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4/20/2015
Board review Part II
Paras Patel MD. Q 1
A previously healthy 24‐year‐old man is evaluated in the emergency department because he has had generalized headaches for the past four weeks. His headaches have progressively worsened, and during the past two days, he also has noted blurry vision. The patient is awake and alert. Temperature is 38.2 C (100.7 F), pulse rate is 66 per minute, and blood pressure is 145/90 mm Hg. No icterus is present. The conjunctivae are pale, and the fundi have papilledema. The neck is supple, and no lymph node enlargement is noted. Cardiopulmonary examination reveals that the heart has a grade 2/6 systolic murmur, and the chest is clear to auscultation. The liver and spleen are not enlarged. No rash is present. Leukocyte count 2600/mcL ,90% neutrophils, 6%, lymphocytes, 4% monocytes. Rapid HIV test is positive. Cell count is 9 /mcL ; 100% lymphocytes, Glucose 26 mg/dL
Total proteins 156 mg/dL , Cryptococcal antigen 1:512 Gram stain reveals budding yeast. Treatment is initiated with liposomal amphotericin B and 5‐flucytosine. Which of the following should also be part of the management of this patient's illness? A.
B.
C.
D.
Initiating prednisone when Cryptococcal therapy is started
Initiating antiretroviral therapy as soon as possible after starting Cryptococcal therapy
Delaying the start of antiretroviral therapy until the Cryptococcal infection is controlled
Minimizing additional lumbar punctures
Ans C
• The timing of antiretroviral therapy (ART) in the treatment of patients who have cryptococcal meningitis has been debated. HIV‐infected patients who have cryptococcal meningitis are profoundly immunosuppressed. • Early ART might decrease the time of continued immunosuppression and thereby decrease the likelihood of the patient's acquiring another opportunistic infection. • On the other hand, this strategy would increase the risk for immune reconstitution inflammatory syndrome (IRIS). • Although IRIS might be tolerated if the problem were in the lung, a lymph node, or the gastrointestinal tract, the closed space of the cranium might make IRIS poorly tolerated. Studies have shown that the strategy of early ART is indeed problematic. • Early ART does not result in increased clearing of Cryptococcus; moreover, it has been associated with increased mortality. • Delaying ART until the cryptococcal infection is under control is the preferred approach. Lumbar punctures to control CSF pressure are a critical part of the management of cryptococcal meningitis. There is no known benefit to the addition of prednisone in the treatment of cryptococcal meningitis. 1
4/20/2015
Cryptococcal Meningitis
• The least‐severe Cryptococcal syndrome is characterized by lung involvement without dissemination. Disseminated disease may include bacteremia and meningitis and occurs in patients with HIV infection and organ transplant recipients.
• Cryptococcal meningitis is the most common form of meningitis in patients with AIDS, who typically present with symptoms such as headache, irritability, and nausea. Most patients have a CD4 cell count of less than 100/microliter. • The diagnosis is based on detection of Cryptococcal antigen in the CSF or culture of C. neoformans in the CSF. The opening CSF pressure is typically elevated.
• Choose fluconazole for primary cutaneous infection without dissemination or for isolated mild pulmonary disease. • For extrapulmonary disease, select amphotericin B plus flucytosine. • Management of elevated intracranial pressure via serial therapeutic lumbar punctures is an essential part of treatment of CNS cryptococcosis.
2
• A 36‐year‐old HIV‐infected man who also has renal failure has been receiving hemodialysis for 18 months. He has been on a stable antiretroviral regimen for three years. For more than a year, he has maintained a CD4 lymphocyte count of greater than 200/mcL [530‐1570]; his current level is 290/mcL, and his viral load has been undetectable. He tells you that his sister has agreed to be a kidney donor for him. He asks about his prognosis after kidney transplantation.
• Which of the following best describes the outcome of kidney transplantation for this HIV‐infected patient compared with that of a non‐
HIV‐infected individual?
(A) Rejection rates are higher, but graft survival is similar
(B) Rejection rates are higher, and graft survival is worse
(C) Rejection rates and graft survival are similar
(D) Rejection rates are similar, but graft survival is worse
Ans C • Kidney transplantation has become an acceptable treatment for selected patients who have well‐controlled
• HIV infection and end‐stage renal disease. However, solid data on outcomes of such transplantations are just emerging. • Results of a recent prospective study of 150 HIV‐infected renal transplant recipients were published and showed that HIV‐infected patients had one‐year and three‐year patient and graft survival rates similar to those of patients without HIV infection in the national transplant registry. • To be included in this study, patients were required to have a CD4 lymphocyte count greater than 200/mcL
and an undetectable HIV viral load for at least 16 weeks before transplantation. • There were certain exclusions for previous opportunistic infections and neoplasms, including progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, central nervous system lymphoma, and visceral Kaposi sarcoma.4
• An interesting finding in the study was that HIV‐infected transplant recipients had high rejection rates compared with those of registry patients (i.e. a 31% rejection incidence at one year versus 12% in controls). Rejection episodes were statistically correlated with later graft loss. • The reason for the high rejection rates after transplantation in HIV‐infected patients is not known with certainty but has been variably posited to be due to difficulty in adjusting antirejection drugs in patients on antiretroviral therapy or to general dysregulation of the immune system caused by HIV. • Most infections seen in the HIV‐infected patients were the usual urinary tract, respiratory tract, and bloodstream infections seen in the general transplant population rather than opportunistic infections. • HIV infection continued to be well controlled after transplantation, with only low‐grade and temporary appearance of detectable virus. One can counsel patients who have HIV infection and renal failure that their three‐year graft and patient survival rates after transplantation should be good. The high rejection rate seen in these patients, however, raises concern that longer term graft survival may not be as good as in patients without HIV infection.
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3. Two weeks ago, a 21‐year‐old student returning to college was ill for four days, with fever, headaches, and fatigue but no other localizing symptoms. Her symptoms resolved, and for ten days she felt well. However, her initial symptoms recurred with the addition of confusion. She was brought to the emergency department and admitted to the hospital. She has spent the past three summers in Europe, hiking and camping in Italy, France, Austria, and Southern Germany. On admission, the patient was awake and alert but oriented only to person. Temperature was 39.0 C (102.8 F), pulse rate was 110 per minute, respirations were 18 per minute, and blood pressure was 105/70 mm Hg. The fundi were normal, conjunctivae were pink, and sclerae were white. No mucous membrane lesions, lymph node enlargement, heart murmur, enlargement of liver or spleen, rash, or focal neurologic findings were detected. Hemoglobin 13.0 g/dL [12‐16], Leukocyte count 4500/mcL [4000‐11,000], Platelet count 256,000/mcL
[150,000‐300,000], Serum creatinine 0.9 mg/dL [0.7‐1.5] Lumbar puncture: Cell count 56/mcL [0‐5]; 80% [30‐45] lymphocytes, Glucose 84 mg/dL [50‐75], Opening pressure 18 mm CSF [70‐180 mm H2O], Total proteins 86 mg/dL [15‐45], Rapid plasma regain ‐Negative, Lyme serology Negative
Which of the following is the most likely diagnosis?
(A) Meningococcal meningitis
(B) Tick‐borne encephalitis
(C) Lyme encephalitis
(D) Typhoid fever
(E) Brill‐Zinsser disease ( Recrudescent typhus fever )
Ans B • Tick‐borne encephalitis is endemic in Northern, Central, and Eastern Europe and includes such countries as Austria and Germany.
• It is transmitted by the Ixodes tick and by the ingestion of unpasteurized dairy products. It is a flavivirus and related to yellow fever, West Nile virus, Japanese encephalitis virus, and dengue. • After an incubation period of one to two weeks, a biphasic illness ensues. The first phase is a self‐limited nonspecific "viral" illness. • Most patients remain well, but up to a third have a second phase characterized by recrudescence of fever associated with central nervous system signs and symptoms. • Meningococcal meningitis is a very unlikely cause of this patient's illness given that she has not traveled to an endemic area, the high likelihood that as a college student she has been vaccinated, and the spinal fluid formula. • Although Lyme encephalitis is a possible answer, meningitis is a more common central nervous system (CNS) involvement, and the biphasic illness along with the negative serology makes this less likely. • Typhoid fever can be associated with CNS disease, but this patient's case is not typical for that illness, and she did not travel to high‐risk places. Brill‐Zinsser disease is a recrudescent epidemic typhus. She does not have a history that would suggest the likelihood of a previous episode of typhus, and she has no rash. 4
• Five months ago, a 36‐year‐old woman had a 7‐cm erythematous rash on her right flank and fevers to 38.3 C (101.0 F). She was noted to have erythema migrans and was given a diagnosis of Lyme disease, although her serology was negative. She was treated with doxycycline, 100 mg twice daily for 14 days. Her rash and fevers improved over 48 hours, and she was well until two days ago, when she again had fever without other symptoms. Her husband noted an erythematous patch on her back. The rash was painless. • On physical examination today, the patient appears well and physically comfortable, although she is concerned about the rash. A slightly sensitive, homogeneous, erythematous patch is present on the right scapula. Two slightly smaller but similar lesions are seen on the left buttock. The lymph nodes are not enlarged. Serology is positive for Lyme disease. Which of the following is the most appropriate treatment for this patient now?
A) Doxycycline for ten to 21 days for a new infection
(B) Doxycycline for six weeks for a relapse
(C) Azithromycin for 21 days for a relapse
(D) Ceftriaxone for 14 days for a relapse
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Ans A
• It is of concern that Lyme disease (LD) frequently relapses, and such relapses may require a more prolonged course of therapy for the residual focus of infection. Studies of persons who have had more than one episode of documented LD have shown that repeated episodes are reinfections rather than relapses; therefore, these episodes should be treated like the initial episode, and the patient should be treated with doxycycline for ten to 21 days. For those who cannot take doxycycline, amoxicillin or cefuroxime can be substituted. Because most people who live in Lyme disease endemic areas are at risk for re‐exposure, this finding is not reassuring, but it also is not surprising. The risk of acquiring Lyme disease can be decreased with the regular use of diethyltoluamide (DEET)‐
containing insect repellents, protective clothing, and frequent tick checks. 5
• A 21‐year‐old student is leaving in one week to spend the summer hiking and camping in Austria, Germany, and Switzerland. She is concerned about tick‐borne encephalitis (TBE) and asks your advice about decreasing her risk for acquiring the disease.
• Which of the following is the best advice for lowering the risk for tick‐borne encephalitis?
(A) Use insect repellent containing DEET (diethyltoluamide n,n‐diethyl‐m‐
toluamide)
(B) Take a single dose of doxycycline after exposure
(C) Obtain yellow fever vaccination for cross‐protection because TBE and yellow fever are both flaviviruses
(D) No concern is necessary because the countries on the itinerary have no risk factors
Ans A • The incidence of tick‐borne encephalitis (TBE) is increasing and can be found in much of Northern, Central, and Eastern Europe, including the countries on this woman's itinerary. TBE is transmitted by the Ixodes tick (and, occasionally, by unpasteurized milk products). Bed netting might provide a small benefit, but ticks are more likely to be acquired during the day. The best way to prevent tick bites is to use an insect repellent containing DEET. Although doxycycline may provide some benefit in preventing Lyme disease acquired from an Ixodes tick bite, it is not beneficial for preventing the transmission of the virus that causes TBE. There is an effective vaccine for TBE that is available in Canada and in Europe, but it is not licensed in the United States. Although yellow fever and TBE are both caused by flaviviruses, there is no evidence of benefit from the former in preventing the latter, and there is increasing concern about yellow fever viscerotropic disease, which is a serious adverse effect of the yellow fever vaccine.
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Babesia
•
•
•
•
•
Intra RBC protozoan
Ixodes tick from rodents
Nantucket in summer/fall
Fever, sweats, myalgia, chills
The parasites are pleomorphic (vary in shape and size), can be vacuolated, and do not produce pigment.
• The tetrad, a dividing form pathognomonic for Babesia
• The clumped extra cellular forms indicative of Babesia
• Rx: clindamycin + quinine or atovaquone + azithromycin
Ehrlichia
• Ehrlichia chaffeensis : monocytes
• Tick borne • Spotless fever
• Flu like symptoms
• Pancytopenia
• Dx : morula on smear
• Tx : doxycycline
• Human granulocytic ehrlichiosis: neutrophils
RMSF
• RMSF is a tick‐borne rickettsial infection.
• In the United States, RMSF is most prevalent in the southeastern and south central states. • Look for a history of tick bite and recent travel to an endemic area; febrile illness in spring and summer months; and nonspecific symptoms such as nausea, myalgia, dyspnea, cough, and headache. • Also look for a macular rash starting on the ankles and wrists; lesions spread centripetally and become petechial. Thrombocytopenia and elevated aminotransferase levels are characteristic. • Select indirect fluorescent antibody assay to make the diagnosis.
• Select doxycycline. In patients who are pregnant, choose chloramphenicol.
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You are evaluating a 32‐year‐old man who has recently received a diagnosis of HIV infection. He feels well, and his physical examination reveals no abnormalities. His CD4 lymphocyte count is 254/mcL [530‐1570], and his HIV viral load is 76,000 copies/mL [less than 400]. He has no genotype resistance. You begin treatment with tenofovir, emtricitabine, and a booster of atazanavir. You discuss with the patient the potential adverse effects of these antiretroviral (ART) medications. In your discussion of potential ART adverse effects, which of the following should be mentioned to the patient regarding atazanavir?
A Altered mental status
B Kidney stones
C Lactic acidosis
D Intracranial hemorrhage
E. Pulmonary fibrosis
Ans B • In general, atazanavir is well tolerated, with a low incidence of adverse reactions. The most common adverse effect is hyperbilirubinemia. • Although this laboratory abnormality is seen in most patients taking the drug, it is not associated with hepatobiliary symptoms, and only when significant jaundice becomes a cosmetic issue does the drug have to be discontinued. • Recently, the association of atazanavir with nephrolithiasis due to precipitation of the drug in the kidneys has been noted, and occasionally this drug can result in an elevated level of serum creatinine
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• You are treating a 50‐year‐old man who recently received a diagnosis of HIV infection. One month ago, his CD4 lymphocyte count was 450/mcL [530‐1570], and his viral load was 55,000 copies/mL [less than 400]. His genotype showed wild‐type virus. He had diet‐
controlled diabetes mellitus but no other comorbidities. He was taking no regular medications. After reviewing the options for therapy, you prescribed a single‐tablet regimen of elvitegravir‐cobicistat‐emtricitabine‐tenofovir (Stribild). At followup today, the patient's CD4 lymphocyte count is 550/mcL, and his viral load is 280 copies/mL. His serum creatinine has increased from 0.79 mg/dL [0.7‐1.5] to 0.96 mg/dL. • Which of the following is most likely to have effected this change in serum creatinine?
• (A) Renal tubular toxicity of tenofovir
• (B) Decreased proximal tubular secretion of serum creatinine by cobicistat
• (C) Worsening of glycemic control by elvitegravir
• (D) Interference with laboratory reagents by one of the components
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Ans B
• Cobicistat is a pharmacoenhancer, or boosting agent, which functions as a potent inhibitor of cytochrome P450 3A. In this setting, it is used to maintain levels of elvitegravir. • In clinical trials with this agent, small increases in serum creatinine were consistently seen. The mechanism for these increases has been determined to be a reversible inhibition of a tubular secretion of creatinine by cobicistat. • This shows up as the difference in the estimated but not the actual glomerular filtration rate, which is not of clinical significance. Although this individual could have toxicity from tenofovir, it is less likely, particularly so early in therapy, and the degree of creatinine increase is within the range described for cobicistat. • An increase in creatinine of greater than 0.4 mg/dL above baseline has been proposed to distinguish the effect of cobicistat from genuine renal dysfunction. Elvitegravir has no effect on glycemic control, nor do any of the components of a single‐tablet regimen consisting of tenofovir, emtricitabine, elvitegravir, and cobicistat (Stribild) interact with laboratory reagents used to monitor kidney function. Common ART Side Effects
NRTIs
Zidovudine
Side Effects
Anemia, neutropenia, and myopathy
Didanosine
Peripheral neuropathy and pancreatitis
Stavudine
Peripheral neuropathy, lactic acidosis, and fat atrophy
Abacavir
Hypersensitivity reaction (with or without rash)
Tenofovir
NNRTIs
Nevirapine
Kidney dysfunction
Side Effects
Rash (including Stevens‐Johnson syndrome) and hepatotoxicity
Mood or psychiatric alterations, vivid dreams, or hallucinations
Side Effects
Hyperlipidemia, pancreatitis, fat distribution, and insulin resistance
Same as for other protease inhibitors, plus kidney stones, kidney insufficiency, and elevated indirect bilirubin
Efavirenz
Protease Inhibitors
Saquinavir, ritonavir, nelfinavir, and tipranavir
Indinavir
Atazanavir
Increased indirect bilirubin
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A 42‐year‐old man has had relapsing Crohn's disease since he was 21 years old. His relapses have been characterized by abdominal cramping, fevers, and several perianal fistulous tracks. His latest relapse, which occurred about one year ago, was
initially poorly controlled with high‐dose corticosteroids, and he lost approximately 18 kg (40 lb). Eight months ago, he began taking natalizumab and achieved good control of his symptoms. Four months ago, he was able to taper off his corticosteroid medication. He regained his lost weight, and his fistulas closed. Two weeks ago, however, the patient noted parasthesias in his right cheek. Over the course of the following week, he progressively lost the ability to speak. He has not had fever, headache, or visual problems. He takes no other medications. The patient is an elementary schoolteacher, and he has had negative reactions to annual tuberculin skin tests for the past 20 years.
He has traveled to Europe several times, and he spends his summers in Key West, Florida. On physical examination, the patient is awake and alert, with moderate expressive aphasia and a right plantar extensor reflex. Temperature is 37.3 C (98.2 F), pulse rate is 72 per minute, respirations are 14 per minute, and blood pressure is 125/75 mm Hg.
The fundi are normal. No enlargement of lymph nodes, liver, or spleen is noted, and no heart murmur is present. Hemoglobin 12.6 g/dL [14‐18], Leukocyte count 4500/mcL [4000‐11,000], Serum alanine aminotransferase 22 U/L [10‐40], Serum creatinine 1.1 mg/dL [0.7‐1.5], HIV test Negative , Lumbar puncture, Cell count 2 WBCs/mcL (100% [30‐45] lymphocytes), 3 RBCs/mcL [cell count 0‐5]
Glucose 80 mg/dL [50‐75], Opening pressure 12 mm , Total proteins 43 mg/dL [15‐45]
Magnetic resonance imaging of the brain reveals a single demyelinating lesion in the left parietotemporal region. Which of the following tests of the CSF is most likely to yield the correct diagnosis?
(A) Bacterial culture
(B) PCR for herpes simplex virus 1
(C) IgM for West Nile virus
(D) Ultrasensitive PCR for JC virus
(E) Evaluation for oligoclonal bands
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Ans : D.
• Progressive multifocal leukoencephalopathy (PML) has been associated with monoclonal antibody therapy such as natalizumab. PML manifests typical subacute neurologic deficits that can vary depending on which area(s) of the brain are involved. Unlike other manifestations of PML, natalizumab‐associated PML is more likely to show gadolinium enhancement on MRI and is more likely to be univocal on presentation. Ultrasensitive PCR testing for JC virus in the CSF is greater than 95% sensitive. This patient does not have meningitis; therefore, bacterial culture of the CSF is unlikely to be diagnostic. Herpes simplex virus infection typically has a more acute onset, involves the temporal lobes, is associated with high fevers, and enhances on magnetic resonance imaging. West Nile encephalitis is a possible choice, but the single white matter lesion and normal CSF would be highly atypical. An initial presentation of multiple sclerosis is difficult to exclude, but the patient has a single white matter lesion, making PML a better choice. 9
• HIV‐2, a lentivirus in the same genus as HIV‐1, has a number of clinically significant differences that must be recognized by a clinician in order to provide proper care for a patient infected with HIV‐2. • In which of the following features does HIV‐2 differ from HIV‐1?
• (A) HIV‐2 is often missed on a standard HIV ELISA screening test
• (B) Efavirenz is predictably ineffective against HIV‐2
• (C) Approximately 20% of individuals infected with HIV‐2 are long‐
term nonprogressors
• (D) HIV‐2 is more easily transmissible than HIV‐1
Ans B
• HIV‐2 is resistant to non‐nucleoside inhibitors. HIV‐1 and HIV‐2 are closely related retroviruses. Both arose from the introduction of simian immunodeficiency virus (SIV) into humans; HIV‐1 from SIVcpz (chimpanzees) and HIV‐2 from SIVsm (sooty mangabeys). They are transmitted in a similar fashion, but SIV has a much slower rate of progression, with approximately 90% of people infected with HIV‐2 becoming long‐term nonprogressors. Most cases of HIV‐2 infection have been traced to contact with someone from West Africa. The screening tests for HIV‐
1/HIV‐2 identify both viruses but do not distinguish between them; therefore, some cases of HIV‐2 infection may be misdiagnosed as HIV‐1 infection. HIV‐2 infection should be considered when the HIV‐1/HIV‐2 screening tests are positive, but confirmation by Western blot yields an intermediate or nonreactive result. HIV‐1 can be excluded by RNA testing, in which case an HIV‐1/HIV‐2 type differential immunoassay should be performed. HIV‐2 is resistant to non‐nucleic reverse transcriptase inhibitors, including efavirenz. 8
4/20/2015
Prophylaxis for Patients with HIV Infection
Preventable Condition
When
Agent
P. jirovecii pneumonitis
CD4 cell count <200/µL
Trimethoprim‐sulfamethoxazole
Toxoplasmosis
CD4 cell count <100/µL and positive IgG for toxoplasmosis
Trimethoprim‐sulfamethoxazole
Mycobacterium avium complex infection
CD4 cell count <50/µL
Azithromycin
Active or latent TB
TST ≥5 mm induration
Influenza
Annual vaccination for all HIV‐
infected patients
Killed influenza vaccine
Pneumococcal pneumonia
Vaccination every 5 to 10 years for all HIV‐infected patients
Pneumococcal vaccine
Hepatitis A and B
One‐time vaccination
Hepatitis A and B vaccine
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11
A 55‐year‐old man is referred to you for treatment of a prosthetic knee infection. He underwent joint replacement for degenerative disease one month ago, and, for the past week, he has had progressive swelling and joint pain. A culture obtained from an outpatient aspiration procedure grew coagulase‐negative staphylococci with in vitro susceptibility to vancomycin, daptomycin, doxycycline, and rifampin. Before coming to you for consultation, the patient was taken to the operating room, where he underwent surgical debridement of the joint. The prosthesis was noted to be well fixed, without any loosening. The liners were replaced, and the original prosthesis was retained. Which of the following treatment regimens should be recommended for this patient now?
(A) Daptomycin for six weeks
(B) Vancomycin and rifampin for six weeks
(C) Vancomycin for two weeks followed by doxycycline for four weeks
(D) Intravenous vancomycin for six weeks followed by doxycycline and rifampin for 18 weeks
Ans D
• This patient fits the criteria for debridement and retention of his joint prosthesis. He is within 30 days of prosthesis implantation and less than three weeks from the onset of symptoms. Moreover, he has a relatively low‐grade pathogen. • The guidelines recently published by the Infectious Diseases Society of America support the use of rifampin in the treatment of prosthetic joint infections. • They recommend two to six weeks of pathogen‐specific intravenous therapy, followed by rifampin with an oral "companion drug" for a total of six months for infected total knee arthroplasty. • Continuing beyond six months does not seem to increase the likelihood of cure, but stopping earlier puts the patient at risk for relapse. Only one of the proposed regimens meets the criteria stated in the guideline.
Study Table:Categorization and Characterization of Osteomyelitis
Category
Characteristics
Acute hematogenous osteomyelitis
Infection of intervertebral disc space and two adjacent vertebrae
Contiguous osteomyelitis
Patients >50 years old with diabetes mellitus or peripheral vascular disease and a foot ulcer
Following dog or cat bite
Pasteurella multocida may cause contiguous‐
focus osteomyelitis after dog or cat bites
Following foot puncture wound
Pseudomonas is frequently isolated following puncture wounds through the rubber sole of a shoe.
Sternal osteomyelitis
Wound healing complications, unstable sternum, and fever after thoracic surgery
Clavicular osteomyelitis
Pain, cellulitis, or drainage after subclavian vein catheterization
Pain and fever in an injection‐drug user
Sternoclavicular joint osteomyelitis
Sickle cell disease
Bone infarcts and bone marrow thrombosis predispose to osteomyelitis most commonly caused by Salmonellaspecies and S. aureus.
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• A 60‐year‐old man is admitted to the hospital because of left lower leg cellulitis. This is his third such episode in the past 18 months. He is not obese, has no history of trauma to his legs, and has never had leg surgery. He has venous insufficiency and wears elastic stockings on most days to reduce the likelihood of swelling. He also has type 2 diabetes mellitus, hypertension, and hyperlipidemia, all of which are well controlled by medical therapy. The patient responds well to parenteral antibiotic therapy. As with his previous episodes of cellulitis, bacterial cultures are negative. Before his discharge, the patient asks you to recommend other interventions to prevent recurrence of his cellulitis. • Which of the following prophylactic medications should be recommended for this patient now?
A) Doxycycline, 100 mg twice daily
(B) Extra‐strength trimethoprim‐sulfamethoxazole once daily
(C) Intranasal mupirocin for five days
(D) Penicillin VK, 250 mg twice daily
Ans D
• Beta‐hemolytic streptococci have been identified as the major pathogen in approximately 70% of cases of cellulitis without purulence. In a patient such as this, who has had recurrences, presumably on the basis of lymphedema, the percentage attributable to streptococcal infection is likely higher. In the United Kingdom, Thomas and colleagues carried out a randomized, double‐blind trial in patients who had experienced two or more episodes of cellulitis of the legs. They found that over a 12‐month treatment interval, the frequency of recurrence was reduced by approximately 50%. This benefit was lost after 36 months. Neither doxycycline nor trimethoprim‐sulfamethoxazole would be expected to be active in preventing streptococcal infections. Because colonization with beta‐hemolytic streptococci is not intranasal, mupirocin would not be expected to be active either.
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• A 30‐year‐old man is evaluated for treatment of cellulitis. He reports that he fell off his bicycle and scraped his leg three days ago. On physical examination, he appears well and has no fever. A tender and erythematous area with a diameter of approximately 10 cm is noted on his right lateral calf. No lymphangitis is present. The patient has no comorbidities and has had no unusual exposures. He has no allergies. He works as an attorney. • Which of the following is the most appropriate antibiotic therapy for this patient?
(A) Doxycycline
(B) Cephalexin
(C) Trimethoprim‐sulfamethoxazole and penicillin VK
(D) Clindamycin
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Ans B
• For outpatients who have nonpurulent cellulitis, the clinical practice guideline of the Infectious Diseases Society of America (IDSA) for treatment of MRSA infections recommends empiric therapy for infection caused by beta‐hemolytic streptococci. Empiric coverage for MRSA is recommended only for patients who do not respond to beta‐lactam therapy. The recommendation is based on the fact that an estimated 70% of nonpurulent soft tissue infections in this population are attributable to beta‐hemolytic streptococci. Despite this recommendation, many patients seen in emergency departments in the United States for soft tissue infections are given therapy directed against MRSA or antibiotics for both MRSA and streptococci. Pallin and colleagues carried out a randomized, multicenter, double‐blind, placebo‐controlled trial to determine whether treatment for MRSA was advantageous in this population. They found that the addition of trimethoprim‐sulfamethoxazole to cephalexin did not improve outcomes. This was true in patients with and without purulence and whether or not the patients were colonized with MRSA. It is hoped that this study will reinforce the appropriateness of the IDSA guideline for empiric antibiotic therapy of uncomplicated cellulitis (SSTI). Doxycycline does not have reliable activity against beta‐hemolytic streptococci. A double antibiotic regimen (trimethoprim‐
sulfamethoxazole and penicillin) is not necessary. Clindamycin may be appropriate in the setting of beta‐lactam allergy, but increasing resistance of beta‐hemolytic streptococci to this agent is being reported, whereas none is reported to penicillin and cephalexin.
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• During the past month, a 36‐year‐old man has had a low‐grade fever, a cough that is occasionally productive of sputum, and a 17‐kg (8‐lb) weight loss. He used injection drugs when he was in his 20s, but he completed a rehabilitation program and has not used injectable drugs for seven years. Recently, he completed a prescribed course of azithromycin with no improvement of symptoms. • The patient is thin, and he coughs during the physical examination. Temperature is 37.7 C (99.8 F), pulse rate is 88 per minute, respirations are 18 per minute, and blood pressure is 124/72 mm Hg. Lymph nodes are not enlarged. The chest is clear to auscultation, and the heart has no murmur or gallop. The abdomen is soft and nontender with no liver or spleen enlargement. No rash or edema is noted. • After starting antimycobacterial therapy, which of the following would be the best time to introduce antiretroviral therapy?
A) Within two weeks
(B) Between two and four weeks
(C) After completion of antituberculous therapy
(D) Approximately eight weeks
Ans : D
• Choosing the best timing for introduction of antiretroviral therapy after starting antituberculous therapy in patients who have HIV infection and newly diagnosed tuberculosis involves balancing the risk of death and progression to AIDS versus the risk of immune reconstitution inflammatory syndrome (IRIS). A study in 2010 showed that delaying antiretroviral therapy (ART) until after completion of treatment for tuberculosis led to higher mortality. Three clinical trials published in the October 20, 2011 edition of The New England Journal of Medicine attempted to more finely determine the best timing for ART. Taken together, these studies showed that the lower the patients CD4 lymphocyte count, the greater the risk for progression to AIDS or death when ART was not administered immediately. The effect appeared to be critical in those patients who had CD4 lymphocyte counts consisting of fewer than 50 cells. In patients who had CD4 lymphocyte counts greater than 50 cells, delaying ART until approximately two months after initiation of antimycobacterial
therapy did not affect mortality or progression to AIDS and was associated with fewer problems with IRIS. One important proviso, however, is that patients with certain forms of extrapulmonary tuberculosis, notably tuberculous meningitis, have been shown to be susceptible to severe morbidity and mortality when ART is administered very early in the course of treatment. It is generally advisable to wait approximately eight weeks before starting ART in these patients, even if they have fewer than 50 CD4 lymphocyte cells. The patient described here has relatively uncomplicated pulmonary tuberculosis and a CD4 lymphocyte count of greater than 50 cells; therefore, it would be best to initiate ART approximately eight weeks after starting antituberculous therapy.
•
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• 59 yo homeless man with history of EtOH abuse with 2 weeks of fever and cough
• PPD positive at 19 mm
• Chest film reveals….
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Postprimary pulmonary TB
• Asymmetric process of the lungs involving caseation, cavity formation, and fibrosis
• Predominantly in the subapical portion of the upper lobes
• Associated fever, chills, NS, malaise, anorexia, and weight loss
• TEST ALL PTS WITH TB FOR HIV
Treatment principles for TB
• 4 drugs are preferred, 3 are acceptable if INH resistance is less than 4%
• Test all isolates for drug susceptibilities
• Response to therapy must be documented with monthly repeat sputum cxs until conversion
• 85% of pts will convert their cxs by 2 mos
• If pt is not responding by 4 weeks, add 2 drugs
• Extrapulmonary disease may require longer therapy
• Steroids only for meningitis and pericarditis
17
Which of the following findings would most likely contraindicate
treatment of this patient with bedaquiline?
(A) Nephrotic syndrome
(B) Leukopenia related to HIV infection
(C) Compensated hepatitis C virus infection
(D) History of cardiac arrhythmia on treatment
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Ans : D
• Bedaquiline (TMC207) was given fast‐track approval by the Food and Drug Administration because it is active against resistant strains of Mycobacterium tuberculosis and was shown in phase II studies to be able to sterilize sputum faster than placebo when added to a multidrug regimen. Bedaquiline also has been shown to help prevent development of resistance to companion drugs in multidrug regimens. Studies large enough to show a definite clinical benefit have not yet been completed. For now, the primary use of bedaquiline is in management of multidrug‐resistant tuberculosis. The compound has a unique mechanism of action, which is to inhibit mycobacterial adenosine triphosphate (ATP) synthase. Over time, bedaquiline is thought to starve the mycobacterial cell of energy, leading to cell death. The drug has strong selectivity for mycobacterial ATP synthase over mammalian ATP synthase. The drug has a very long half‐life (5‐6 days). It is metabolized by the CYP450 system, and the area under the curve (AUC) when used with rifampin is about 50% of normal AUC; however, it has performed well in small studies when used with rifampin. The approved dose is 400 mg once daily for 14 days, then 200 mg three times weekly until 24 weeks of treatment are completed. Bedaquiline
can cause prolongation of the QT interval, and there is a black box warning concerning use of the drug in patients who have preexisting QT interval prolongation or who are on other drugs that prolong the QT interval. Also, in one of the trials, there was a higher death rate in patients receiving bedaquiline, but all but one of the deaths occurred after bedaquline had been discontinued, making a causal association with the drug seem unlikely. However, the approval of the drug with only surrogate endpoints was not without controversy, as shown by the last cited reference. The drug does not cause bone marrow depression, and it can be used safely in patients with mild to moderate renal dysfunction. Bedaquiline can cause elevation of liver function tests, but, if liver function is monitored, the drug appears to be safe in patients who have mild hepatic disease.
18
• During an annual screening for tuberculosis, a 30‐year‐old nurse is newly found to have a positive response to a tuberculin test. She is initially reluctant to undergo treatment for latent tuberculosis, but she agrees to accept therapy if you can provide a regimen that uses a minimum number of doses over the shortest possible time. • Which of the following treatment regimens for latent tuberculosis is most appropriate for this patient?
• (A) Isoniazid
• (B) Rifampin
• (C) Rifampin and pyrazinamide
• (D) Isoniazid and rifapentine
• (E) Azithromycin
Ans D
• For prevention of tuberculosis, a once weekly regimen of isoniazid, 900 mg, and rifapentine, 900 mg, given for 12 weeks, has proved to be as effective as isoniazid alone for nine months. To date, this combination regimen has not been shown to cause any increase in toxicity. When given as directly observed therapy, this regimen had a higher completion rate in trials than that of standard daily isoniazid. The two‐month regimen of rifampin and pyrazinamide given daily was associated with significantly more hepatotoxicity and is not recommended. Although azithromycin can be used as prophylaxis and treatment for Mycobacterium avium‐complex, it has no activity against M. tuberculosis.
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Screening for latent TB
•
•
•
•
•
•
•
•
•
•
Screening
Select TST using PPD for all patients at high risk of exposure to TB, including:
those with close contact to a person known or suspected to have TB
recent immigrants from countries with a high prevalence of TB (Asia, Africa, Latin America, Eastern Europe, and Russia)
health care workers who care for clients at high risk
medically underserved, low‐income populations
injection drug users
persons who have been incarcerated
those with a medical condition that increases the risk of active TB, including HIV
Another screening option is the IGRAs, which are more specific than TST for the diagnosis of active and latent TB infection (LTBI) and may be used for the same indications as TST; although more expensive, IGRAs are increasingly being used in place of the TST.
Study Table:Interpretation of Tuberculin Skin Test Results
Criteria for Tuberculin Positivity by Risk Group
≥5 mm Induration
≥10 mm Induration
≥15 mm Induration
Persons who are HIV positive Recent (<5 yr) arrivals from high‐
All others with no risk factors prevalence countries
Recent contacts of persons for TB
Injection drug users
with active TB
Residents or employees of high‐risk Persons with fibrotic changes congregate settings: prisons and jails, on chest x‐ray consistent with nursing homes and other long‐term facilities for older adults, hospitals old TB
Patients with organ transplants and other health care facilities, residential facilities for patients with and other immunosuppressive AIDS, homeless shelters
conditions (receiving the Mycobacteriology laboratory equivalent of ≥15 mg/d of personnel; persons with clinical conditions that put them at high risk prednisone for >4 weeks)
for active disease; children aged <4 years or those exposed to adults in high‐risk categories
19
• The annual incidence of HIV infection in the United States has not significantly decreased during the past decade. One response to this lack of improvement has been the new United States Preventive Services Task Force's (USPSTF) recommendation for HIV screening.
• Which of the following groups best characterizes the most recent USPSTF recommendations for HIV screening?
(A) All men who have sex with men regardless of age
(B) All pregnant women
(C) All persons aged 15‐65 regardless of acknowledged or perceived risk factors
(D) All persons aged 15‐45
(E) All adolescents and adults aged 15‐65 at increased risk for infection
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Ans : C
• The estimated prevalence of HIV infection in the United States is 1.2 million, with an annual incidence of 50,000. Nearly 25% of those infected with HIV are unaware of their status and represent a large reservoir for HIV transmission. In addition, data supporting the benefit of treatment in individuals who have higher CD4 lymphocyte counts (up to 500) and the benefit of treatment as a means of decreasing transmission from persons regardless of their CD4 lymphocyte cell count has added to the potential benefits of screening the entire population regardless of acknowledged or perceived risk factors. The updated recommendations now suggest screening for all adults and adolescents aged 15‐65 years as well as younger adolescents or older adults at risk.
20
• A 29‐year‐old man who underwent resection of a glioblastoma multiforme tumor subsequently relapsed with recurrent tumor in the operative bed. He has been treated with radiation, dexamethasone, and temozolomide for relapsed disease and is completing his sixth week of therapy. He is evaluated now because for the past ten days he has had progressive shortness of breath, fever, and dry cough. • The patient appears slightly ill and speaks in short sentences. Temperature is 38.3 C (101.0 F), pulse rate is 100 per minute, respirations are 20 per minute, blood pressure is 110/60 mm Hg, and oxygen saturation is 90% at rest on room air. Chest examination is significant for mild crackles throughout both lung fields.
A) High‐dose trimethoprim‐sulfamethoxazole and corticosteroids
(B) Intravenous acyclovir
(C) High‐dose azithromycin
(D) Voriconazole
(E) Liposomal amphotericin B
Ans A • The historic features and clinical picture in this case are suggestive of Pneumocystis jiroveci
pneumonia (PCP); therefore, trimethoprim‐sulfamethoxazole and corticosteroids would be the most appropriate empiric therapy. • Temozolomide is associated with lymphopenia, and thus opportunistic infection with PCP in particular has been seen. Patients are at higher risk for disease after long duration of therapy in conjunction with radiation and corticosteroids. • The recommendation is to give PCP prophylaxis to those receiving temozolomide and radiation and to continue prophylaxis until lymphocyte recovery. • CMV disease also has been reported in patients on temozolomide, and reactivation of other herpesvirus infections would certainly seem plausible as well, although the history of this patient is more consistent with PCP than a herpesvirus that would prompt acyclovir therapy. • High‐dose azithromycin would be appropriate for Legionella infection, which has been seen in patients on temozolomide; however, given this patient's history, this is less likely. Fungal infections that would be treated with voriconazole or amphotericin also would be less likely in this case.
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21
• A 48‐year‐old man who has rheumatic mitral stenosis was doing well until he had fever, malaise, and anorexia that persisted for ten days. He saw his primary care physician, who noted a new mitral regurgitant
murmur. The patient was admitted to the hospital, and blood cultures were obtained. • On admission, the patient appeared well and was lying comfortably in a supine position. Temperature was 38.2 C (100.8 F), pulse rate was 84 per minute, respirations were 14 per minute, and blood pressure was 130/60 mm Hg. No conjunctival petechiae were seen, but several splinter hemorrhages were noted. Jugulovenous distention was present to 6 cm above the clavicle at 30 degrees, a left ventricular impulse was noted at the midclavicular line, a grade 2/6 early diastolic rumble was heard, and a grade 3/6 holosystolic
murmur radiating to the left axilla was audible at the apex. The liver and spleen were not enlarged. • Four blood cultures were obtained, all of which grew alpha‐hemolytic streptococci with a minimum inhibitory concentration of 0.06. A transesophageal echocardiogram revealed a 1.2‐cm vegetation on a posterior leaflet of the mitral valve, with severe valve dysfunction but no evidence of heart failure. Follow‐up blood cultures have been negative. The treatment plan for the patient is penicillin, 18 million units daily for four weeks. Which of the following is the most appropriate additional management strategy at this time?
(A) Delay surgical removal of the vegetation until two weeks after completion of antibiotic therapy
(B) Delay surgical removal of the vegetation until completion of the antibiotic course
(C) Add a second antibiotic for synergy
(D) Delay surgical removal of the vegetation unless a complication occurs
(E) Suggest early surgical removal of the vegetation
Ans E
• In patients who have left‐sided infective endocarditis with a vegetation larger than 10 mm, a prospective randomized trial looked at early surgery versus surgery after a complication requiring surgery. Embolic events and death were statistically lower in the early surgery group versus the delayed surgery group. At six months, all‐cause mortality did not differ in the two groups, but occurrence of embolic events, hospital admissions for congestive heart failure, and recurrence of endocarditis was 3% in the early surgery group and 23% in the delayed group (P = 0.02). There is no study that addresses the question of surgery after two weeks of antibiotic therapy. In patients who have streptococcal endocarditis with a low minimum inhibitory concentration organism, synergistic treatment does not provide additional benefit.
• For further information, see the following:
Endocarditis • Risk factors for IE include injection drug use and the factors listed above. Fever, malaise, and fatigue are sensitive but nonspecific symptoms associated with IE. Suggestive physical examination findings include:
• new cardiac murmur
• new‐onset HF
• conduction abnormalities on ECG (suggests perivalvular abscess)
• focal neurologic signs (septic emboli)
• splenomegaly
• petechiae, splinter hemorrhages
• Osler nodes (violaceous, circumscribed, painful nodules found in the pulp of the fingers and toes)
• Janeway lesions (painless, erythematous, macular lesions found on the soles and palms)
• Roth spots (hemorrhagic lesions of the retina)
• leukocytosis, anemia, and hematuria
• multiple bilateral small nodules on chest x‐ray (septic emboli)
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Osler nodes are red to purple painful papules, papulopustules, or nodules found in the pulp of fingers or occasionally hands and feet and seen in cases of IE. Janeway lesions are macular, erythematous, nontender microabscesses
in the dermis of the palms and soles caused by septic emboli that are considered pathognomonic for IE. Septic pulmonary emboli
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Diagnosing Endocarditis
Major Duke Criteria
Minor Duke Criteria
Positive blood culture for endocarditis ×2
Predisposing heart condition or injection drug use
Positive echocardiogram
Fever
New valvular regurgitation
Embolic vascular phenomena
Immunologic phenomena (glomerulonephritis or rheumatoid factor)
Positive blood culture not meeting major criteria
Endocarditis
• Select a transthoracic echocardiogram (TTE) for all patients with bacteremia. In patients with high clinical suspicion of IE but normal TTE, obtain a TEE, particularly in the setting of S. aureus bacteremia. TEE is the test of choice to identify a paravalvular abscess.
• Apply the “modified for easy memory” Duke Criteria (below) to diagnose endocarditis. Diagnose endocarditis in patients with two major criteria or one major and three minor criteria.
• HACEK organisms (Haemophilus aphrophilus; Actinobacillus
actinomycetemcomitans; Cardiobacterium hominis; Eikenella corrodens; and Kingella kingae), previously associated with “culture‐negative” endocarditis are now easily isolated when incubated for at least 5 days. Prophylaxis is only indicated for the highest risk procedures:
• dental procedures that involve mucosal bleeding
• procedures that involve incision or biopsy of the respiratory mucosa
• procedures in patients with ongoing GI or GU tract infection
• procedures on infected skin, skin structures, or musculoskeletal tissue
• surgery to place prosthetic heart valves or prosthetic intravascular or intracardiac materials
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Provide prophylaxis for IE only in patients with the highest risk
• prosthetic heart valves or valve repair with prosthetic material
• previous endocarditis
• congenital heart disease
• unrepaired cyanotic congenital heart disease
• palliative shunts and conduits
• prosthetic valve
• repair with prosthetic material or device for the first 6 months after intervention
• valve disease in heart transplant recipients
22
• You are evaluating a 48‐year‐old woman who was injured when a tornado swept through her town one week ago. She has been in the intensive care unit because she sustained a 12x18‐cm (5x7‐in) wound on her right thigh and a 9x7‐cm (4x3‐in) wound on her left thigh. The wounds were initially debrided, and cultures were obtained, which grew only coagulase‐negative Staphylococcus. The patient also had renal failure and has been receiving continuous dialysis. She is on a respirator because she had blunt chest trauma and a lung contusion. She has not had changes in blood pressure, oxygenation, or pressor requirements. • The patient is sedated and on a ventilator. Temperature is 37.2 C (98.9 F), pulse rate is 102 per minute, respirations are 18 per minute, and blood pressure is 104/68 mm Hg. Oxygen saturation is 95% on 40% FIO2. Physical examination is focused mainly on the leg wounds, which have black patches in the subcutaneous tissue and exposed muscle with minimal drainage. Mild erythema is present at the wound margins. She is being treated with piperacillin‐tazobactam and vancomycin.
• Labs : Hematocrit 31% , Leukocyte count 13,740/mcL , 88% neutrophils, 8% lymphocytes, 4% monocytes,Platelet count 389,000/mcL ,Serum creatinine 1.87 mg/dL , on dialysis
• A tissue biopsy and bacterial, mycobacterial, and fungal cultures of the wounds are pending.
• Until results of the ordered tests become available, which of the following would be the most appropriate addition to this patient's treatment regimen?
(A) Voriconazole
(B) Trimethoprim‐sulfamethoxazole
(C) Clarithromycin
(D) Replacement of vancomycin with daptomycin
(E) Liposomal amphotericin B
Ans E • Thirteen cases of invasive mucormycosis that occurred in large traumatic wounds were reported after injuries sustained in an EF‐5 (greater than 200 miles per hour) tornado that passed through a town in Missouri. The identified species was Apophysomyces trapeziformis. The infections were identified between six and 24 days after the initial injuries, and, in most cases, the wounds had already undergone initial debridement. After diagnosis, the patients required a mean of four additional surgical debridements. The overall mortality was high (38%). This report did not represent an isolated incident, as mucormycosis and Apophysomyces infections have previously been described in traumatic wounds after natural disasters, although not in such large numbers of patients. Given the high mortality, it makes sense to initiate treatment pending the results of biopsy and cultures, which might require a few days. The other possible additions to therapy are not as satisfactory. Voriconazole therapy might be a good choice if Aspergillus or another voriconazole‐susceptible infection had caused the necrosis, but it would not cover Mucorales. Nocardia and rapidly growing atypical bacteria can cause wound infections, but the wounds would have a different appearance, with more drainage and no black necrosis. Thus, trimethoprim‐sulfamethoxazole and clarithromycin are not the best choices for addition to the therapy. Also, these infections could be diagnosed rapidly with Gram or acid‐fast stains, making empiric therapy unnecessary. Daptomycin would cover vancomycin‐resistant Enterococcus, but this infection would also be associated with more ftlineacute changes in the wound and increased drainage. 21
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Aspergillosis
Study Table:Pulmonary Aspergillosis Syndromes
Condition
Characteristics
Allergic bronchopulmonary
aspergillosis
Usually occurs in the setting of asthma or CF. Other findings are a positive skin test, elevated IgE, and eosinophilia. Presents as difficult‐to‐control asthma and recurrent pulmonary infiltrates.
Aspergilloma (fungus ball)
Occurs in preexisting pulmonary cavities or cysts, or in areas of devitalized lung. Symptoms are cough, hemoptysis, dyspnea, weight loss, fever, and chest pain.
Invasive sinopulmonary
aspergillosis
Occurs in immunocompromised hosts. CT scan may show the “halo sign”, a target lesion with a necrotic center and surrounding ground‐glass attenuation (hemorrhage).
Aspergillosis • Neutropenic oncology patients and organ transplant recipients are at increased risk for developing Aspergillus infections. An effective noninvasive diagnostic test is not available. Blood cultures are rarely positive. The gold standard diagnostic test for Aspergillus infection is obtaining cultures from deep‐body specimens. The serum galactomannan
enzyme assay can support the diagnosis in the right clinical setting, and it can be followed serially to assess response to therapy.
• Therapy
• Voriconazole is a reasonable first‐line treatment in patients with documented or suspected invasive aspergillosis. Treat allergic bronchopulmonary aspergillosis with oral corticosteroids.
Endemic mycosis Infection
Geographic Distribution
What to Look For
Symptom onset 4‐6 weeks after exposure
Midwestern, southeastern, and Blastomycosis
Consider in patients with primary skin lesion south central United States (Blastomyces dermatitidis) (Mississippi, Missouri, and Ohio river or concurrent pulmonary and skin findings
Consider in patients with acute pneumonia or valleys)
subacute lung disease (e.g., TB, malignancy)
Coccidiomycosis
(Coccidioidesspecies)
Southern Arizona, south central California, southwestern New Mexico, west Texas
Symptom onset 1‐3 weeks after exposure
Consider in patients with pulmonary symptoms and erythema nodosum or erythema multiforme
Consider in patients with pulmonary symptoms and prolonged constitutional symptoms (fever, fatigue)
Histoplasmosis
(Histoplasma capsulatum)
Midwestern states in the Ohio and Mississippi valley regions
Symptom onset 2‐3 weeks after exposure
Consider in patients with complex pulmonary disease (nodular, cavitary, lymphadenopathy)
Consider patients being evaluated for sarcoidosis, TB, or malignancy
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Q 23
• A 32‐year‐old woman who is in the 27th week of a supervised pregnancy with her third child requests information on vaccination for herself. She has two children, aged 2 and 4, who have received appropriate childhood vaccinations from their pediatrician. As a child, the patient was immunized against polio, measles, mumps, rubella, and varicella. She was given combined tetanus‐diphtheria‐acellular pertussis (Tdap) vaccine during her last pregnancy. She was immunized against HBV while in high school, but she has no antibody titer. She is CMV antibody negative. The patient is married and monogamous. She practices no high‐risk behavior.
• In addition to influenza vaccine, which of the following immunizations should this pregnant patient receive?
A. No additional vaccine
B CMV vaccine
C HBV vaccine
D . HPV vaccine
E Tdap vaccine
Ans E • A new recommendation in 2013 by the Advisory Committee on Immunization Practices counsels immunization against pertussis during each pregnancy, preferably between 27 and 36 weeks of gestation, and regardless of prior vaccination status. This vaccination passively immunizes the fetus and the neonate. The incidence of pertussis has been rising in the United States. Postvaccination immunity has been shown to wane over time. In one study, women who had been immunized against pertussis within two years had only low levels of anti‐pertussis antibodies, such that only 40% of infants would be expected to have detectable antibodies at 2 months of age. Infants younger than 3 months are at highest risk for morbidity and mortality from pertussis, and passive immunization does afford protection. There have been no reports to the Vaccine Adverse Event Reporting System of any adverse events associated with two doses of combined tetanus, diphtheria, and acellular pertussis vaccine. Data are limited on more than two doses but do not suggest increased risk. Although hepatitis B vaccine may be given to pregnant women safely, as it is a subunit vaccine, it is optional. It may be that this woman is a nonresponder to the vaccine. Based on her history, she is at low risk for acquisition of hepatitis B virus infection. Although human papillomavirus vaccine (HPV) is not a live virus vaccine, it is specifically not recommended during pregnancy because its safety has not been fully evaluated. HPV vaccine can be given after delivery, during lactation. Although CMV infection acquired during pregnancy can be associated with significant morbidity, there is at present no approved vaccination to prevent it. 24
• You are seeing a 24‐year‐old man who has had a cochlear implant for three years. He also has had well‐controlled insulin‐dependent diabetes mellitus for ten years. A hemoglobin A1C value from two months ago was 5.4% [4.0‐6.1]. Shortly after he was found to have diabetes mellitus, he received the pneumococcal 23‐valent polysaccharide vaccine (PPS23). At age 17, before attending college, he was immunized for meningococcus; combined tetanus, diphtheria, and pertussis (Tdap); measles, mumps, and rubella; and human papillomavirus. Which of the following is the most appropriate immunization strategy for this patient now?
(A) Give a combined Tdap vaccine booster
(B) Give a meningococcal vaccine booster
(C) Give a booster dose of the PPS23 vaccine
(D) Give the 13‐valent pneumococcal conjugate vaccine (PCV13)
(E) No additional immunizations are indicated at this time
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Ans D
• The Advisory Committee on Immunization Practices recently approved the use of the conjugate vaccine for adults 19 and older who are immunocompromised, asplenic, or have a cochlear implant. Specifically, the recommendation states that such patients who have been immunized with the 23‐valent pneumococcal polysaccharide (PPS23) vaccine in the past should get a dose of the 13‐valent pneumococcal conjugate (PCV13) vaccine one or more years later. If they have never been vaccinated to prevent pneumococcal infection, they should be given a dose of the conjugate vaccine followed by a single dose of the polysaccharide vaccine at least eight weeks later. Tetanus, diphtheria, and pertussis (Tdap) vaccination is given only once, and meningococcal vaccine is not indicated for any adult unless there is an increased risk of exposure, such as travel to endemic areas or employment in a microbiology laboratory.
25
• A group of students from a local university traveled to Costa Rica for their spring break. They did not obtain any pre‐travel counseling. One of their parents specifically warned against the dangers of using insect repellents containing diethyltoluamide (DEET). During the trip, the students stayed in a number of low‐budget hostels, drank local water, swam in salt water, and slept on a beach. Other than travelers' diarrhea, no illnesses were reported during the trip. • Approximately one month after returning home, three of the students noted the development of one to four painless, slowly enlarging papular skin lesions. Several of the lesions ulcerated. The three students were examined by local dermatologists and treated with clindamicin, cephalothin, and linezolid without benefit. Superficial cultures were taken from the three students. One culture grew MRSA, one grew a number of skin flora, and one grew methicillin‐susceptible Staphylococcus aureus. All three students were treated with mupirocin. No one had fever or was systemically ill, and all were able to attend classes without difficulty. One of the affected students continued to play on an intercollegiate sports team. • Examples of the skin lesions are shown .No pathergy was noted. Which of the following is the most likely diagnosis of these students' skin lesions?
A) Pyoderma gangrenosum
(B) Mycobacterium ulcerans infection
(C) Leprosy
(D) Sporotrichosis
(E) Leishmania viannia infection
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Ans E
• Although many persons travel to Costa Rica annually, the acquisition of cutaneous leishmaniasis is remarkably rare. These students were ill advised to avoid diethyltoluamide (DEET)‐containing insect repellents because they have been used by millions of individuals, and no studies have shown any significant untoward effects. DEET is the only clinically effective agent available in this country. Illnesses borne by sand flies, mosquitos, and ticks have been associated with significant morbidity and mortality, and measures should be taken to avoid being bitten by these insects. The diagnosis of leishmaniasis requires thoughtful analysis followed by biopsies for histology and PCR. Advice and proper transport media can be obtained from the Centers for Disease Control and Prevention. Mycobacterium ulcerans, the cause of Buruli ulcer, is widely distributed throughout the tropics, but most of the cases are from rural West Africa. An outbreak that simultaneously involves three travelers would be distinctly unusual, as would multiple lesions. Sporotrichosis can also cause cutaneous ulcerations, but no inoculation trauma is described, and, again, an outbreak would not be typical. When pyoderma gangrenosum ulcerates, the ulcer is typically deep with undermined edges. The base is often purulent, and the lesion is painful. Although the lesions of leprosy are often painless (or anesthetic), they very rarely ulcerate. Leprosy has a much longer incubation period and requires prolonged exposure for transmission. Leprosy would not be seen as an outbreak in a group of short‐term travelers.
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• 0‐12 weeks
Ampicillin/3rd generation cephalosporin
• 3 mo to 50 years
3rd generation cephalosporin/vancomycin
• >50 years
Ampicillin/3rd generation cephalosporin/vancomycin
• steroids: recommended now for acute bacterial meningitis to be given prior to or concomitant with antibiotics
Neurology. 2010 Oct 26;75(17):1533‐9. Epub 2010 Sep 29.
Nationwide implementation of adjunctive dexamethasone therapy for pneumococcal meningitis.
Brouwer MC, Heckenberg SG, de Gans J, Spanjaard L, Reitsma JB, van de Beek D.
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» Caused by Treponema pallidum, a spirochete
» Initial presentation:
˃
˃
˃
˃
˃
Painless genital ulcer=chancre
Usually indurated, indolent, and sharply demarcated
Appears after an average of 3 weeks of infection
Painless regional lymphadenopathy is common
Heals spontaneously within 3‐6 weeks » Diagnosis:
˃ Direct exam=darkfield examination
˃ Non‐treponemal tests: RPR or VDRL (measure IgG/IgM to cardiolipin/lipoidal material released from damaged cells)
˃ Treponemal tests: FTA or MHATP (measure antibodies to specific treponemal components)
» Treatment
˃ Early (primary, secondary or early latent)
+ Benzathine penicillin G, 2.4 MU X 1 dose
+ Doxycycline 100 mg BID X 2 weeks
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








A 35‐year‐old man presented with a rash followed by malaise and fever. The rash started on his face and spread to the trunk, extremities and genitalia over 2 days. He has no underlying illnesses.
He does not know which childhood immunizations he had. No pet, no sick contacts, no travel, no promiscuous sexual activity.
Exam:
Temperature 37.8°C Pulse 90 BP122/80 He is iIll appearing with injected conjunctiva, oral and genital ulcers, and a vesicluar rash mainly on face, back and chest (see images).
WBC is 7.5 (normal diff), routine blood work normal.
What is the most likely diagnosis?

A) Measles

B) Disseminated HSV

C) Chicken Pox (primary VZV)

D) Smallpox

E) Pemphigus vulgaris
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This is chicken Pox (Varicella):  Characteristic vesicles on erythematous base at DIFFERENT stages  Constitutional symptoms start AFTER rash (or mild before rash)  Lesions begin in more central locations  Can have mucous membranes (oral and genital ulcers) involved.  Measles:
 Fever and upper respiratory prodrome before rash  Rash starts 2‐3 days after onset of fever on head and progresses down, but much different appearance (no vesicles, see image below) and lasts for a week; pruritic  Koplik spots on buccal mucosa on third or fourth day of illness  Extremely rare in this country even if not immunized, but he probably was immunized in order to enter school.  Rubella
 Mild disease that only last 2‐3 days  Conjunctivitis and runny nose plus arthralgias, especially in younger women  Occipital lymphadeopathy
 Rash starts on face and spreads to trunk and is fine vs. blotchy measles rash  Small Pox:
 Lesions more centrifugal, (see image below)  Vesicles/pustules at SAME stage  Febrile prodrome BEFORE rash  Not possible in the current era unless bioterrorism attack suspected 
 A healthcare worker sustains a deep needle stick with a hollow bore needle that was just used to drawn blood from a patient with hepatitis B (HBsAg positive) who was being assessed for hepatitis B treatment, but who had not yet started therapy.
 The healthcare worker previously was immunized for hepatitis B seven years ago and was documented immediately after that immunization series to have an adequate antibody response (antibody level >10 units/uL)

Which of the following would be the best option for this exposed worker?
 A) HBIG
 B) Lamivudine plus entecavir for at least 4 weeks
 C) HBIG and a minimum of four week course of Lamivudine and Entecavir
 D) HBIG and Lamivudine and Entecavir plus an HBV vaccine booster
 E) No therapeutic intervention
 This patient was immunized to hepatitis B, as all healthcare workers should be, and was documented to have an adequate serologic response. Some experts would provide a booster dose of HBV vaccine (this alone was not an option in this question), but neither HBIG nor chemotherapy for HBV is indicated for this patient.
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Selected bacteria and their associations
• Strep bovis bacteremia: colon CA
• Strep viridans bacteremia: endocarditis
• CNS, Staph aureus bacteremia: line infections
• Staph aureus in urine and/or blood: endocarditis
QUESTION 31