Infectious Diseases Conference

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Infectious Diseases Conference

• January 13th 2003
• Charles de Comarmond MD
• Infectious Diseases Fellow

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History of present illness

• 38 yr old WF with Hx of multiple sclerosis and
  multiple admissions for related problems.
• She was discharged from WFUBMC 12/24/02 after a 4
  day hospitalization for hyponatremia.
• Admitted 12/25/02 with fever, chills and left arm
  swelling.

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History of present illness

• Patient reports mild left arm swelling at the
  time of discharge and was recommended to apply
  warm compresses to the affected arm.
• At the time of discharge patient was afebrile.

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History of present illness

• Patient reports that she remarked rapidly
  worsening left arm swelling, redness and pain one
  day prior to admission. She also reported fever
  of 104F associated with nausea and vomiting.
• On presentation to the ED, patient febrile (Temp
  101F).

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History of present illness

• Doppler study of upper extremities negative for
  DVT.
• Started on empiric ABX in ED.
• Admitted to day hospital and develops shortness
  of breath and chest pain.

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Past medical Hx, FHx, SHx, ROS

• Multiple sclerosis
• Seizure disorder
• Pernicious anemia
• Chronic back syndrome
• Migraine headache
• Depression

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Medications

• Betaseron
• Ampicillin-sulbactam
• Vancomycin
• Tegretol
• Librium
• Paxil
• Risperidal
• Trazodone
• Vicodin
• Phenergan

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Past medical Hx, FHx, SHx, ROS

• FHx Non-contributory
• SHx 20 pack/year smoker, occasional ETOH
• ROS chronic low grade temp, repeated
  admission for hyponatremia

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Physical exam

• Vitals Tmax. 101.5 F, HR86, RR20, BP 111/79.
• Appeared comfortable at time of exam.
• Skin no rash or jaundice
• HEENT PERLA, ears, nose, mouth normal
• Neck supple

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Physical exam

• Chest Clear
• Heart S1S2 regular rate and rhythm
• Abdomen Soft, no hepatosplenomegaly
• Extremities Grossly erythematous swelling of the
  cubital fossa, with erythema extending to the
  palmar aspect of left wrist. No evidence of
  drainage.
• Neuro AAOx3

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Labs

• WBC 5.3 segs 84
• bands 5
• lymphs 7
• monos 4
• Hemoglobin 12.2 mg/dL
• MCV 102.8 FL
• Platelets 248

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Labs

• Na 130
• K 4.2
• Cl 9.2
• BUN 8
• Creatinine 0.8
• Glucose 107
• Calcium 8.4
• UA normal

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Labs

• 12/25/02 BC gram ve cocci (1 of 1)
• Cardiac echo
• Overall normal valvular appearance and function
  with mild mitral regurgitation and tricuspid
  regurgitation. No pericardial effusion.

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Differential diagnosis
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• Op note The cephalic vein was dissected out and
  was noted to be thrombosed. There was an abscess
  cavity right at the antecubital fossa. The vein
  was tied off distally, and the entire cephalic
  vein and a portion of the basilic vein were
  completely excised.
• Pathology Acute phlebitis with necrosis and
  organizing thrombus. There is focal necrosis of
  the intima. Neutrophils infiltrate the wall of
  the vessel.

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Follow-up cultures

• 12/25/02 BC (1 of 1) Staph. aureus
• 12/26/02 BC (1 of 4) Staph. aureus
• 12/28/02 BC (2 of 2) no growth
• 12/29/02 BC (2 of 2) Staph. Aureus
• All organisms displayed same susceptibility
  patterns.

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Differential Diagnosis

• Infectious
• Multiple abscesses Bacteremic patients may
  develop multiple lung abscesses, which are more
  common in dependent areas of the lungs. Typically
  the lesions are between 0.5 and 3 cm in diameter,
  round, and well-defined.
• Septic emboli Septic thrombophlebitis may
  generate septic emboli which produce multiple 0.5
  to 3 cm round or wedge-shaped nodules with a
  predilection for peripheral areas of the lower
  lobes Cavitation is common, usually producing
  thin-walled lesions. On CT, subpleural lesions
  can display a feeding vessel.

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Differential Diagnosis

• Fungi
• Histoplasmosis
• Coccidioidomycosis
• Aspergillosis
• Cryptococcus
• In these cases, the lesions tend to range from
  0.5 to 3 cm in diameter without a clear
  predilection for a specific area of the lungs

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Differential Diagnosis

• Neoplastic
• Metastatic solid organ malignancies
• the most common cause of multiple pulmonary
  nodules and account for 80 percent of such cases.
  
• The lesions are variable in size and location,
  with a proclivity for the better perfused lung
  bases
• The lesions are usually round with sharply
  demarcated borders
• Cavitation of metastatic lesions occurs in less
  than 5 percent of cases.

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Differential Diagnosis

• Non-Hodgkin's lymphoma These are more common in
  the lower lobes.
• Intrapulmonary lymphoma nodules usually originate
  from the bronchial-associated lymphoid tissue
  (BALT), and occasionally exhibit a halo of ground
  glass attenuation
• HIV Kaposi's sarcoma can present with multiple
  pulmonary nodules in a peribronchovascular
  distribution.
• The size of these nodules tends to exceed 1 cm at
  the time of diagnosis

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Differential Diagnosis

• Noninfectious
• Inflammatory conditions
• Wegener's granulomatosis Can produce multiple
  round, sharply or poorly demarcated lesions
  varying in size from 0.5 to 10 cm.
• Areas of consolidation may be associated with
  nodules, and cavitation occurs in slightly less
  than one-half of patients, generally producing a
  thick wall with an irregular inner lining
• Lymphomatoid granulomatosis
• Sarcoidosis

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Differential Diagnosis

• PULMONARY ARTERIOVENOUS MALFORMATIONS
• Present radiographically as either solitary or,
  in 30 percent of cases, multiple pulmonary
  nodules.
• Lesions are usually well-defined, round or oval
  opacities ranging from 1 to 5 cm in diameter
• The presence of a shunt fraction of gt5 percent
  when breathing 100 percent oxygen in the absence
  of an intracardiac shunt strongly favors the
  diagnosis of pulmonary arteriovenous
  malformations.

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Differential Diagnosis

• PNEUMOCONIOSES
• Coal workers' pneumoconiosis
• Silicosis
• May evolve to progressive massive fibrosis or
  conglomerate masses, yielding a radiographic
  appearance of multiple pulmonary nodules
• These may range in size from 1 to 10 cm and
  usually are located in the upper lobes
• Calcification and cavitation are unusual, but can
  occur and raise the possibility of superimposed
  tuberculosis.

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Thrombophlebitis

• Thrombophlebitis represents a spectrum of disease
  processes and includes
• Nonspecific, nonsuppurative thrombophlebitis or
  "bland phlebitis" manifested by pain, tenderness
  and redness over the vein course
• Nonsuppurative thrombophlebitis caused by
  infection of an intraluminal thrombus
• Suppurative thrombophlebitis with intraluminal
  purulent exudate, necrosis of the vein and
  periphlebitic abscess

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Suppurative superficial thrombophlebitis

• Suppurative thrombophlebitis is an inflammation
  of the vein wall due to the presence of
  microorganisms and is frequently associated with
  thrombosis and bacteremia.

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Suppurative superficial thrombophlebitis

• Suppurative thrombophlebitis may be classified
  into four forms
• superficial
• central (including pelvic)
• cavernous sinus
• infection of the portal vein (pyelophlebitis).
• Superficial suppurative thrombophlebitis has been
  steadily increasing in incidence since the
  introduction of the plastic intravenous cannula.

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Epidemiology

• In several large series of burned patients,
  suppurative thrombophlebitis developed in 4 to 8
  and increased in frequency if cutdowns were
  performed.
• Suppurative thrombophlebitis is also found in
  other hospitalized patients (especially those
  with cancer or those receiving steroid therapy).
• J Trauma. 19688256. N Engl J Med.
  19702821452. Arch Surg. 1970100399.

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Epidemiology

• During an 8-month period in Johannesburg,
  suppurative thrombophlebitis was estimated to
  represent a minimum incidence of 0.12 of all
  admissions.
• Pediatr Infect Dis J. 1987664-67.
• Data from the National Nosocomial Infection Study
  estimated the overall incidence of suppurative
  thrombophlebitis as 88 per 100,000 discharges,
  but this disease is under-reported.
• Hospital Infections. Boston Little, Brown
  1979433-442.

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Pathogenesis

• The risk of this complication is approximately 40
  times higher with plastic cannulas (8) than with
  steel or "scalp vein" cannulas (0.2).
• Development of suppurative thrombophlebitis is
  more common with usage of Polyethylene catheters
  gt Teflon gt Silastic material.

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Pathogenesis

• When examined by phlebography at the time of
  catheter withdrawal, 42 of catheters have sleeve
  thrombi, and another 8 reveal veno-occlusive
  thrombi.
• Ann Surg. 1981194779-783.
• When thrombosis and bacterial or fungal
  contamination or sepsis co-exist, suppurative
  thrombophlebitis may intervene.

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Pathogenesis

• The pathogenesis of suppurative thrombophlebitis
  is poorly understood. A thrombus may act as a
  nidus for local entrapment and colonization of
  bacteria that gain access to the site from
  another focus.
• The route of infection in superficial suppurative
  thrombophlebitis is associated with intravascular
  cannulas
• (1) migration from the skin between the catheter
  wall and perivascular tissue,
• (2) contamination of IV fluid,
• (3) contamination of the hub,
• (4) hematogenous dissemination from an infected
  focus elsewhere.

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Pathology

• There may be associated perivascular suppuration
  or hemorrhage and the vein lumen usually contains
  both pus and thrombus.
• Periphlebitic abscesses are not unusual and may
  be evident on physical examination.
• Microscopically, endothelial damage, fibrinoid
  necrosis, and thickening of the vein wall are
  evident.
• Microabscesses may be present in the vein wall or
  in the surrounding tissue.
• Gross thrombi frequently extend beyond the area
  of suppuration.

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Pathology

• In an autopsy series of peripheral suppurative
  thrombophlebitis in burned patients, extension of
  the clot into the great central veins was found
  in 18 of the cases.
• Metastatic abscess formation and septic pulmonary
  emboli with infarction are found in over 50 of
  the fatal cases.
• Pruitt BA, McManus WF, Kim SH, et al. Diagnosis
  and treatment of cannula-related intravenous
  sepsis in burn patients. Ann Surg. 1980191546.

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Microbiology

• S. aureus was the causative agent of 65 to 78 of
  the cases of superficial suppurative
  thrombophlebitis reported before 1968.
• In a review of 86 cases compiled from the
  literature reported since 1970, the organisms
  isolated were as follows
• Klebsiella-Enterobacter spp., in 34 cases
• S. aureus, in 15
• C. albicans, in 9
• E. coli, in 6
• Providencia spp., in 5
• Proteus spp., in 5
• S. epidermidis, in 4
• Serratia spp., in 3
• P. aeruginosa, in 3
• enterococci, in 2.
• Garrison RN, Richardson JD, Fry DE.
  Catheter-associated septic thrombophlebitis.
  South Med J. 198275917.

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• The pediatric infectious disease journal
  19971663-67

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South Med J. 198275917
The Ped Inf Dis J. 19971663-67
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Microbiology

• Study of the aerobic and anaerobic microbiologic
  characteristics of superficial suppurative
  thrombophlebitis.
• Retrospective review of microbiologic and
  clinical data at the Navy Hospital in Bethesda,
  Md.
• Sixty-one isolates, 36 aerobic and 25 anaerobic,
  were isolated from samples obtained from 42
  patients.
• Arch Surg 1996 Jan131(1)95-7

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Arch Surg 1996 Jan131(1)95-7
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Clinical Manifestations

• Superficial suppurative thrombophlebitis is often
  difficult to identify because local findings of
  inflammation may be absent.
• In 132 cases of superficial suppurative
  thrombophlebitis reported from the burn center at
  Fort Sam Houston, Texas, the distribution of
  affected vessels was as follows
• lower extremity (predominantly saphenous system),
  100
• upper extremity (predominantly antecubital
  fossa), 32
• jugular vein, 7
• iliac vein, 4.
• The mean duration of preceding venous cannulation
  was 4.81 days, and the latent interval from
  removal of the catheter to the development of
  symptoms ranged from 2 to 10 days.

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Clinical Manifestations

• Fever is present in over 70 of the cases, but
  rigors are rare.
• Local findings such as warmth, erythema,
  tenderness, swelling, or lymphangitis present in
  only 32 of the patients
• Bacteremia with signs of systemic sepsis found in
  84.
• Septic pulmonary emboli with secondary
  pneumonia--often the first diagnostic
  clue--occurred in 44.
• Pneumonia, sepsis, or metastatic abscess
  formation may be the only manifestation of this
  disease in two thirds of the cases.
• Late onset of pneumonia or sepsis in a burned
  patient demands the careful inspection of all
  previously cannulated veins, because untreated
  suppurative thrombophlebitis is associated with a
  high mortality.
• Fewer than 50 of the cases were diagnosed
  antemortem.
• Stein JM, Pruitt BA. Suppurative
  thrombophlebitis A lethal iatrogenic disease. N
  Engl J Med. 19702821452.

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Clinical Manifestations

• Most medical and postoperative patients develop
  the disorder in the upper extremities, and signs
  of local inflammation are more commonly present
  (94 in one series).
• Many of these patients are elderly with
  debilitating diseases and are often receiving
  antibiotics when superficial suppurative
  thrombophlebitis supervenes.
• Duration of intravenous catheterization is an
  important risk factor 68 of implicated cannulas
  had been left in place for at least 5 days.
• Baker CC, Peterson SR, Sheldon GF. Septic
  phlebitis A neglected disease. Am J Surg.
  197913897.

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Clinical Manifestations

• Suppurative thrombophlebitis of the thoracic
  central veins occurs in critically ill patients
  with central catheters in place, in those
  receiving TPN, or in patients after long-term
  cannulation with Broviac, Hickman, and other
  devices (Lemierre syndrome)
• Pelvic suppurative thrombophlebitis usually
  develops 1 to 2 weeks postpartum or
  postoperatively and is associated with high
  fever, chills, anorexia, nausea, vomiting,
  abdominal pain, and a protracted course.
• Approximately 80 of cases are unilateral on the
  right side, 14 are bilateral, and only 6 are
  unilateral and left-sided.
• Josey WE, Staggers SR. Heparin therapy in septic
  pelvic thrombophlebitis A study of 46 cases. Am
  J Obstet Gynecol. 1974120228.

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Diagnosis

• Bacteremia occurs in 80 to 90 of the cases of
  superficial suppurative thrombophlebitis.
• Gross pus within the vein lumen is found in about
  half of the cases, and this finding establishes a
  diagnosis of suppurative phlebitis.
• When infection of a venous catheter is suspected,
  it should be removed and cultured.
• The results, however, may be misleading, because
  even though bacteria will be isolated in up to
  60 of the cases, a positive culture does not
  correlate with inflammation.
• Maki DG, Weise CE, Sarafin HW. A semiquantitative
  culture method for identifying intravenous-cathete
  r-related infection. N Engl J Med. 19772961305.
  

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Diagnosis

• The chest x-ray film may reveal multiple septic
  pulmonary emboli.
• Ultrasonography is useful in delineating the
  location and extent of the thrombus and may also
  demonstrate the presence of a periuterine,
  adnexal or tuboovarian mass.
• CT reveals low attenuation with contrast
  enhancement in suppurative venous thrombosis and
  is very sensitive in the diagnosis of pelvic
  suppurative thrombophlebitis.
• MRI is sensitive and can differentiate fresh
  thrombus (1 week old) from organizing or subacute
  thrombus.
• 111 In-labeled leukocyte scanning, and
  laparoscopy is still undefined.
• Negative blood cultures do not exclude the
  diagnosis.

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Treatment

• Superficial suppurative thrombophlebitis is a
  lethal iatrogenic disease, and surgery is often
  necessary for cure.
• All authorities strongly endorse surgical
  excision as an integral part of treatment.
• Antibiotics should also be used in the treatment
  of this disease initial empirical treatment
  should cover Enterobacteriaceae or staphylococci
• The optimum duration of therapy is unknown and
  largely empirical.

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Treatment

• In a review of 24 patients,
• 14 were managed medically alone, and all died
  either directly from suppurative thrombophlebitis
  with persistent bacteremia or secondary to
  metastatic complications.
• 10 patients who underwent surgical exploration, 7
  survived, and only 1 of the 3 deaths was
  attributable to suppurative thrombophlebitis.
• Stein JM, Pruitt BA. Suppurative
  thrombophlebitis A lethal iatrogenic disease. N
  Engl J Med. 19702821452.

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Betaseron (Interferon beta-1b)

• Leukopenia occurred in 16 of patients (n124)
  receiving interferon beta-1b versus 5 in
  patients receiving placebo
• Product Information Betaseron(R), interferon
  beta-1b. Berlex Laboratories, Richmond, CA, (PI
  revised 10/1996) reviewed 06/2000.
• Lymphopenia and neutropenia occurred in 80 and
  17 of MS patients, respectively, receiving 8
  million units SC every other day in one large
  study
• Anon Placebo-controlled multicentre randomised
  trial of interferon beta-1b in treatment of
  secondary progressive multiple sclerosis. Lancet
  1998 352(9139)1491-1497.
• With subcutaneous therapy of MS, leukopenia
  rarely requires withdrawal of therapy white
  counts occasionally fall below 3000/mm(3) but
  tend to rebound and stabilize
• Lublin FD, Whitaker JN, Eidelman BH et al
  Management of patients receiving interferon
  beta-1b for multiple sclerosis report of a
  consensus conference. Neurology 1996 4612-18.

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Betaseron (Interferon beta-1b)

• Leukopenia is dose-related
• Anon Weekly Pharmacy Reports - The Green Sheet.
  1993a Vol 42, 35.
• Borden EC, Rinehart JJ, Storer BE et al
  Biological and clinical effects of
  interferon-beta-ser at two doses. J Interferon
  Res 1990 10559-570.
• Lethal capillary leak syndrome (CLS) was reported
  after the administration of one dose of
  interferon beta-1b. Approximately 80 hours
  post-dose, patient developed generalized
  peripheral edema, ascites, bilateral pleural
  effusions, and multiple organ failure leading to
  death. Serum samples collected approximately 3
  weeks prior to CLS showed a C1- inhibitor
  (C1-INH) deficiency.
• Schmidt S, Hertfelder HJ, von Spiegel T et al
  Lethal capillary leak syndrome after a single
  administration of interferon beta-1b. Neurology
  1999 53220-222.