Perelman School of Medicine at the University of Pennsylvania

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Infectious Diseases Pearls

C.difficile Infection

Which antibiotics are most associated with causing C.diff infections?

  • Most frequently associated: fluoroquinolones, clindamycin, cephalosporins
  • Less associated: macrolides, trimethoprim-sulfamethoxazole, penicillins
  • Meta-analysis of antibiotics associated with C.diff:

What is the recurrence rate of C.diff?

How do we grade C.diff severity?

  • Qualifies as severe C.diff infection if:
    • WBC > 15
    • Cr > 1.5x original
    • Albumin < 3
    • Hemodynamically unstable or ICU admission

How do you treat C.diff?

  • Initial or nonsevere: metronidazole PO
  • Severe: vancomycin PO
  • Can consider: metronidazole IV, vancomycin enema
  • Less commonly: fidaxomicin, rifaximin, fecal transplant
  • Surgery if: toxic megacolon perforation, multiorgan failure
  • 2010 C.diff treatment guidelines by the Society for Healthcare Epidemiology of America (SHEA) and Infectious Diseases Society of America (IDSA):




What are the classifications of infective endocarditis?

  • Native valve versus prosthetic valve
  • Short incubation (acute) versus long incubation (subacute)
  • Culture negative versus culture positive
  • Right sided versus left sided

What are the Duke Criteria for infective endocarditis?

  • Pathologic Criteria:
    • Positive culture of vegetation
    • Vegetation or abscess confirmed
  • Major Clinical Criteria:
    • Positive blood cultures commonly associated with endocarditis
    • Echocardiogram evidence of endocarditis
  • Minor Clinical Criteria:
    • Predisposing heart condition or IV drug use
    • Fever
    • Vascular phenomena (emboli, infarcts, Janeway lesions)
    • Immunologic phenomena (Osler’s nodes, Roth’s spots, glomerulonephritis)
    • Positive blood culture but not meeting major criteria.
  • Requirements for diagnosis: 2 major, 1 major and 3 minor, or 5 minor
  • The original 1994 paper introducing the Duke criteria for endocarditis:

How sensitive is echocardiogram for detecting vegetations?

What are the HACEK organisms in endocarditis?

  • Haemophilus aphrophilus
  • Actinobacillus actinomycetemcomitans
  • Cardiobacterium hominis
  • Eikenella corrodens
  • Kingella kingae
  • Prospective cohort study on the causative organisms of infective endocarditis:

What are the complications of septic emboli?

  • Cardiac: coronary artery embolism (myocardial infarction)
  • CNS: embolic stroke, retinal artery embolism, subdural hemorrhage (mycotic aneurysms)
  • Pulmonary: pulmonary embolism for right sided endocarditis, pleural effusion/empyema
  • Renal: renal emboli
  • Spleen: splenic infarction
  • A 2008 paper found 30% of patients with left-sided infective endocarditis had clinically silent strokes on MRI:




What are the classifications and definitions of sepsis?

  • SIRS: at least 2 of the following: HR> 90, WBC <4 or >12, RR > 20, T <96.8 or > 100.4
  • Sepsis: SIRS + presumed infectious source
  • Severe sepsis: sepsis + end-organ damage (hypotension <90/60), lactate, AKI, ARDS, etc)
  • Septic shock: severe sepsis + hypotension despite fluids
  • Septic shock with multiple organ dysfunction syndrome (MODS): septic shock + 2 or more failing organs
  • 2012 Surviving Sepsis Campaign guidelines:

What are the components of early goal directed therapy in sepsis?

How do we define neutropenic fever?

  • Absolute neutrophil count (WBC x % neutrophils and bands) less than 500 or
  • Absolute neutrophils count less than 1000 but predicted to drop to less than 500 in 48 hours
  • Temperature threshold: 100.4 deg Fahrenheit for at least an hour or a single temperature of 101.0 deg Fahrenheit
  • 2010 Infectious Diseases Society of America (IDSA) guidelines for neutropenic fever:

How would you empirically cover for neutropenic fever?

  • Cefepime (to cover gram negatives including Pseudomonas)
  • Can also consider vancomycin (to cover MRSA mainly if has likely gram positive source)
  • Can also consider either caspofungin or voriconazole for risk of fungal infection
  • If penicillin allergic can consider levofloxacin + aminoglycoside + vancomycin
  • 2010 Infectious Diseases Society of America (IDSA) guidelines for neutropenic fever:

What are the most common sources of fever?

  • Respiratory: influenza, pneumonia
  • Urinary: UTI, pyelonephritis
  • Neuro: meningitis, encephalitis
  • Blood: bacteremia
  • GI: gastroenteritis

What are the most common cryptic sources of fever?

  • Infection: tuberculosis, abdominal abscess, osteomyelitis, CMV/EBV, dental abscess, sinusitis, septic arthritis, sacral decubitus ulcer
  • Coagulopathy: DVT, pulmonary embolism
  • Malignancy: lymphoma, leukemia
  • Connective tissue disorder: temporal arteritis, adult Still’s disease, polyarteritis nodosa, Takayasu, Wegener’s, cryoglobulinemia
  • Other: familial Mediterranean fever



HIV/Opportunistic Infections

How does abacavir hypersensitivity present and how do we test for it?

  • Abacavir is an NRTI (nucleoside reverse transcriptase inhibitor)
  • Severe and sometimes fatal hypersensitivity reactions have occurred
  • Hypersensitivity to abacavir can present with fever, rash, GI distress, fatigue, dyspnea, cough.
  • Remember that abacavir can be present in antiretroviral combination drugs.
  • Test patients for the HLA-B*5701 allele which if detected places a patient at higher risk for a hypersensitivity reaction to abacavir.
  • Analysis of the sensitivity of abacavir genetic testing in predicting predisposition to hypersensitivity reactions:

What are the time period and symptoms of an acute HIV infection?

  • Acute HIV infection refers to the time between exposure to the HIV virus and the completion of the initial immune responses which generally lasts around 2-3 months.
  • Blood HIV antibody tests may still be negative while the viral load will usually be detectable.
  • Symptoms of acute HIV infection can include fevers, night sweats, weight loss, malaise, lymphadenopathy, sore throat, GI upset, myalgias.
  • JAMA Rational Clinical Examination on Does this Adult Patient have Early HIV Infection?

What are the classes of HIV antiretroviral agents?

  • Nucleoside reverse transcriptase inhibitors (NRTIs)
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
  • Protease inhibitors (PIs)
  • Integrase inhibitors (INSTIs)
  • Fusion inhibitors (FIs)
  • Chemokine receptor antagonists (CCR5 antagonists)

What are the CNS complications of HIV?

  • CNS complications caused by HIV itself:
    • HIV-associated neurocognitive disorder (HAND syndrome) which includes HIV encephalopathy or AIDS dementia complex
    • Some peripheral neuropathies
    • Vacuolar myelopathy
  • CNS complications secondary to immunodeficiency:
    • CNS lymphoma
    • Progressive multifocal leukoencephalopathy (PML)
    • Kaposi sarcoma
    • Infectious processes: tuberculous meningitis, cryptococcal meningitis, toxoplasmosis, CMV encephalitis, neurocysticercosis

In what CD4 count range do we consider Cryptococcus?

  • Cryptococcal disease usually occurs with CD4 count below 100.
  • For CNS cryptococcosis, usually see meningitis signs with fever, headache, nausea, stiff neck, altered mental status, photophobia, and visual changes.

How do we test for Cryptococcus?

  • Test for Cryptococcal antigen in the serum and CSF and perform a CSF and blood culture with India ink stain.
  • In a lumbar puncture, opening pressure on lumbar puncture may be greater than 200mm H2O. Glucose is generally normal and protein is usually high.
  • Sensitivity and specificity of Cryptococcus CSF antigen tests:

What are the initial treatments for Cryptococcal meningitis?

  • Initial therapy usually consists of amphotericin B and flucytosine followed by fluconazole.
  • May need serial lumbar punctures or a CSF shunt to relieve headache.

What is the definition of AIDS?

  • AIDS results from a chronic HIV infection
  • Requires HIV infection with CD4 count less than 200 or an HIV-associated opportunistic infection or disease.

Should all HIV patients be on antiretroviral therapy?

What are the components of initial antiretroviral therapy?

  • Most HIV regimens include 2 NRTIs (nucleoside reverse transcriptase inhibitors) in combination with an NNRTI (non-nucleoside reverse transcriptase inhibitors), protease inhibitor, or integrase inhibitor.
  • Remember to check an HLA-B*5701 allele test if abacavir is a possible therapy given the predisposition to hypersensitivity in patients with the allele.

What parts of the body are most involved in Kaposi Sarcoma (KS)?     

  • Caused by Kaposi’s sarcoma-associated herpesvirus aka HHV-8
  • Can occur with or without HIV
  • When associated with AIDS often presents as red or purple macules to progress to papules, nodules and plaques often on the head, neck, trunk, back, and mucus membranes
  • Can spread to stomach, intestines, lungs, and lymph nodes
  • Treat the underlying cause of immunosuppression.

What are the features of HIV-associated nephropathy (formerly AIDS-associated nephropathy)?

  • Proteinuria (nephrotic range)
  • Azotemia
  • Normal blood pressure
  • Normal to large kidneys on renal ultrasound
  • Renal biopsy showing FSGS (focal segmental glomerulosclerosis)
  • Prevalence of different renal biopsy results in HIV patients:

When do we use post-exposure HIV prophylaxis (PEP) in occupational exposures?

  • Post-exposure prophylaxis is recommended if the source of the exposure has documented HIV.  Post-exposure prophylaxis is optional if the source’s HIV status is unknown.
  • Low-risk exposure (mucous membrane): choose two drug (basic) regimen
  • High-risk exposure (needle stick): choose three drug (expanded) regimen
  • Health care workers are automatically given the three drug regimen
  • Start therapy within hours and continue for 28 days
  • US Public Health Service guidelines recommendations for PEP in occupational exposures:

When do we use post-exposure HIV prophylaxis (PEP) in non-occupational exposures?

  • Non-occupational exposures include injection equipment sharing and sexual contact
  • Risk is based on contact between vagina, rectum, mouth, eye, non-intact skin or percutaneous exposure to any of the following.
  • Substantial risk HIV exposure: blood, semen, vaginal secretions, rectal secretions, breast milk, other bodily fluid contaminated with blood.
  • Negligible risk criteria: urine, saliva, sweat, nasal secretions that are not contaminated with blood .
  • If substantial risk and present within 72 hours, offer a post-exposure prophylaxis with 3 agents.
  • If patient presents more than 72 hours after exposure or meets negligible risk criteria post-exposure prophylaxis is not recommended.
  • For questions about post-exposure prophylaxis, clinicians can call the National Clinician’s Post-Exposure Prophylaxis Hotline (888-448-4911).

Who is at risk for progressive multifocal leukoencephalopathy (PML)?

  • PML is a demyelinating CNS disease due to the JC virus that infects oligodendrocytes
  • It can happen in other diseases that cause immunosuppression or being on immunosuppressants.
  • Occurs almost exclusively when CD4 count is < 200.
  • Suspect PML in patients with slow onset of focal neurologic symptoms with imaging that shows multifocal lesions.
  • May be able to detect the JC virus in the CSF via PCR (74-93% sensitivity).
  • Treatment is generally based on treating HIV with HAART.

What is the risk of HIV transmission in health care workers?

  • The following are risks of transmission of HIV from an HIV-positive source
    • Percutaneous (needles, bloody devices): 1 in 300 (0.3%)
    • Cutaneous (non-intact skin): 1 in 1000 (0.09%
    • Mucus membrane (large volume): 1 in 1000 (0.09%)
    • The original 1997 NEJM paper showing the incidence of HIV transmission in health care workers:

Who is at risk of toxoplasmosis?

  • Toxoplasmosis is caused by the intracellular parasite Toxoplasma gondii.
  • Toxoplasmosis usually affects HIV patients with CD4 < 200 and especially when < 50.
  • Exposure is often related to undercooked meat, soil, or cats.

What signs/symptoms and test results are suspicious for toxoplasmosis?

  • Patients can present with mental status or personality changes, seizures, hemiparesis, aphasia, ataxia, cranial nerve palsies, vision changes.
  • Generally diagnose with CSF PCR for Toxoplasma gondii DNA, clinical symptoms, and radiologic changes. May be helpful to have IgM and IgG of anti-Toxoplasma gondii antibodies.

What is the initial treatment for toxoplasmosis?

  • Typical treatment includes pyrimethamine, sulfadiazine, and folinic acid.



What are the most common causes of bacterial meningitis?

  • Streptococcus pneumoniae
  • Neisseria meningitidis
  • Listeria monocytogenes
  • Streptococcus agalactiae
  • Haemophilus influenzae
  • Escherichia coli

What is the recommended initial therapy for bacterial meningitis?

  • Age < 50 years: ceftriaxone/vancomycin
  • Age > 50 years: ceftriaxone/vancomycin/ampicillin
  • Immunocompromised: cefepime/vancomycin/ampicillin
  • Head trauma/neurosurgery related: cefepime/vancomycin
  • 2004 IDSA guidelines for bacterial meningitis management:

Which fungi are known for causing meningitis?

  • Crytopococcus
  • Coccidioides immitis
  • Histoplasma capsulatum
  • Candida species
  • Sporothrix schenckii
  • Investigation of CSF flow cytometry for assessing fungal burden in cryptococcal meningitis:

In what CD4 count range do we consider Cryptococcus?

  • Cryptococcal disease usually occurs with CD4 count below 100.
  • For CNS cryptococcosis, usually see meningitis signs with fever, headache, nausea, stiff neck, altered mental status, photophobia, and visual changes.

How do we test for Cryptococcus?

  • Test for Cryptococcal antigen in the serum and CSF and perform a CSF and blood culture with India ink stain.
  • In a lumbar puncture, opening pressure on lumbar puncture may be greater than 200mm H2O. Glucose is generally normal and protein is usually high.
  • Sensitivity and specificity of Cryptococcus CSF antigen tests:

What are the initial treatments for Cryptococcal meningitis?

  • Initial therapy usually consists of amphotericin B and flucytosine followed by fluconazole.
  • May need serial lumbar punctures or a CSF shunt to relieve headache.

What are the CSF characteristics of bacterial and viral meningitis?

  • Bacterial meningitis: opening pressure high, WBC very high with neutrophils, glucose low, protein high
  • Viral meningitis: opening pressure normal, WBC high with lymphocytes, glucose normal, protein normal or slightly elevated
  • JAMA Rational Clinical Examination series on interpreting lumbar puncture results for diagnosing bacterial meningitis:

What are the signs and symptoms of bacterial meningitis?

  • Most common triad: fever, headache, neck stiffness
  • Other potential symptoms: nausea/vomiting, photophobia, confusion/irritability
  • Analysis of the diagnostic accuracy of Kernig’s and Brdzinski’s signs in meningitis:

What are the most common causes of viral meningitis and their treatments?

  • Herpes simplex (HSV): acyclovir (though some advocate only treating Herpes simplex meningitis if encephalitis is also present)
  • Cytomegalovirus (CMV): ganciclovir or foscarnet




What is the difference between acute and chronic osteomyelitis?

  • Acute: infiltration of neutrophils, congested/thrombosed vessels
  • Chronic: has necrotic bone with granulation/fibrous tissue, mixed inflammatory cells

For osteomyelitis should you treat or biopsy first?

  • Since blood cultures are only positive in 50% of osteomyelitis cases, bone biopsy is the best way to guide antibiotic treatment
  • Bone biopsies should be done either before all antibiotics or at least 48 hours after discontinuation of antibiotics
  • If osteomyelitis is suspected but the patient is clinically stable it is best to get the bone biopsy first then start antibiotics
  • Comparison of bone biopsies versus foot ulcer swabs in diagnosing osteomyelitis:

What are the most common causes of bacterial osteomyelitis?

  • Adults: Staph aureus, less commonly Enterobacter and Streptococcus
  • Sickle cell patients: Staph aureus, but characteristically Salmonella

What is the pathophysiology of osteomyelitis?

  • Bacteria enter bone causing an inflammatory reaction and cell death or necrosis within 48 hours
  • Bacteria and inflammation spread through the shaft of the bone into the Haversian systems and then periosteum
  • Subperiosteal abscess forms causing further bone necrosis
  • Periosteum ruptures and leads to an abscess in the surrounding soft tissue and formation of a draining sinus tract

How do you monitor treatment response for osteomyelitis?

  • Can trend C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) with treatment
  • Repeat imaging is reserved for those without improvement on antibiotics

Which antibiotics have good bone penetration for osteomyelitis treatment?

  • Levofloxacin
  • Trimethoprim-sulfamethoxazole
  • Metronidazole
  • Linezolid
  • Clindamycin




What are the types of pneumonia?

  • Viral pneumonia
  • Bacterial pneumonia
    • Community-acquired pneumonia
    • Hospital-acquired pneumonia
    • Healthcare-associated pneumonia
    • Ventilator-associated pneumonia
    • Aspiration pneumonia
  • Fungal pneumonia
  • Idiopathic interstitial pneumonia (non-infectious)
  • JAMA Rational Clinical Examination on Does this Patient have Ventilator-Associated Pneumonia?

What physical exam findings suggest pneumonia?

What are physical exam findings that you can use to distinguish pneumonia from pleural effusion?

  • Tactile fremitus will be increased in consolidation and decreased with effusion
  • Consolidation should also produce egophony (E to A change)

What does CURB-65 stand for and how does it affect pneumonia treatment?

  • CURB-65 score used to determine if a patient should be hospitalized
  • C=confusion, U=Urea > 20, R=Respiratory rate>30, B=BP <90/60, 65=Age >=65 (1 pt each)
  • Score 0-1 = likely can be managed at home
  • Score 2 = close followup or short hospitalization
  • Score 3-5 = hospitalization recommended
  • Original 2003 Thorax paper introducing the CURB-65 score:

What organisms generally cause community acquired pneumonia?

  • Strep pneumoniae (most common), Staph aureus, Haemophilus influenzae, Legionella, Pseudomonas, viruses

What are the criteria for healthcare-associated pneumonia?

  • Recent hospitalization in the last 90 days for at least 48 hours
  • Resident in a nursing home or long-term care facility
  • All dialysis patients
  • Anyone who has received IV antibiotics or chemotherapy in the last 30 days

What are the criteria for hospital-acquired pneumonia?

  • Pneumonia that occurs 48 hours or more after admission and was unlikely to be present on admission

How do we empirically cover for bacterial pneumonia?

  • Community-acquired pneumonia: ceftriaxone/azithromycin or levofloxacin alone
  • Healthcare-associated pneumonia/ventilator-associated pneumonia: cefepime/vancomycin

How do you switch from IV antibiotics to PO antibiotics in CAP treatment?

  • Switch to IV can happen early
  • No need to observe patients in the hospital after switching

What is the duration of antibiotics for pneumonia treatment?

What is the role of the MRSA swab in treatment of patients hospitalized for pneumonia?

  • MRSA swab has excellent negative predictive value (99%) for MRSA pneumonia in populations with low MRSA pneumonia incidence

What is the role of follow-up chest X-ray after resolution of pneumonia?

  • Not routinely indicated, but can be considered in patients over the age of 50, especially male smokers, to rule out underlying lung cancer
  • Should be obtained 7-12 weeks after treatment

What are the concerns about daptomycin in pneumonia?

  • If you are trying to cover MRSA pneumonia and either cannot use vancomycin or the pathogen is resistant to vancomycin, you cannot use daptomycin
  • Daptomycin is inactivated by the surfactant in the lungs



What are the most common chest X-ray findings in different forms of tuberculosis?

  • Primary TB: infiltrate in middle or lower lung regions
  • Reactivation TB: lesions in upper lobes or apices of lower lobes
  • Healed and latent TB: pulmonary nodules in the hilar area or upper lobes or also tuberculomas (calcified nodules)
  • Cavity: indicates advanced infection with high pathogen load
  • Miliary TB: small nodules resembling seeds
  • Pleural TB: pleural effusion suggestive of empyema

What are the most common manifestations of extrapulmonary tuberculosis?

  • Tuberculous meningitis              
  • Skeletal TB (if it involves the spine then is called Pott disease)
  • Genitourinary TB (may present as a scrotal mass, prostatitis, orchitis, epididymitis or similar to pelvic inflammatory disease)
  • Gastrointestinal TB: nonhealing mucosal ulcers, dysphagia, abdominal pain similar to peptic ulcer disease, malabsorption in the small intestine, or hematochezia/diarrhea in the large intestine

What are the components of RIPE therapy and their side effects?

  • Rifampin: liver dysfunction, red secretions (tears, urine), rash, fever, GI distress
  • Isoniazid: liver dysfunction, peripheral neuropathy, B6 deficiency
  • Pyrazinamide: liver dysfunction, joint pain
  • Ethambutol: liver dysfunction, red-green color blindness and optic neuritis

What are the risk factors for tuberculosis transmission?

  • These four risk factors help determine how easily TB is transmitted
    • Immune status of the exposed person
    • Number of organisms expelled
    • Concentration of organisms
    • Length of time exposed to contaminated air



Urinary Tract Infection

Who requires asymptomatic bacteriuria treatment?

  • Only treat asymptomatic bacteriuria for the following groups:
    • Pregnancy
    • About to or recently had urologic procedure
    • Renal transplant
  • Meta-analysis of nine trials showing no reduction of symptomatic UTIs by treating asymptomatic bacteriuria:

What is the differential diagnosis of dysuria?

  • Urinary tract infection
  • Nephrolithiasis
  • Vaginitis (Candida, bacterial vaginosis, trichomonas)
  • Pelvic inflammatory disease
  • Urethritis (gonorrhea, Chlamydia)
  • Structural urethral abnormality (urethral diverticula, stricture)

What are the empiric treatment choices for an uncomplicated UTI?

What are the empiric treatment choices for pyelonephritis?

What are the criteria to be called a complicated UTI?

  • Complicated UTI criteria (one of the following):
    • Hospital acquired infection
    • Symptoms for 7 days before seeking care
    • Renal failure, urinary tract obstruction
    • Indwelling urinary catheter or stent or nephrostomy tube
    • Functional abnormality of urinary tract
    • Renal transplant
    • Immunosuppression
    • Pregnancy, diabetes

What are the empiric treatment choices for a complicated UTI?

  • Oral therapy: levofloxacin
  • IV therapy: cefepime (less preferably levofloxacin)