Case #1 Answers:

Answer 1
In healthy individuals, the mean oral temperature is 36.8 + 0.4C (98.2 + 0.7F) with low levels in the morning and higher at 4-6PM. The maximum (99th percentile) normal oral temp at 6AM is 37.2 (98.9F) and the maximum oral temperature at 4PM is 37.7C (99.9F). Temperatures higher than these would be considered a fever. Rectal temperatures are 0.6C (1.0F) higher than oral readings (due to mouth breathing)

Answer 2
a. Infection (24.5%)
  i. Tuberculosis: most common infectious cause of FUO, usually extra-pulmonary or miliary with a negative PPD in up to 50% and sputum positive in 25% (diagnosed by BMA or LN biopsy)
  ii. Occult abscess: abdomen / pelvis / kidney / dental
       1. predisposing factors: steroids, diabetes, immunosuppressants, valvular disease
  iii. Osteomyelitis: vertebral / mandible
  iv. (Culture negative) Bacterial endocarditis: 2-5% of cases of IE (infectious endocarditis) with 90% of cases having a positive TEE
b. Malignancy (14.5%)
  i. Advanced or aggressive Lymphomas (especially non-Hodgkin’s)
  ii. Leukemia
  iii. Renal Cell Carcinoma (presents with fever in 20% or cases)
  iv. Hepatoma or tumors metastatic to the liver
c. Inflammatory / Collagen vascular diseases (23.5%)
  i. JRA / Stills disease: fever >39.5 for > 6 weeks with arthritis
  ii. Giant cell arteritis : usually age >50 associated with headache, rapid vision loss, PMR, anemia and elevated ESR
d. Other (7.5%)
  i. Drugs (can occur shortly after starting the drug to months or years later)
     1. Antibiotics: sulfa, penicillins, nitrofurantoin, antimalarials
     2. H1 and H2 blocking antihistamines
     3. Antiepileptic drugs (phenytoin and barbiturates)
     4. Iodides
     5. NSAIDS
     6. Antihypertensives (hydralazine, methyldopa)
     7. Antiarrhythmic drugs (quinine, procainamide)
     8. Antithyroid drugs
     9. Alcoholic hepatitis
  ii. Fictitious
  iii. Pulmonary / deep venous embolism, hematoma
  iv. Hyperthyroidism
e. No diagnosis (30%)

 

Answer 3
 

a. HISTORY AND PHYSICAL EXAMINATION
  i. Thorough history including:
     1. travel
     2. immunosuppression
     3. drug and toxin history including antimicrobials
         a. steroids or immunosuppressants may blunt fever
     4. localizing symptoms
         a. subtle changes in behavior: granulomatous meningitis
         b. jaw claudication: giant cell arteritis
         c. nocturia: prostatitis
         d. degree of fever, nature of fever curve, response to antipyretics
     5. social history
  ii. Physical examination
     1. thorough physical examination including genitals and skin

 

Answer 4
a. Above noted tests to rule out FUO
b. Specific tests based upon patients complaints or physical findings
  i. back pain: CT or MRI of the spine
  ii. new murmur: echocardiogram
  iii. subtle neurological findings: lumbar puncture / head CT or MRI
  iv. travel history
     1. malaria smear
     2. coccidiodomycosis, blastomycosis or histoplasma antigen
c. ESR, rheumatoid factor, ANA
d. LDH
e. PPD
f. HIV test in individuals with HIV related risk factors
g. Three routine blood cultures from different sites over a period of at least several hours without administering antibiotics
h. CT scan of the abdomen and pelvis to rule out occult abscess or abdominal lymphadenopathy
  i. May consider gallium scan or indium leukocyte scan
i. Biopsy
  i. Bone marrow: military TB, fungal infections
  ii. Lymph node: malignany or infection (TB, cat sctatch)
  iii. Liver: granulomatous hepatitis or sarcoid
  iv. Temporal artery: giant cell arteritis
  v. Pleural or pericardial: tuberculosis
 

Answer 5
a. CD4 and viral load
b. RPR
c. Hepatitis serologies
d. Toxoplasma titers
 

Answer 6
a. Inflammatory stimulus of surgery
  i. Occurs in the first few days after major surgery and resolves spontaneously
b. Surgical site infection
  i. Hyper-acute: clostridium perfringens or Group A Streptococcus
  ii. Most common source Staphylococcal from skin
     1. S. aureus: early onset
     2. S. epidermidis: later onset
  iii. Endogenous flora or the skin and bowel
  iv. Foreign body infection (graft, hardware, stent, valve…)
c. Nosocomial / Ventilator associated pneumonia
  i. Risk factors
     1. Aspiration
     2. presence of a NGT
d. Catheter related infection
e. Urinary tract infection / indwelling urethral catheter
f. Blood products
g. Drug fever
  i. malignant hyperthermia
  ii. antibiotics
  iii. anticonvulsants
  iv. antibiotic associated colitis
h. Deep venous thrombosis
i. Post operative ileus / ischemia due to hypotension
j. Other less common causes
  i. Community acquired infection brought into the hospital
 ii. Sinusitis due to presence of a NGT
  iii. Meningitis associated with neurosurgical procedures
  iv. Acalculous cholecystitis (AAA repair)
  v. Gout or pseudogout
  vi. Pancreatitis
  vii. Cardiovascular events
  viii. Thyroid storm
 

Answer 7
a. History
  i. ROS with emphasis of possible sources of postoperative fever
  ii. Review chart for pre-, intra-, or post- operative complications
  iii. Review past medical history
     1. underlying diseases / surgery to evaluate cause of fever
  iv. Review medications
  v. Review dates of placement and location of catheters
b. Physical examination
  i. Review fever curves
  ii. Surgical site
  iii. Skin evaluation for rash, echymosis, injection / catheter site infections
  iv. Heart of new murmurs
  v. Lungs for postoperative pneumonia
  vi. Lower extremities for DVT
  vii. Foley site and bag
c. Laboratory: specific labs based upon physical assessment
 

Answer 8

HEENT: mucositis (less common sinuses, dental)
Lungs: pneumonia, PE
Heart: SBE from central line (rare)
Abdomen: translocation of bacteria; typhlitis, antibiotic colitis, obstruction
Urinary tract: foley, obstruction by tumor
Skin: line site infections
 

Answer 9

Risk of occult infections increase when the ANC < 1,000 and substantially higher
if ANC is <500
Rapid decline in ANC
Prolonged duration of neutropenia (> 7 – 10 days)
Leukemia induction
Uncontrolled cancer
Comorbid illnesses requiring hospitalization
Immune defects associated with the underlying malignancy
 

Answer 10

Most infections arise from the patients endogenous flora
Gram Positives (approx. 51%)
Common: Coagulase-negative staphylococcus, Staphylococcus aureus
(MRSA), Streptococcus pneumoniae, Corynebacterium, Streptococci,
enterococci (VRE)
Less common: Bacillus, Listeria, Stomatococcus
Gram Negatives (approx. 40%)
Common: E. coli, Klebsiella, Pseudomonas, Enterobacter
Less common: Proteus, Haemophilus, Citrobacter, Serratia, Acinetobacter
Anaerobes (approx 3%): C. diff
Fungal: candida, Aspergillus, dimorphic fungi, Zygomycetes
Viruses: HSV, VZV, CMV, EBV, enterovirus, RSV, influenza
 

Answer 11

An antipseudomonal β-lactam (piperacillin) and pseudomonocidal aminoglycoside (gentamicin or tobramycin) combination is traditionally used, monotherapy with imipenem, meropenem, cefepeme, or ceftazidime are also be acceptable.

Oral therapy with ciprofloxacin plus amoxicillin-clavulinate my be considered in low risk adult patients)
 

Answer 12

a.     Vancomycin the empiric use of vancomycin is only essential in the presence of:

                                                    i.     Culture proven infection or clinical signs of infection (i.e. cellulitis, skin abscesses or IV catheter site infection) due to a resistant pathogen that is susceptible only to vancomycin

1.     MRSA or Pneumococcus

2.     Patients with quinolone prophylaxis

3.     Patients with intensive chemotherapy resulting in severe mucositis

                                                  ii.     Hypotension or other signs of cardiovascular compromise

The patient received empiric ticarcillin and tobramycin, the blood cultures grow Enterobacter cloacae, MIC are as follows:   ticarcillin >128, tobramycin >8, ceftazidime 2, imipenem 2, gentamicin 4, piperacillin >128, amikacin 4.

Answer 13

Imipenem or meropenem plus amikacin would be most appropriate. Even though the MIC for ceftazidime is low, in vitro susceptibilities for cephalosporins for E cloacae are not reliable. Also cefatizidime is known to trigger the production of β-lactamases, which destroy ceftazidime.

Answer 14

. Reassess patient
b. Stop vancomycin if cultures are negative
c. Consider adding an antifungal agent
i. Amphotericin B / Amphotericin B liposomal product
ii. Voriconazole
iii. Caspofungin
 

Answer 15

An Azole (fluconazole, itraconazole, voriconazole) or Caspofungin

Answer 16

a. If a catheter is the likely source of infection with resistant gram positive
organisms, gram negative organisms, fungal, and mycobacterial
organisms it is an indication to remove the catheter.
b. Inability to sterilize the blood stream with antimicrobials
c. Evidence of disseminated infection or endocarditis presumed or
suspected to be due to a central line infection