Livingstone; 2005.

3. Cecil RL, Goldman L, Bennett JC. Cecil Textbook of Medicine. 22nd ed. Philadelphia, PA: W. B. Saunders Company; 2004.

4. Huang ST, Lee HC, Lee NY, et al. Clinical characteristics of invasive Haemophilus aphrophilus infections. J Microbiol Immunol Infect. 2005;38(4):271-276.

5. Colson P, La Scola B, Champsaur P. Vertebral infections caused by Haemophilus aphrophilus: case report and review. Clin Microbiol Infect. 2001;7(3):107-113.

6. Hung CC, Hsueh PR, Chen YC, et al. Haemophilus aphrophilus bacteraemia complicated with vertebral osteomyelitis and spinal epidural abscess in a patient with liver cirrhosis. J Infect. 1997;35(3):304-308.

7. O'Driscoll JC, Keene GS, Weinbren MJ, et al. Haemophilus aphrophilus discitis and vertebral osteomyelitis. Scand J Infect Dis. 1995;27(3):291-293.