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 (99 th 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
Prolonged (>3 weeks) febrile illness (temperature >38.3C) without an initially obvious etiology despite intensive evaluation and diagnostic testing (one week of study in the hospital). The following should have been performed and found unrevealing to establish FUO:

1. History and physical examination
2. CBC with differential and platelet count
3. Routine chemistries including liver enzymes and bilirubin
• If liver enzymes abnormal, hepatitis serologies
4. UA with microscopic examination
   • If UA is abnormal, a urine culture
5. Chest radiograph
   

Answer 3

1. Infection (24.5%)
   1. 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)
   2. Occult abscess: abdomen / pelvis / kidney / dental
      • predisposing factors: steroids, diabetes, immunosuppressants, valvular disease
   3. Osteomyelitis: vertebral / mandible
   4. (Culture negative) Bacterial endocarditis: 2-5% of cases of IE (infectious endocarditis) with 90% of cases having a positive TEE
2. Malignancy (14.5%)
   1. Advanced or aggressive Lymphomas (especially non-Hodgkin’s)
   2. Leukemia
   3. Renal Cell Carcinoma (presents with fever in 20% or cases)
   4. Hepatoma or tumors metastatic to the liver
3. Inflammatory / Collagen vascular diseases (23.5%)
   1. JRA / Stills disease: fever >39.5 for > 6 weeks with arthritis
   2. Giant cell arteritis : usually age >50 associated with headache, rapid vision loss, PMR, anemia and elevated ESR
4. Other (7.5%)
   1. 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
   2. Fictitious
   3. Pulmonary / deep venous embolism, hematoma
   4. Hyperthyroidism
5. No diagnosis (30%)
   

Answer 4

1. HISTORY AND PHYSICAL EXAMINATION

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

Answer 5

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

Answer 6

1. CD4 and viral load
2. HIV genotype (resistance test)
3. RPR
4. Hepatitis serologies
5. Toxoplasma titer
6. GC/Chlamydia test

Answer 7
 

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

Answer 8

1. History
   1. ROS with emphasis on usual sources of postoperative fever
   2. Review chart for pre-, intra-, or post- operative complications
   3. Review past medical history
      1. underlying diseases / surgery to evaluate cause of fever
   4. Review medications
   5. Review dates of placement and location of catheters
2. Physical examination
   1. Review fever curve
   2. Surgical site
   3. Skin evaluation for rash, ecchymosis, injection / catheter site infections
   4. Heart for new murmurs
   5. Lungs for signs of postoperative pneumonia
   6. Lower extremities for DVT
   7. Foley site
3. Laboratory: specific labs based upon physical assessment

Answer 9

• 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 10

• 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 11

• 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, Molds: Aspergillus, Zygomycetes, Scedosporium, Fusarium, others
• Viruses: HSV, VZV, CMV, EBV, enterovirus, RSV, influenza

Answer 12

An antipseudomonal β-lactams: Meropenem, imipenem,cefepeme, or ceftazidime.

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

Answer 13

1. Vancomycin the empiric use of vancomycin is only essential in the presence of:
   1. 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
   2. Hypotension or other signs of cardiovascular compromise

Answer 14

 Imipenem or meropenem would be most appropriate. Even though the MIC for ceftazidime is low, in vitro susceptibilities for cephalosporins for E cloacae are not reliable. Enterobacter and other gram negative rods (MYSPACE – morganella, yersinia, serratia, proteus, alcaligenes, citrobacter, enterobacter) have a chromosomally encoded beta-lactamase that is not expressed. However mutation to the expression phenotype may occur. Therapy with broad spectrum beta-lactam antibiotics (including ticarcillin or the third generation cephalosporins) with the exception of carbapenems selects for the resistant mutant. Therefore treatment with a carbapenem is recommended.

Answer 15

1. Reassess patient
2. Stop vancomycin if cultures are negative
3. Consider adding an antifungal agent
   1. candida coverage: fluconazole/micafungin
   2. mold coverage: Voriconazole/posaconazole/isovuconazole
      

Answer 16

The likelihood of cure of a catheter infection due to Staphylococcus aureus, Enteric gram negative bacilli, Pseudomonas aeruginosa, MDROs or yeast without removal of the catheter is less than 50%.Therefore the line should be removed without attempting to treat with the line in place. On the other hand if infection is due to coagulase negative staphylococcus,diphtheroids or streptococci, an attempt to treat with or without employing antibiotic lock therapy is reasonable.

Algorithm