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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2664_Библиотеки_им_академика_М_И_Перельмана
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USMLE Step 2 CK
l Internal Medicine
Criteria for Surgery in Infective Endocarditis
Major criteria
• CHF, progressive or unresponsive to “simple” measures
• Recurrent systemic emboli
• Persistent bacteremia despite adequate antibiotic therapy
• Fungal etiology
• Extravalvular infection (atrioventricular block, purulent pericarditis)
• Prosthetic valve dehiscence or obstruction
• Recurrence of infection despite adequate therapy
Minor criteria
• CHF, resolved with medical therapy
• Single systemic embolic event
• Large aortic or mitral vegetations on echocardiography
• Premature mitral valve closure in acute aortic insufficiency
• Prosthetic valve infection due to organisms other than highly penicillin-sensitive
streptococci
• Tricuspid endocarditis due to Gram-negative bacilli
• Persistent fever without other identifiable cause
• New regurgitation in an aortic prosthesis
250
Gold Standard Multimedia Inc., 2007
Figure 7-10. Embolic Features of Acute Endocarditis
Chapter 7
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phil.cdc.gov
Figure 7-11. Petechial Hemorrhage, an Embolic
Phenomenon Due to Septicemia/Endocarditis
Prevention of bacterial endocarditis
The number of cardiac lesions which are an indication for endocarditis prophylaxis has markedly diminished over the years. AS, MS, AR, and MR no longer need prophylaxis, even for
dental procedures. Prophylactics are indicated when there is both a serious underlying cardiac
defect and a procedure causing bacteremia.
• Dental procedures: amoxicillin; for penicillin-allergic patients, use clindamycin,
azithromycin, clarithromycin, or cephalexin
• Urinary or GI procedures: no longer require prophylaxis
l Infectious Diseases
Cardiac Conditions Which Do Require Prophylactic Therapy
• Prosthetic cardiac valves, including bioprosthetic and homograft valves
• Previous bacterial endocarditis, even in the absence of heart disease
• Most congenital cardiac malformations, especially cyanotic lesions (negligible risk
with isolated ASD) if not repaired
Conditions Which Do Not Require Prophylactic Therapy
• Surgically corrected systemic pulmonary shunts and conduits
• Rheumatic and other acquired valvular dysfunction, even after valvular surgery
• Hypertrophic cardiomyopathy
• Mitral valve prolapse with valvular regurgitation
• Surgically repaired intracardiac defects
Dental or Surgical Procedures Which Predispose to Endocarditis
•
Dental procedures known to induce gingival or mucosal bleeding, including profes-
sional cleaning
• Tonsillectomy and/or adenoidectomy
Procedures in Which Indication for Prophylaxis Is Unclear
• Surgical operations that involve intestinal or respiratory mucosa
Anatomic Defects or Conditions Which Require Prophylaxis
• Prosthetic valves
• Unrepaired cyanotic heart disease
• Previous endocarditis
• Transplant status
251
USMLE Step 2 CK
l Internal Medicine
LYME DISEASE
A couple comes to your office after a recent camping trip. The woman has
sustained a tick bite but did not develop any symptoms. The man has developed
a red skin lesion that resolved and was followed by the onset of facial palsy. He
does not recall having sustained a tick bite.
Definition/Etiology. Lyme disease is spread by the bite of the Ixodes scapularis (dammini)
tick. On the basis of animal studies we know that the tick needs at least 24 hours of attachment to transmit the Borrelia burgdorferi organism. The tick is small, and the bite is often not
remembered.
Clinical presentation. Symptoms begin 3−30 days after the bite of the tick. Eighty percent of
patients develop the erythema migrans rash at the site of the bite. (An erythematous patch,
which may enlarge in the first few days, may have partial central clearing, giving it a “bull’seye” appearance, although this is not commonly seen.) Even without treatment, the rash
resolves in several weeks. A flulike illness with fever, chills, and myalgias occurs in half of
patients.
Neurologic symptoms develop several weeks later in 10−20% of patients. This is most com-
monly paralysis of the seventh cranial nerve (facial paralysis) and may be bilateral. Meningitis,
encephalitis, headache, and memory disturbance may develop as well. Cardiac symptoms
develop in <10% of patients and is most commonly AV heart block. Myocarditis, pericarditis,
and various forms of arrhythmias may develop as well. Joint involvement may develop months
to years later in up to 60% of patients, most commonly as a migratory polyarthritis, although a
small percentage can have chronic monoarticular arthritis, most commonly affecting the knee.
Diagnosis. Definite diagnostic criteria for Lyme are the development of the erythema migrans
rash combined with the presence of at least one late manifestation, as well as laboratory
confirmation of the presence of the organism. Most patients are treated on the basis of the
presence of the rash alone. Serologic testing is the most commonly used test. An ELISA test
combined with a western blot is the standard method of establishing the diagnosis. The problem with the serologic test is that it often does not distinguish between current and previous
infection. Also, in early disease when patients have the rash, testing is often negative because
patients have not had sufficient time to mount an immune response. In such circumstances,
treatment should be given based on strong clinical suspicion, and serologic testing should not
be done. Serology will almost always be positive later in the course of the disease.
Treatment. Minor symptoms are treated with doxycycline or amoxicillin. The rash, facial palsy,
and joint pain can be treated with oral doxycycline. More serious manifestations such as heart
block, meningitis, myocarditis, or encephalitis are treated with IV ceftriaxone. In other words,
all cardiac and serious neurologic manifestations should be treated with IV ceftriaxone.
252
Centers for Disease Control and Prevention,
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
James Gathany
Figure 7-12. Erythema-Migrans – Lyme Disease
Chapter 7
l Infectious Diseases
ROCKY MOUNTAIN SPOTTED FEVER
Etiology. R. rickettsii is transmitted by the wood tick. Mid-Atlantic coast, upper South, and
Midwest are the most common areas.
Clinical Findings
• More common in spring and summer
• Triad: abrupt onset of fever, headache, and rash (erythematous maculopapules). This
disease starts at wrist and ankles and spreads centripetally (can involve palms and soles).
• Differential diagnosis with syphilis
Signs and Symptoms. Confusion, lethargy, dizziness, irritability, stiff neck, and GI symptoms.
Rash starts before day 6.
Diagnosis. Specific serology: Biopsy of skin lesion
Treatment. Doxycycline
phil.cdc.gov
Figure 7-13. Rash of Rocky Mountain Spotted Fever on an Infant
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USMLE Step 2 CK
l Internal Medicine
ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)
AIDS is caused by the human immunodeficiency virus (HIV). The primary mechanism of HIV
is infection of a particular subset of T lymphocytes called CD4 cells, often just referred to as
T cells. Over time, HIV decreases the number of CD4 cells. As a person’s CD4 count drops, he
becomes at increasing risk of developing opportunistic infections and certain malignancies.
The mode of HIV acquisition is different in different parts of the world. In the United States,
the earlier part of the epidemic was fueled by men who had sex with men (MSM) and injection
drug use. Nowadays, the most common risk factors are MSM and heterosexual intercourse. In
women, the most common mode is heterosexual transmission. In most developing countries,
including Africa, Asia, and Latin America, heterosexual transmission is the primary mode. There
is often a 10-year lag between contracting HIV infection and developing the first symptoms.
This is because CD4 cells drop at a rate of 50−100/mL/year without therapy. It would take 5−10
years to drop from a normal level of around 700/mm3 to a CD4 count of 200/mm3.
Opportunistic Infections in AIDS
Pneumocystis jirovecii (formerly carinii) (CD4 count <200/µL)
Principal Manifestations. pneumonia; dyspnea on exertion; dry cough; fever; chest pain; usually subacute onset and progression.
Principal Diagnostic Test. Bronchoscopy with bronchoalveolar lavage for direct identification
of the organism. Chest x-ray reveals bilateral, interstitial infiltrates. Pneumothorax may be
present and it is possible to have PCP pneumonia with a normal chest x-ray. Serum LDH is
usually moderately elevated.
Treatment and Side Effects
• Trimethoprim-sulfamethoxazole (TMP-SMZ) is the first-line therapy for mild-severe
disease and may cause a rash. Alternative therapy for mild-moderate disease is a combination of dapsone and trimethoprim or primaquine and clindamycin or atovaquone
or trimetrexate (with leucovorin).
• Pentamidinepancreatitis, hyperglycemia, hypoglycemia
• Steroids are used as adjunctive therapy for any patient with severe pneumonia. Severe
o
is defined with a Pa
Prophylaxis (in Order of Preference)
• TMP/SMZ orally—this is most effective.
• Dapsone
• Atovaquone
• Aerosolized pentamidine—fails the most
• Prophylaxis of PCP may be discontinued if antiretrovirals raise CD4 count >200/mL
for >6 months.
of <70 mm Hg or an A-a gradient of >35 mm Hg.
2
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Cytomegalovirus (CD4 <50/µL)
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Principal Manifestations
• Retinitis: blurry vision, double vision, or any visual disturbance in a patient with a
very low CD4 count
• Colitis: diarrhea (<20% of patients)
• Esophagitis: odynophagia, fever, retrosternal chest pain (endoscopy reveals multiple
shallow ulcers in the distal esophagus)
• Encephalitis: altered mental status, cranial nerve deficits
Principal Diagnostic Tests
• Funduscopy for retinitis
• Colonoscopy with biopsy for diarrhea or upper GI endoscopy with biopsy of ulcers
Treatment and Side Effects
• Valganciclovir—an oral prodrug of ganciclovir, achieves levels in the serum comparable to IV ganciclovir. This drug can be used to treat CMV retinitis (along with intravitreal ganciclovir) and GI manifestations of CMV disease. IV ganciclovir is reserved
for serious CNS infections and for patients that cannot tolerate oral medications.
Foscarnet and cidofovir are used when ganciclovir resistance or failure occurs.
• Ganciclovirneutropenia or foscarnet-renal toxicity
• Cidofovirrenal toxicity
Chapter 7
l Infectious Diseases
Prophylaxis. Valganciclovir is used for maintenance therapy. Primary prophylaxis is not
indicated.
Mycobacterium avium complex (CD4 <50/mL)
Principal Manifestations. A ubiquitous atypical mycobacteria found in the environment; mode
of infection is inhalation or ingestion. Fevers, night sweats, bacteremia, wasting, anemia, diarrhea.
Principal Diagnostic Tests
• Blood culture
• Culture of bone marrow, liver, or other body tissue or fluid
Treatment. Clarithromycin and ethambutol ± rifabutin.
Prophylaxis
•
Azithromycin orally once a week or clarithromycin twice a day
• Prophylaxis may be discontinued if antiretrovirals raise the CD4 count >100/mL for
several months.
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USMLE Step 2 CK
l Internal Medicine
Toxoplasmosis (CD4 <100/µL)
Principal Manifestation. Brain mass lesion: headache, confusion, seizures, and focal neurologic
deficits
Principal Diagnostic Tests
• CT or MRI scan of the head showing a “ring” (contrast) enhancing lesion with edema
and mass effect. A trial of specific therapy is given for 2 weeks, and the scan is repeated. Shrinkage of the lesions is considered diagnostic.
• Brain biopsy is occasionally necessary if there is no shrinkage of the lesions with treatment for toxoplasmosis.
Treatment. Pyrimethamine and sulfadiazine. Clindamycin can be substituted for sulfadiazine
in the sulfa-allergic patient. Leucovorin is given to prevent bone marrow suppression.
Prophylaxis
• TMP/SMZ
• Dapsone
Cryptococcosis (CD4 <100/µL)
Principal Manifestation. Meningitis; patients mostly present with fever, headache, and malaise.
Principal Diagnostic Tests
• Lumbar puncture with initial evaluation by India ink and then specific cryptococcal
antigen testing. A lower CSF cell count implies worse disease.
• Serum cryptococcal antigen testing. A high antigen titer, high opening pressure, and
low CSF cell count all imply a worse prognosis.
Treatment. Amphotericin intravenously for 10−14 days at least (with flucytosine), followed by
fluconazole orally for maintenance and surpressive therapy.
Prophylaxis. Oral fluconazole is not recommended for general use as a prophylaxis. This is
because the incidence of cryptococcal meningitis is too low to demonstrate a mortality benefit with its use.
Vaccinations
All HIV-positive persons should receive vaccinations for pneumococcus, influenza, and hepatitis B.
If the CD4 level is >200, even varicella vaccine can be given.
Monitoring the Immune System
CD4 count monitoring and viral load testing can be compared to the staging of cancer in
terms of assessing prognosis for the patient. They are indispensable for determining appropriate treatment.
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Chapter 7
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CD4 cell count
The CD4 count is the most accurate method for determining what infections or other diseases the patient is at risk for. At the present time the CD4 count provides an assessment of
the extent of immunologic damage at the time of diagnosis and is usually the most important
factor when deciding the timing of therapy. It is also the strongest predictor of disease progression and survival. Without treatment, CD4 count drops 50−100 cells per year.
The following is an approximate breakdown of when the risk of certain diseases begins to increase.
CD4 Count
700−1,500/mL: Normal
200–500/mL: Oral thrush, Kaposi sarcoma, tuberculosis, Zoster
100–200/mL: Pneumocystis carinii pneumonia, disseminated histoplasmosis and
coccidiomycosis
<100/mL: Toxoplasmosis, Cryptococcus, cryptosporidiosis, disseminated herpes
simplex
<50/mL:
Cytomegalovirus, Mycobacterium avium complex. Progressive,
multifocal leukoencephalopathy (PML), CNS lymphoma
l Infectious Diseases
In addition to determining the risk of opportunistic infections, the other uses of the CD4
count are to determine:
• When to start prophylactic medications
• When to initiate antiretroviral medications (<500)
• Adequacy of response to antiretroviral medications (though the best test to monitor
response to therapy is the HIV-RNA viral load)
Viral load monitoring
Tests now exist to give a numerical value to the quantity of HIV in the blood. Viral load can
be compared to glucose level for patients with diabetes. Monitoring of viral load is the best
method to monitor adequate response to therapy when the patient is on antiretroviral medications and the goal is undetectable viremia. High viral loads indicate a greater risk of complications of the disease and a worse prognosis. A high viral load generally indicates that the
level of CD4 cells is going to drop more rapidly.
Other uses of viral load testing are to determine:
• When to initiate antiretroviral medications
• The adequacy of response to antiretroviral medications; usually with current assays,
the goal is complete suppression of viremia with <50 to 70 copies of HIV-RNA/mL
Viral sensitivity/resistance monitoring
Viral sensitivity testing is done to determine which antiviral medications will be effective in an
individual patient. Sensitivity testing should always be done if a patient is failing a combination
of medications and a change in therapy is necessary. It should also be done in any pregnant
woman who has not been fully suppressed on the initial combination of medications.
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l Internal Medicine
Antiretroviral Therapy
Currently available agents and their major adverse effects
Nucleoside Reverse Transcriptase Inhibitors
• Zidovudine (ZDV or AZT)Leukopenia, anemia, GI
• Didanosine (DDI)Pancreatitis, peripheral neuropathy
• Stavudine (D4T)Peripheral neuropathy
• Lamivudine (3TC)Nothing additional to placebo
• Emtricitabine—Structurally related to lamivudine; few side effects as for lamivudine
• Tenofovir is a nucleotide analog as compared to the others that are nucleoside analogs.
• Abacavir—Most important side effect is a hypersensitivity reaction that usually occurs
in the first 6 weeks of therapy. Patients may have a rash, fever, nausea/vomiting, muscle and joint aches, and shortness of breath. In these cases, the drug should be immediately stopped and never restarted because recurrence of hyperactivity symptoms can
• Zalcitabine (DDC)Pancreatitis, peripheral neuropathy, lactic acidosis
Protease Inhibitors. Hyperlipidemia, hyperglycemia, and elevated liver enzymes for all in the
group; abnormal fat loss (lipoatrophy) from the face and extremities with redistribution of fat
in the back of the neck and abdominal viscera can be seen.
• NelfinavirGastrointestinal
• IndinavirNephrolithiasis (4%), hyperbilirubinemia (10%)
• RitonavirSevere GI disturbance
• SaquinavirGastrointestinal
• Amprenavir
• Lopinavir/Ritonavir combination—Diarrhea
• Atazanavir—Diarrhea, asymptomatic hyperbilirubinemia
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Non-Nucleoside Reverse Transcriptase Inhibitors. These drugs are noncompetitive inhibitors of reverse transcriptase.
• EfavirenzNeurologic; somnolence, confusion
• NevirapineRash, hepatotoxicity
• Delavirdine—Rash
• Rilpivirine
Guidelines for starting therapy
Start therapy once HIV is diagnosed, regardless of CD4 count. Regarding what to start:
• Use 2 nucleosides combined with a protease inhibitor or
• Use 2 nucleosides combined with efavirenz
• Emtricitabine, tenofovir, and efavirenz are available as a single pill once a day.
Chapter 7
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A combination therapy (highly active antiretroviral therapy, HAART) should be used with
medications having synergistic activity by acting at different sites of the virus replicative
process; hence current guidelines recommend two NRTIs (usually tenofovir/emtricitabine or
zidovudine/lamivudine) combined with either a NNRTI (efavirenz preferred) or a PI (atazanavir/ritonavir, fosamprenavir/ritonavir, or lopinavir/ritonavir).
Giving “boosted protease inhibitors” is the practice of giving most protease inhibitors in
combination with a low dose of ritonavir (also a PI). Ritonavir given alone as a PI has modest efficacy and significant drug interactions, but when given in a low dose with other PIs, it
decreases their metabolism and enables higher drugs levels of the “boosted” PI over a prolonged period of time. This increases chances of success and also decreases pill burden.
Any regimen that increases the CD4 count and drops the viral load to undetectable amounts
or close to undetectable amounts is considered adequate therapy. When starting medication,
a drop of at least 50% of viral load in the first month is expected to indicate adequate therapy.
l Infectious Diseases
Pregnant Patients
Without treatment, approximately 25−30% of children born to HIV-positive mothers will
truly be HIV positive. All children at birth will carry the maternal antibody to the virus and
will be positive by ELISA testing, but only 25−30% will remain truly infected.
• Pregnant women with serious disease (i.e., low CD4 or high viral load) should be treated
fully for their HIV infection. That is, they should get triple antiretroviral therapy as you
would in a nonpregnant person.
• C-section is only used routinely in those whose CD4 count and viral load are not controlled with medications (when viral load is >1000 copies/mL of HIV-RNA at the time
of delivery).
• Treatment is indicated in all pregnant women. Zidovudine (AZT) should be used in combination with 2 other antiretroviral medications. Even when the CD4 is high and viral
load is <1000, you should start therapy as soon as you know the patient is pregnant.
• The only known teratogen is efavirenz in animal studies.
Breast Feeding
Breast feeding is associated with transmission of virus to the infant. If a pregnant woman is
already on antiretrovirals, she should continue on them. She should start immediately regardless of gestational age. If the woman has high CD4 cells and does not need treatment for herself,
combination therapy can end after delivery. The majority of women can deliver with a normal
vaginal delivery. Avoid efavirenz in pregnancy.
Note
Efavirenz is the only
antiretroviral medication
that is contraindicated
in pregnancy.
Postexposure Prophylaxis (e.g., Needlestick Injury)
All persons with serious exposure to blood containing body fluids of HIV-positive patients
should receive AZT, lamivudine, and nelfinavir or raltegravir or any other fully suppressive
3-drug combination for 4 weeks. Modify the regimen as needed to ensure compliance. The
point is to use any fully suppressive combination for at least 4 weeks; we know zidovudine
alone will decrease the risk of transmission by 80%. We don’t know how much the combination will decrease transmission.
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