Infectious Diseases
Denise Marciano, M.D., Ph.D.
Michael Shiloh, M.D., Ph.D.
Meg D. Newman, M.D.
1. For antibiotic recommendations, refer to your local hospital’s guidelines or use the Sanford Guide to Antimicrobial Therapy (or similar resource).
2. Obtain blood cultures before starting antibiotics. It’s acceptable to start broad coverage (e.g. Zosyn®) while waiting for culture results, but consider which pathogens are likely given the clinical scenario and tailor your regimen in an appropriate fashion.
3. If your patient continues to spike through antibiotics, review your regimen and look for gaps in coverage. These may include (but are not limited to) fungi, atypical bacteria, resistant organisms (e.g. MRSA), organisms that occasionally require double coverage (e.g. Pseudomonas). Also consider hidden abscesses, drug fever and other non-infectious causes of fever. See also Infectious Diseases: Fever of unknown origin.
See Pulmonary: Community-acquired pneumonia.
See Renal: Urinary tract infection.
See Rheumatology: Septic arthritis.
1. Types: osteomyelitis can develop after bacteremia (hematogenous osteomyelitis) or from a contigous infection.
· Hematogenous osteomyelitis: primarily in children, IVDU, and the elderly. Adults generally present with vague complaints, although fever, chills, and edema and erythema over the bone are occasionally seen. S. aureus is most common. In IVDU consider Serratia, Candida, and Psuedomonas aeruginosa.
· Contiguous-focus osteomyelitis: most prevalent. occurs after injury, procedure, or extension from a soft tissue infection (e.g. decubitus ulcer). Infection usually occurs within 1 month after inoculation of the organism. Patient presents with low fevers, pain and drainage. In contrast to hematogenous osteomyelitis, mixed infections are common. S. aureus is most prevalent. Gram negative bacilli and anaerobic organisms are also common.
· Contiguous-focus osteomyelitis with vascular insufficiency (e.g. diabetes mellitus): almost exclusively in the feet. Onset is insidious and cellulitis may be minimal. Concurrent peripheral neuropathy may mute pain. Mixed infections are frequent. The most common organisms are staph, strep, enterococcus, Gram negative bacilli, and anaerobes.
· Vertebral osteomyelitis: usually hematogenous in origin. Localized pain and tenderness of the bone segment present in > 90% of patients. Fever and leukocytosis absent in 50%. Posterior extension may lead to epidural and subdural abscesses or meningitis. Extension anteriorly may lead to paravertebral, retrovertebral, mediastinal, subphrenic, or retroperitoneal abscesses. In the normal host, S. aureus is most common. In IVDU, Pseudomonas aeruginosa is most common. In additional to spinal vertebrae, the pubis symphisis, SC and SI joints are often involved sites.
2. Diagnosis:
· If you can probe down to bone on physical exam, the patient has osteomyelitis.
· Plain films may be normal early in the course of osteomyelitis, and an MRI or radionuclide bone scan may be necessary to make the diagnosis. MRI (if readily available) is the preferred modality because soft tissue involvement can also be observed.
· A positive blood culture or isolation of organisms by bone aspiration/biopsy is necessary for antibiotic selection. Note: contigous-focus and vertebral osteomyelitis will generally have sterile blood cultures and will require tissue for diagnosis. Don’t forget to consider fungi and acid-fast bacilli, especially with insidious onset of symptoms and negative cultures.
3. Treatment:
Lew DP, Waldvogel FA. Osteomyelitis. N Engl J Med. 1997 Apr 3;336(14):999-1007.
1. Standard fever workup: blood cultures x 3; separate 1 set of cultures by at least 1 hour (95–99% sensitive for endocarditis, 2 cultures is ~85-90% sensitive for endocarditis), urinalysis with urine culture, and CXR.
2. Careful skin exam for abscess, cellulitis and peripheral stigmata of endocarditis (indicating left sided valvular disease).
3. Palpate bones, especially spine for osteomyelitis and epidural abscess.
4. Pelvic exam in women to rule out pelvic inflammatory disease (PID) as a source of fever.
5. ECG on arrival and until endocarditis is ruled out to assess for PR interval prolongation, which indicates an aortic valve ring abscess.
6. Get an echocardiogram if a new murmur is present, if the patient is hemodynamically unstable, if there is PR prolongation, if there are persistently positive blood cultures, or if there is no response to therapy. Transesophageal echocardiogram (TEE) preferred in suspected left-sided endocarditis.
7. Empiric treatment for endocarditis in IVDU patients: vancomycin 15 mg/kg IV q12h (not to exceed 2 g/day) and gentamicin 1 mg/kg IV q8h.
8. Shooters with a fever should be admitted to the hospital. If you find no source of infection and your clinical suspicion is low, it is acceptable to observe the patient in the hospital without antibiotics. If the patient defervesces quickly off antibiotics, it may not be necessary to wait 48 hours for culture results prior to discharge. The protocol used at the San Francisco General Hospital is that patients may be discharged if at 24 hours, they are without fever, no antibiotics were started, and cultures are negative. Remember to try to obtain a contact number for the patient in case you have to follow up on any positive cultures.
1. Diagnosis rests on the modified Duke Criteria. In order to diagnose infectious endocarditis (IE), your patients needs to meet 2 major, 1 major + 3 minor, or 5 minor criteria.
2. Major Criteria:
- Two positive BCx for organisms typically causing IE (S. viridans, S. bovis, HACEK organisms, S. aureus, or Enterococcus) in the absence of other sources for infection.
- Microorganisms consistent with IE from persistently positive BCX. At least two positive BCx >12 hours apart, or at least 3 of 4 positive BCx.
· Positive echocardiogram:
- Oscillating intracardiac mass on valve or foreign body, or in path of regurgitant jets
- Abscess
- Partial dehiscence of prosthetic valve
- New valvular regurgitation (worsening or changing of previously existing murmur not adequate)
3. Minor Criteria:
4. Identified risk factors for endocarditis include prosthetic valve, previous endocarditis, IVDU, structural heart disease (e.g. sequelae of rheumatic heart disease, calcified or stenotic valves, MV prolapse, ventral septal defect), poor dental hygiene, long term hemodialysis, and DM.
5. Clinical manifestations are protean. Most have constitutional symptoms suggesting infection or chronic illness. Fever may be absent in 5% of patients. 85% have heart murmurs, but only 5-10% have a “changing murmur”. In some, initial manifestations may be from systemic embolization, presenting as stroke, splenic pain, visual loss, or loss of limb perfusion. Right-sided endocarditis may present with pulmonary embolus, pneumonia, or empyema. Cardiac involvement may present as CHF or conduction abnormalities. Renal involvement may be from abscess, infarction, or glomerulonephritis.
6. Skin manifestations include:
· Petechiae – on conjunctiva, palate, buccal mucosa
· Splinter hemorrhage – subungual linear streaks
· Roth spots – oval, pale retinal lesions surrounded by hemorrhage
· Osler nodes – small tender nodules on fingers or toes
· Janeway lesions – small, nodular, painless hemorrhages on palms or soles
7. The bacteremia is continuous and low grade. Two blood cultures are positive > 90% of the time. When blood cultures are negative, consider fungi (positive BCx in ~50%), slow-growing organisms (HACEK) and organisms requiring special growth media (e.g. Legionella, Bartonella). Repeat BCx one week after treatment is initiated because persistent bacteremia may indicate complications.
8. Identify potential sources of bacteremia that led to endocardial infection.
9. In native valve endocarditis, the sensitivity of TTE and TEE are ~70% and 90% respectively. Specificity is ~99% for both. The sensitivity of TTE is much lower (15-30%) in prosthetic valve infections. TTE may be inadequate with obesity or COPD.
10. Obtain ECGs to assess for PR prolongation due to perivalvular abscess.
11. Common pathogens in non-IVDU patient with native valve: Strep. viridans (60%), Staph. aureus (20%), Enterococci (5-10%), and coagulase-negative staphylococci. HACEK organisms (haemophilus, actinobacillus, cardiobacterium, eikenella, kingella) are also common.
12. Common pathogens in IVDU patient with native valve: Staph. aureus (60% of all cases and 80-90% of cases involving tricuspid valve) and unusual gram-negative bacilli and fungi are more common.
13. Common pathogens in patients with prosthetic valve: Coagulase positive and negative Staph, gram-negative organisms and fungi if valve is new (< 2 months). After 2 months, pathogens similar to native valve except more coagulase negative Staph.
14. The prevalence of endocarditis among patients with Staph aureus bacteremia is variable (13-25%). Factors associated with increased risk of IE include community acquisition, absence of a primary focus, presence of embolic disease, and fever or bacteremia > 3 days after catheter removal.
15. Treatment includes 4-6 weeks of antibiotics for left-sided endocarditis, 2 weeks for purely right-sided Staph aureus endocarditis. Some indications for surgery include fungal or Pseudomonas aeruginosa infection, valvular destruction, CHF, papillary muscle rupture, repeated large cerebral or coronary embolization, and persistent bacteremia.
16. After treatment, don’t forget prophylactic antibiotics before dental, GI or GU procedures. See Medical consultation: Prophylaxis for bacterial endocarditis.
Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific
echocardiographic findings. Duke Endocarditis Service. Am J Med. 1994 Mar;96(3):200-9.
Mylonakis E, Calderwood SB. Infective endocarditis in adults. N Engl J Med 2001; 345:1318-30.
1. The classic presentation of meningitis is fever, neck stiffness, and altered mental status. In adult patients, the absence of all 3 signs virtually eliminates the diagnosis of meningitis. If the patient has fever and headache, the “jolt” sign can be useful. If you take the patient’s head and “jolt” it (carefully) from side to side and there is no pain, this rules out meningitis (100% sensitivity when there is a positive “jolt” sign). The bottom line: since meningitis is such a serious diagnosis, your best bet is to simply proceed to lumbar puncture in the high risk patient in order to rule it out.
2. Lumbar puncture (LP) is the diagnostic test of choice.
· See also Procedures: Lumbar puncture.
· When do you need to get a CT prior to the lumbar puncture? proceed to head CT prior to LP if any of the following are present at baseline:
- Age > 60 years
- Immunocompromised
- History of CNS disease
- History of seizure within one week prior to presentation
- Any of the following neurologic abnormalities: an abnormal level of consciousness, an inability to answer two consecutive questions correctly or to follow two consecutive commands, gaze palsy, abnormal visual fields, facial palsy, arm drift, leg drift, or abnormal language (e.g., aphasia)
3. Contraindications: remember, DON’T DELAY ANTIBIOTICS even if you must delay the tap!
· Infection at LP site.
· Severe thrombocytopenia (platelets <30–50) or bleeding diathesis.
· Mass lesion suspected (e.g. brain abscess, tumor, subdural hematoma, intracranial hemorrhage) on the basis of immunosuppression, papilledema, coma, recent seizure or focal neurologic deficit. In this case, do CT or MRI first (see above).
· If imaging is indicated, obtain blood cultures, start empiric therapy and do LP immediately after imaging if no lesion is observed.
· Note that herniation following LP is rare even in patients with a documented mass lesion.
4. Tests to order:
· Tube 1: cell count and differential, tube 2: total protein and glucose, tube 3: culture and gram stain, and tube 4: cell count and differential (note: this may vary at individual hospitals).
· Depending on the clinical situation, may also order: cytology, VDRL, AFB stain/culture (often requires lab medicine approval), fungal stain and cultures (often require lab medicine approval), Cryptococcal antigen (CrAg), oligoclonal bands, MBP, Lyme titers, HSV PCR.
5. Interpretation of results (general guidelines – use your common and clinical sense):
· Note: > 99% certainty of bacterial meningitis if any of the following:
- CSF glucose < 34 mg/dl
- CSF/blood glucose ratio < 0.22
- CSF protein > 220 mg/dl
- > 2000 CSF WBC’s
- > 1180 CSF neutrophills
· Common pathogens:
- 18-50 years old: S. pneumoniae, N. meningitis, Listeria monocytogenes (unlikely if immunocompetent)
- >50 years old or with impaired cellular immunity: S. pneumoniae, Listeria, and gram negative bacilli. (N. meningitis is uncommon).
- AIDS: Cryptococcus, bacterial meningitis, Herpes, Coccidioides. See also ID/AIDS: AIDS and altered mental status.
- Post-surgical or post-traumatic: S. aureus, pseudomonas, coliforms, S. pneumoniae.
· Empiric bacterial meningitis treatment – (doses for adults with normal renal function)
- Ceftriaxone 2 g IV q12h + Vancomycin 1g (15 mg/kg) IV q12h (± Ampicillin 2 g IV q4 hours if Listeriais suspected).
- Adults with severely impaired mental status, documented cerebral edema, or markedly elevated ICP (high opening pressure or 6th nerve palsy) may benefit from adjunctive dexamethasone. Steroids decrease the CSF penetration of vanco, so do not use together.
· Remember: nosocomial meningitis is extremely rare in non-surgical patients.
Hasbun R, Abrahams J, Jekel J, Quagliarello VJ. Computed tomography of the head before lumbar puncture in adults with suspected meningitis. N Engl J Med. 2001 Dec 13;345(24):1727-33.
Attia J, Hatala R, Cook DJ, Wong JG. The rational clinical examination. Does this adult patient have acute
meningitis? JAMA. 1999 Jul 14;282(2):175-81.
|
Condition |
Appearance |
Glucose (mg/dl) |
Protein (mg/dl) |
Cell Count |
Differential |
Pressure(cm H2O) |
|
Normal |
Clear |
50–75% serum |
<50 |
<5 |
100% lymph |
5–20 |
|
Hemorrhage |
Bloody or xantho |
N or D |
I but <1000 |
RBC and WBC |
Same as blood |
Usually I |
|
Bacterial meningitis |
Cloudy or purulent |
< 40% serum |
45–500 |
100–100K |
>80% PMN |
Usually I |
|
Fungal meningitis |
Clear or cloudy |
20–40 |
25–500 |
25–1000 |
Inc mono and lymph |
N or I |
|
Aseptic/viral meningitis |
Clear or cloudy |
N or D |
50–200 |
25-2000 |
Inc mono and PMN early, then lymph |
N or I |
|
TB meningitis |
Cloudy |
<40 |
100–2000 |
50–500 |
Mostly lymph, some PMN |
Usually I |
|
Herpes encephalitis |
Bloody or xantho |
N or D |
50–100 |
20–500 |
Mostly lymph |
N or I |
|
Neoplasm |
Clear or xantho |
40–80 |
50–1000 |
<100 |
Mostly lymph |
Usually I |
|
Guillain– Barré |
Clear or cloudy |
N |
slight I |
<100 |
Mostly lymph |
N |
|
Neurosyphilis |
Clear or cloudy |
N |
40–200 |
200–500 |
Mostly lymph & mono |
N or I |
Abbreviations: N – normal; D – decreased; I – increased
1. The differential diagnosis includes the following:
|
Parenchymal |
Meningeal |
Other |
|
Toxoplasma |
Cryptococcus |
Metabolic |
|
CNS lymphoma |
Bacterial |
CVA |
|
PML |
Syphilis |
Drugs |
|
HSV encephalitis |
TB meningitis |
Systemic infection |
|
AIDS dementia |
Lymphoma |
Psychiatric |
Less common: bacterial abscess, tuberculoma, fungus (histo, cocci), CMV. Ideally, save an extra tube of CSF whenever possible in case extra PCR studies are desired for CMV, HSV, or TB.
2. Initial work-up should include a standard delirium evaluation (see Neurology: Altered mental status) plus the following:
· Brain imaging: MRI more sensitive for toxoplasmosis, lymphoma, AIDS dementia complex (ADC), PML, HSV, and meningeal enhancement, but get CT if you can’t get MRI in 12–24 hours or for pre–LP screen.
· LP: opening pressure, glucose, protein, cell count, CSF CrAg, VDRL. Also send serum CrAg and VDRL as well. Even if no cells are present, send cultures: bacterial, fungal, and cytology; in the worst cases of crypto, there are often < 5 WBCs because of poor inflammatory response. If high clinical suspicion, send AFB and viral cultures.
- Lymphocytosis: Crypto, TB, syphilis, fungal, viral, lymphoma
- Neutrophils: bacterial, CMV polyradiculopathy
- Low glucose: bacterial, TB, fungal, syphilis, lymphoma meningitis
- High protein: any of above
- RBCs: subarachnoid bleed, HSV or traumatic tap
3. Specific treatment:
· Ring–enhancing lesions: toxoplasmosis versus lymphoma.
- If serum toxoplasmosis IgG positive and no TMP/SMX prophylaxis, treat empirically for toxoplasmosis. If the lesion is very suspicious for lymphoma pursue biopsy while beginning treatment for toxoplasmosis. This consists of pyrimethamine 200 mg on day 1, then 100 mg po qd plus sulfadiazine (1.5 grams q6 hours) or clindamycin (600 mg po or IV q 8 hours). Rescan within 7 days. If no improvement clinically and radiologically, patient will need biopsy.
- Less than 5% of all cases of reactivation toxoplasmosis occur in the absence of IgG positivity.
- If serum toxoplasmosis IgG negative, or patient taking TMP/SMX, single lesion on MRI, or lesion crossing midline, consider early stereotactic biopsy. This usually requires strong advocacy for your patient.
- If confirmed lymphoma, consult oncology. IV chemotherapy is now being utilized along with HAART.
· Cryptococcus:
- Low risk patient (normal mental status, no headache, no nausea/vomiting, normal opening pressure): fluconazole 400 mg po qd. That being said, 99% of inpatients with cryptococcal meningitis require 14 days of IV Amphotericin.
- High risk patient (includes those with any of the following: altered mental status, nausea/vomiting, headache, elevated opening pressure, CSF WBCs < 20, or CSF CrAg > 1:1024): Ampho 0.75 mg/kg IV qd plus flucytosine 25 mg/kg IV q 6 hours,both for 14 days. When using amphotericin, give pre- and post-hydration with 500 cc NS. If creatinine is rising increase to 1 liter hydration pre and post. Avoid other nephrotoxic agents, and watch for significant K+ and Mg++ wasting. In patients with normal renal function, begin amphotericin with 20 mEq PO bid of KCl and Mg 500 mg PO q day. A renal tubular acidosis (RTA) will inevitably develop with Amphotericin. Hydrocortisone is only needed (as 25 mg in the bag of amphotericin) if patients continue to have rigors after day 3 or 4 that don't respond well to morphine. Morphine is just as effective as meperedine (Demerol®) for rigors.
· Neurosyphilis (CSF VDRL positive or serum VDRL positive with CSF lymphocytosis and high protein): penicillin G 2-4 million units IV q 4 hours x 10 days.
· Cerebral edema or mass effect (from toxoplasmosis or lymphoma): dexamethasone 4 mg IV q6 hours. If herniation, use mannitol 1.5-2.0 g/kg IV.
· Tuberculosis (lymphocytosis, low glucose, high protein, or AFB): isoniazide, rifampin, ethambutol, pyrazinamide, and dexamethasone.
· PML or AIDS dementia complex (ADC): HAART is the treatment of choice. Contact your local infectious disease or HIV specialist for advice on initial or salvage regimens.
Price RW. Neurological complications of HIV infection. Lancet. 1996 Aug 17;348(9025):445-52.
1. Differential diagnosis includes bacterial pneumonia, TB, PCP, Kaposi’s sarcoma, Coccidioides immitis, histoplasmosis, cryptococcus, COPD and other pulmonary diseases.
2. Initial work-up includes chest x–ray (rule out infiltrates, pneumothorax), ABG, ECG, basic labs, LDH (elevated LDH is very sensitive but not specific for PCP), blood cultures, sputum Gram stain and culture.
3. Bacterial pneumonia is the most frequent HIV-associated pulmonary disease reported. Note that there is an increased incidence of bacteremia, especially by S. pneumonia.
4. Suspect PCP with a subacute onset, fever, non-productive cough and dyspnea. The CXR classically shows bilateral interstitial opacities, but can present as anything. 10-20% will have a normal CXR. A pleural effusion or hilar lymphadenopathy on chest imaging may be present but should never be attributed to PCP. Consider TB, lymphoma, KS and fungal disease.
5. 95% of patients with PCP have CD4 < 200 but PCP can occur in CD4 > 200 if the patient is splenectomized, pregnant, or postpartum.
6. Obtain induced sputum for PCP if consistent with clinical presentation. Remember to make the patient NPO after midnight and submit forms to respiratory therapy.
7. Strongly consider placing patient on respiratory precautions to rule-out TB.
8. Consider empiric treatment for PCP. TMP/SMX is the treatment of choice. Pentamidine is another option for severe disease. Other agents: Clindamycin/Primaquine, Trimethoprim/Dapsone, Atovaquone (for mild disease only).
9. Add corticosteroids in addition to anti-PCP antibiotics if the PaO2 < 70 mmHg or A-a gradient > 35-40. Dose: prednisone 40 mg PO BID x 5 days, 40 mg PO QD x 5 days, then 20 mg PO QD x 11 days. Give first dose 15-30 minutes before 1st dose of TMP/SMX.
10. Start antibiotics for bacterial or fungal pneumonia if clinically indicated.
Miller R. HIV-associated respiratory diseases. Lancet. 1996 Aug 3;348(9023):307-12.
1. Volumes have been written on this disease, which should be strongly considered in patients presenting with cough, fatigue, fever, weight loss and night sweats. The following points are intended to help manage cases of suspected or documented TB in the hospital.
2. Chest x-ray findings in primary TB include small homogenous infiltrates, hilar and paratracheal lymphadenopathy and segmental atelectasis. Reactivation TB can manifest in many ways, but typical findings include apical cavitary disease and pneumonic infiltrates in the apical or posterior segments of the upper lobes.
3. In HIV, the radiographic presentation of TB depends on the CD4 count. A “high” CD4 count (> 400) is associated with upper lung zone disease and cavitation. “Low” CD4 count (i.e. ~200) manifests as diffuse disease (including miliary), mid/lower lung zone disease, hilar and mediastinal adenopathy, cavitation less frequent.
4. Any patient with a good story for TB and/or suggestive chest X-ray should be placed in respiratory isolation. As a general rule, it’s always easier to take patients out of isolation after discussion with a specialist than to put them in isolation after they have spent the night coughing TB onto other patients and the staff.
5. To rule out contagious TB, obtain three morning sputum samples for AFB staining and culture (keep patients NPO after midnight while collecting). If patient does not have a productive cough, sputum must be induced by respiratory therapy. Intubated patients can have three sputums collected 8 hours apart through the ET tube.
6. After three negative sputums have been collected, you may take patients out of respiratory isolation. If suspicion for TB is still high, consider bronchoscopy for diagnostic washings ± transbronchial biopsies. Standard cultures take 6-8 weeks to grow TB.
7. For high-risk patients (prisoners, HIV patients with moderate to high clinical and radiographic evidence, immunocompetent patients with high clinical and radiographic evidence, particularly if they share close living quarters with others), anti-TB treatment should be started on the first day of hospitalization and, depending on the clinical scenario, continued until cultures (not smears) return negative.
8. Treatment for TB typically involves 4-drug therapy with isoniazide, rifampin, pyrazinamide and ethambutol. Doses and length of treatment varies given local drug-resistance patterns and immune status of patient.
9. Directly observed therapy (DOT) is the standard of care for patients who complete their treatment outside the hospital.
10. Incarcerated patients need to be cleared by your local TB clinic and the jail medical team prior to going back to jail if they were admitted for ruling out TB.
11. All newly diagnosed tuberculosis cases need to be reported to your local health department or TB Controller within 1 working day. This includes any patient in whom tuberculosis treatment is started, even if smear and culture results are not yet known.
Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001; 345:189-200.
Initial work-up includes the following:
1. If patient has concomitant shortness of breath or pulmonary symptoms, see Infectious diseases: HIV and shortness of breath.
2. Examine the skin carefully. If skin lesions are present, they can facilatate a prompt diagnosis including cryptococcus, histoplasmosis, mycobacterial disease, bacilliary angiomatosis as well as a simple cellulitis secondary to staph or strep.
3. Don’t forget the occult sites including scalp, ears, sinuses, axillae, groin, peri-rectal area, and interdigital foot spaces.
4. Obtain a chest x-ray.
5. Consider head CT (and if clinically indicated, chest and/or abdominal CT).
6. Blood cultures x 2 with culture for AFB including MAC (this requires a green top tube and can be part of a regular blood draw, as it is not a sterile culture). Stool for C. difficile (if history of antibiotics), fecal WBC, stool culture, and O&P x 3 if patient has diarrhea.
7. Consider lumbar puncture: send CSF for cell count, protein, glucose, and CrAg (all stat). Also send CSF for C&S, VDRL, and viral culture (if high clinical suspicion).
8. Labs should include electrolytes, BUN, creatinine, CBC, differential, platelets, LDH, LFTs, hepatitis serologies (if suspected or unknown), serum CrAg.
9. Consider empiric antibiotic therapy.
1. Classicially defined as three weeks of illness with T > 38.3ºC on several occasions. New definition is persistant T > 38.3ºC and failure to reach diagnosis after one week of inpatient evaluation.
2. Etiology:
3. Work-up: FUO work-up includes repeat blood cultures (preferably when the patient has been off antibiotics for a few days. Make sure cultures are held for 2 weeks), chest X-rays, CT of abdomen and pelvis and chasing any abnormal clinical findings (e.g. LP and head CT for headache, echo for murmur). Blood smears to rule out malignancy, malaria, and relapsing fever are helpful. Bone marrow biopsy tends to be low-yield in FUO except in HIV patients, in whom mycobacterial infiltration of marrow is a more common cause of FUO. Radionuclide studies (e.g. tagged WBC scan) can be frustrating in a patient without localizing syptoms given high rate of false-positive and false- negative results. Gallium is more helpful than indium because you can assess for both cancer and infection.
4. Treatment:
Arnow PM, Flaherty JP. Fever of unknown origin. Lancet. 1997 Aug 23;350(9077):575-80.
Armstrong WS, Katz JT, Kazanjian PH. Human immunodeficiency virus-associated fever of unknown origin: a study of 70 patients in the United States and review. Clin Infect Dis. 1999 Feb;28(2):341-5.
1. Sepsis can kill quickly. Successful management requires early identification and intervention.
2. Definitions:
· Systemic inflammatory response syndrome (SIRS): requires two or more of the following:
- Temperature > 38.0ºC (100.4ºF), or < 36.0ºC (96.8 ºF).
- Heart rate > 90 BPM.
- Respiratory rate > 20/min.
- WBC count > 12,000/ml, < 4,000/ml, or > 10% immature bands.
· Sepsis: SIRS plus a documented infection (positive culture for organism).
· Severe Sepsis: sepsis associated with organ dysfunction, hypoperfusion abnormalities, and/or hypotension. Hypoperfusion abnormalities include, but are not limited to, lactic acidosis, oliguria, and/or altered mental status.
3. Initial therapy should focus on the early use of appropriate broad-spectrum antibiotics and surgical intervention as needed. One should try to obtain blood cultures prior to administration of antibiotics, but treatment should not be delayed.
4. Aggressive volume resuscitation should occur early in order to maintain MAP > 65 mmHg. Remember though that the amount of volume should be individualized to the clinical situation. See also Critical Care: Early goal-directed therapy for sepsis.
5. If the patient remains hypotensive or has signs of hypoperfusion despite adequate fluids, start vasopressors (see Cardiology: Pressors and cardiac drips and Critical care: Initial choice of pressor).
6. Always consider Activated Protein C (APC) if available at your hospital. See Infectious diseases: Activated Protein C for sepsis.
American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992 Jun;20(6):864-74.
1. The evidence: untreated sepsis carries a mortality of 50%. APC reduced this mortality with a relative risk reduction of 19% (NNT=14).
2. When giving APC for sepsis, you must balance the potential benefits with the risk of serious bleeding, defined as any intracranial hemorrhage, any life-threatening bleed, or any bleed that required > 3 units PRBC’s per day for 2 consecutive days. During the PROWESS study, the incidence of serious bleeding was 2.0% in the control group compared to 3.5% in the treatment group.
3. Inclusion criteria: in order to receive APC, patients must have a known or suspected infection, meet 3 of 4 SIRS criteria and have evidence of organ/system dysfunction by meeting at least one of the five following criteria:
4. Exclusion criteria:
- Surgery within 12 hours prior to infusion, potential need for surgery during infusion, or active bleeding post-op; trauma.
- History of severe head trauma, intracranial surgery or stroke within 3 months or any history of intracerebral AV malformation, cerebral aneurysm or mass lesion in CNS
- GI bleed within past six weeks.
· Other therapies known to increase risk of bleeding:
- Heparin to treat an active thrombotic event within 8 hours prior to infusion (DVT prophylaxis okay).
- Low-molecular weight heparin at higher-than prophylaxis doses; warfarin.
- Thrombolytic therapy within 3 days prior to infusion.
- Glycoprotein IIb/IIIa antagonists within 7 days prior to infusion.
5. The following were exclusion criteria during the original study, but most experts believe that APC can and should be used in these situations: HIV infection with last CD4 count < 50/mm3, history of bone marrow, lung, liver, pancreas, or small bowel transplant, chronic renal failure requiring hemodialysis or peritoneal dialysis.
6. Treatment: give drotrecogin alfa (Xigris®) at 24 mcg/kg as an infusion for 96 hours.
Bernard GR, Vincent JL, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis.
N Engl J Med. 2001 Mar 8;344(10):699-709.