Super cool HIV interactive graphic

The New England Journal published the studies of raltegravir's use/efficacy for patients with an optimized background regimen (OBR) recently, and it turns out they also had an online-only interactive graphic that would be great for teaching students and residents visiting on the service. It's online at:

http://content.nejm.org/content/vol359/issue4/images/data/339/DC2/AIDS_Interactive.shtml

Enjoy!

– Christopher Hurt, MD

Sexual Assaults and PEP

There is a protocol that can be obtained from Lynda Bell in clinic regarding the care of survivors of sexual assaults. We will sometimes be called to weigh in on HIV PEP alone, as they have a protocol they follow for everything else. However, if you are ever called about what should be done, particularly if a SANE nurse is not available, here are some basics from the protocol.

Baseline laboratory tests should include:

• HIV Antibody testing
• CBC with differential
• LFTs
• BUN/Creatinine
• STD Screen (gonorrhea, chlamydia, syphilis)
• Hepatitis B serology
• Hepatitis C serology
• Pregnancy test

Prophylaxis against the most frequently diagnosed STDs among sexually assaulted women should be administered:

• Ceftriaxone 125mg IM in a single dose [Gonorrhea]
• Metronidazole 2gms orally in a single dose [BV, Trichomoniasis]
• Azithromycin 1gm orally in a single dose OR Doxycycline 100mg orally twice daily for seven days [Chlamydia]

HIV post-exposure prophylaxis is offered within 72 hours of the assault. If the perpetrator's HIV medical history is unknown, the two preferred regimens are:

• NNRTI-based: Efavirenz plus (Lamivudine or Emtricitabine) plus (Zidovudine or Tenofovir)...usually as Sustiva plus Combivir, or Sustiva plus Truvada.
• PI-based: Lopinavir/Ritonavir (Kaletra), plus Zidovudine or Tenofovir...usually as Kaletra plus Combivir, or Kaletra plus Truvada.

I've been advised typically to use the PI-based regimen unless there is another reason they should be avoided. Keep in mind that if the source patient (in the case of needlesticks) is one of OUR HIV clinic patients, we have access to their genotype and med history, and can formulate an appropriate PEP for the victim based on this information (i.e. you wouldn't want to start someone on PEP that their virus would be resistant to).

All sexual assault cases should follow up with a mid-level provider in the ID Clinic, regardless of whether or not they accept PEP. We usually just send a phone message to Lynda Bell with the patient's general information, and she contacts them to set up a follow up within 48 hours or so.

Risk Assessment

Sometimes, you are asked to comment on the risk, given different exposures (assault, blood splashes in the eye, needlestick, etc.). The risk for HIV acquisition per various acts can be found in the MMWR, January 21, 2005). It is also estimated in the Sanford Guide for the treatment of HIV.

Vaccinations in PEP

Hepatitis B: Patients who are unvaccinated prior to the assault should receive the initial Hep B vaccine, and follow up to complete the series. Unless the offender is known to have Acute Hep B, HBIG is not required. Remember, all patients should have serologies drawn.

Tetanus: If the patient has skin abrasions or other wounds and immunization status is greater than 5 years, give Tetanus Toxoid 0.5ml IM. If the patient has never been immunized, also give Hyper-Tetanus 250mcg IM.

Yvonne Carter, MD

Review of PPDs

We have a lot to learn regarding TB, but regarding the targeted testing for latent tuberculosis infection, here is a VERY QUICK review of what constitues a positive PPD:

>0 mm is considered a positive reaction if the patient:

• Is HIV-positive or immunocompromised AND are recent contacts to known or suspected infectious TB disease, regardless of previous treatment of LTBI
• Is HIV-positive with fibrotic changes on CXR consistent with prior TB who have received inadequate or no treatment for TB disease
• Is a child <5>

>5 mm is considered a positive reaction if the patient:

• Is HIV-positive
• Is a contact to known or suspected infectious TB case identified within the last two years
• Has fibrotic changes on CXR consistent with prior TB and have received inadequate or no treatment for TB disease
• Is Immunocompromised (receiving >15mg per day of Prednisone for one month, other immunosuppressive drugs, organ transplant recipients, persons taking TNF inhibitors)

>10 mm is considered a positive reaction if the patient:

• Is foreign-born from Asia, Africa, Carribean, Latin America, Mexico, South America, Pacific Islands, or Eastern Europe)
• Has converted their TST within two years
• Has a medical condition placing them at high-risk for TB Disease (DM, CRI, Chronic malabsorption syndrome, Leukemias and Lymphomas, Cancer of the head and neck, Silicosis, Weight loss of >10% ideal body weight, gastrectomy or intestinal bypass)
• Is an injection drug or crack cocaine user
• Is a child <4>
• Works in a mycobacterial lab

*Also, this cutoff is used per the clinicians judgement for: residents of long-term care facilities and homeless shelters, are inmates in the DOC, OR are employees in prisons/jails, long-term care facilities, hospitals/health care facilities, adult day-care centers for HIV patients, homeless shelters).

>15 mm is considered a positive reaction if the patient:

• Has NO risk factors for TB

Hope this helps!

Yvonne Carter, MD

HIV, Syphilis, and When to LP

Syphilis is a significantly prevalent STD in North Carolina, particularly in the setting of co-infection with HIV. Screening for syphilis is reviewed in the Syphilis Screening section of the blog. But, a common question that must be addressed in this circumstance is:

When is it necessary to perform an LP in to rule out Neurosyphilis in the HIV-positive patient?

The answer has many answers, but the commonly accepted answer is as follows: "All neurologically asymptomatic HIV-infected patients whose serum RPR titer is greater than or equal to 1:32 should undergo lumbar puncture regardless of syphilis stage." And, of course, any symptomatic HIV-patient with a history of syphilis should undergo LP to rule out Neurosyphilis.

This recommendation is taken from two main studies:

• Marra, et al. J Infect Dis 2004; 189: 369 - 376.
• Libois, et al. Sex Transm Dis 2006. HIV and syphilis: When to perform a lumbar puncture.

Yvonne Carter, MD

MRSA, MRSA me, Staph ain't what it used to be...

Apologies for the title, I couldn't help myself.  :)

ORSA comes up a lot, specifically how to decolonize patients with community-acquired ORSA (CA-ORSA). The UNC hospital epi people put together a brochure, which is sometimes hard to locate. I found this PDF online, from Kaiser Permanente out in California, which outlines I think what's pretty standard for us around here:

http://www.kplearning.com/10_national_site/uploads/B1S3.pdf

Johns Hopkins used to publish this nice periodic newsletter on HIV issues, but they've discontinued it due to time and budget constraints. Nevertheless, there was a nice article in the September 2004 edition that addressed CA-ORSA:

http://www.hopkins-hivguide.org/images/publications/nl_04_sept.pdf

The only caveat I'd put on this is, please know that the conventional dosing of TMP/SMX (Bactrim™, Septra™) at one DS tablet twice a day (as in the Hopkins thing) is now considered insufficient for ORSA treatment (at least around here, anyway). You need TWO DS tabs twice daily, and make sure you adjust for renal function, if reduced.

In general, we use doxycycline as our second-line agent, followed by clindamycin. Our micro lab will report clindamycin susceptibility separate from erythromycin – but outside labs may not be as reliable. Remember that CA-ORSA may have inducible resistance to the lincosamides (of which clinda is one) that won't show up in microdilution susceptibility testing used in outside hospitals and labs. You can't detect this is unless a "D-test" is performed, with both an e-mycin (15 µg)  and a clinda (2 µg) disk dropped onto the plate:

If the bug has inducible resistance, there'll be a flattening of the zone of inhibition between the two disks, suggesting that the bugs closer to the e-mycin disk have switched on their inducible resistance genes and are now laughing at the silliness of you attempting to use clindamycin to kill them.

Editorial note: The acronym "MRSA," for methicillin-resistant Staphylococcus aureus, is a humongo misnomer, since we don't use methicillin for resistance testing, and haven't in many years. Oxacillin is used on the plates, not methicillin – so you may hear it referred to more often in the micro lab as ORSA, and more often in the community as MRSA. If you're an ID purist, go with ORSA and look smart when someone asks what the hell it is that you're saying. (Or look like a big know-it-all dork. :)   )

 

– Christopher Hurt

Osteomyelitis...

... is the bane of the consult service existence. Well, along with the entire Family Medicine service, most of surgery, the impossibly perky OB-Gyn residents... but I digress. But osteo pretty much sucks. The question comes up pretty often, how do we best diagnose osteomyelitis, especially in the diabetic foot patients? This question was answered I think pretty comprehensively in the August 15, 2008 issue of Clinical Infectious Diseases. You can read it here, through UNC:

http://www.journals.uchicago.edu.libproxy.lib.unc.edu/doi/full/10.1086/590011

and the little editorial blurb that followed it is here:

http://www.journals.uchicago.edu.libproxy.lib.unc.edu/doi/full/10.1086/590012

– Christopher Hurt

Malaria prevention

Malaria stuff we get hit with pretty regularly, especially by student health in the summertime when lots of undergrads and grad students go globe-trotting. The New England Journal published a pretty helpful article in August 2008, on malaria prevention in short-term travelers. You can access it through UNC at:

http://content.nejm.org.libproxy.lib.unc.edu/cgi/content/full/359/6/603

(Plus it has a really sweet picture of the life cycle of malaria, along with where the drugs work.)

– Christopher Hurt

Serologic Testing/Screening for Syphilis

When on consults, we are commonly called to interpret the meaning of serologic testing for syphilis (and other diseases like RMSF and Lyme as well). When evaluating the results of testing, a clinical history is imperative to interpretation. Does the patient have a history of syphilis, to their knowledge? Treated or untreated? If treated, how were they treated?

The following is taken directly from PPID Online (Mandell's), but explains testing well:

Confusion surrounds interpretation of the serologic tests for syphilis, principally because two different types of antibodies are measured: the nonspecific nontreponemal reaginic antibody and the specific anti-treponemal antibody. The test for the former is inexpensive, rapid, and convenient for screening large numbers of sera (e.g., donated blood) and as an indication of disease activity. Specific antibody tests establish the high likelihood of a treponemal infection, either currently or at some time in the past. To establish a diagnosis of syphilis, the two types of serologic tests are most often used together, although attempts to improve the single tests are ongoing. It should be emphasized that serologic test results for syphilis on rare occasions may be negative in active cases, especially in older patients.

Non-Treponemal Tests

A fourfold change in titer using the same test method, either VDRL or RPR, is necessary to demonstrate a clinically significant difference, preferably being performed in the same laboratory at the same time. Nontreponemal antibody tests vary during the course of untreated disease. They reach their highest prevalence and titer during the secondary and early latent stages and decline thereafter, usually to less than 1:4. Over time, at least 25% of untreated persons become VDRL or RPR negative, even without treatment. A persistently high-titered RPR or VDRL result is more common in HIV-infected persons because of the polyclonal antibody stimulation, a manifestation of immune dysfunction often seen in these patients, especially in early HIV disease.

The quantitative VDRL/RPR test should become nonreactive 1 year after successful therapy in primary syphilis and 2 years after successful therapy in secondary syphilis. Most patients with late syphilis should be nonreactive by the fifth year after treatment. The time required for the test to become negative correlates with the interval between contact and institution of therapy and with the severity of illness, especially with the type of skin lesions manifested in the secondary stage (i.e., a patient with a macular rash reverts to a negative titer sooner than does a patient with a papular rash). Therefore, a positive VRDL or RPR response after 1 year in a patient treated for primary syphilis or after 2 years in a patient treated for secondary syphilis suggests persistent infection, reinfection, or a biologically false-positive reaction. A patient with adequately treated late syphilis should have a negative response after 5 years. As with all quantitative serologic tests, only a fourfold or greater change in titer is meaningful.

Specific Treponemal Tests

These tests measure antibodies against specific T. pallidum antigens. The principal specific anti-treponemal antibody tests performed today are the FTA-abs and T. pallidum agglutination tests (TPHA and MHA-TP). These tests would be relatively expensive as screening tests, and if they were applied to a low-risk population, the number of false-positive reactions would increase proportionately. Therefore, their principal use is to verify a positive nontreponemal reaginic test result. Once positive, the patient usually remains positive for life. However, reversion to a nonreactive status may occur in up to 10% of patients, especially in those who are treated early.

When the diagnosis of syphilis is being seriously considered in an individual patient, the TPHA, MHA-TP, or FTA-abs test should be done. Once these have become positive and the diagnosis is established, the usefulness of these tests is limited because they can remain positive for life. A nontreponemal antibody test is very helpful for monitoring the efficacy of therapy. The failure to fall more than fourfold or become negative suggests a persistent infection, reinfection, or a false-positive test.

False Positive Testing

The likelihood of a biological false-positive (BFP) reaction depends on the population being studied. Acute or transient false-positive nontreponemal reaginic test reactions may occur whenever there is a strong immunologic stimulus (e.g., acute bacterial or viral infection, vaccination, intravenous drug abuse, HIV infection). Positive reactions persisting for months occur in the presence of continued parenteral drug abuse; with autoimmune or connective tissue diseases, especially systemic lupus erythematosus; with aging (in up to 10% of those older than 70 years of age); in hypergammaglobulinemic states; and in HIV coinfection. A false-positive nontreponemal reaginic test in this setting tends to be associated with other serum factors frequently associated with autoimmune diseases, such as antinuclear, antithyroid, or antimitochondrial antibodies, rheumatoid factor, and cryoglobulins.

A false-positive nontreponemal reaginic test can usually be verified (and syphilis excluded) by obtaining a negative specific treponemal antibody test (FTA-abs, TPHA, MHA-TP). However, at times the same illnesses that produce a false-positive nontreponemal reaginic test (e.g., systemic lupus erythematosus) also result in a positive or borderline-positive FTA-abs test reaction. Also, the FTA-abs may be positive when the VDRL is negative and vice versa. This false reaction can often be suggested by noting a beaded pattern of immunofluorescence on the treponemes, but the best definitive way to make the distinction is to obtain the functional but rarely available TPI test, PCR or immunoblotting using specific T. pallidum antigens such as 17-kDa, and so forth. Other spirochetal illnesses, such as relapsing fever (Borrelia spp.), yaws, bejel, pinta, leptospirosis, or rat-bite fever (Spirillum minor), also yield positive nontreponemal and treponemal tests. Infection with Borrelia burgdorferi (Lyme disease) results in a positive FTA-abs test but does not cause a positive nontreponemal reaginic reaction (VDRL or RPR).

Yvonne Carter, MD
http://www.ppidonline.com/content/default.cfm

Working with the Health Department regarding Tuberculosis Management

North Carolina Health Departments are a vital resource for TB evaluation and management. In most cases, Tuberculosis evaluation can be done as an outpatient, and does not require inpatient admission and evaluation, or ID clinic follow up. Each Health Department houses a TB Clinic, whose responsibilities include:

• providing case management to all active cases of TB,


• evaluating all persons suspected of having TB,


• evaluating all contacts of active and suspect cases within the county, and


• providing TB screening to predetermined high-risk individuals, including recent immigrants.

Evaluation, treatment, and care is provided to each patient free of charge. It is important to note that patients can be referred to the Health Department during any part of the workup for TB, from suspicion through post-diagnosis care. If a patient is hospitalized at UNC, and is on isolation for suspicion of TB, and is otherwise ready for discharge, they may be discharged with a mask to follow up with the Health Department. The Health Department, however, MUST be notified of the patient's discharge, and set up an appointment for the patient to be seen by them. There, they can complete sputum collection, PPD placement and reading, and contact investigation. Again, the pt must present to the Health Department with a mask if TB is suspected. If a patient is suspected of having Tuberculosis, but refuses follow-up with the Health Department, that patient's workup should be done as an inpatient.

If a patient has a positive sputum AFB smear, and treatment is initiated, you will need to give the patient enough doses to last them until they can be seen at the Health Department (the next day if during the week, and on Monday if during the weekend). The Health Department will treat TB only, not infections caused by nontuberculous mycobacterium.

A directory of health departments for each county can be found at: http://www.ncalhd.org/county.htm.

Yvonne Carter, MD

Communicable Disease Reporting

Communicable diseases are reported first to the County Health Departments who go on to report to the State. Reporting through the county Health Department is necessary because they typically conduct thorough contact investigations. Traditionally, communicable diseases have been reported through the use of the "North Carolina Communicable Disease Report Card." However, the use of these cards is being phased out by the State, and they are changing to a fully electronic reporting system. The North Carolina Communicable Disease website is: http://www.epi.state.nc.us/epi/gcdc.html, and here, PDF versions of reporting are available for a variety of communicable diseases.

It is expected that laboratories will be responsible for reporting communicable diseases, but the new online forms require a fair amount of clinical background, and therefore, we should be prepared to assist our lab if further information is needed.

The current CDC list of Nationally Notifiable Infectious Diseases can be found at this website:
http://www.cdc.gov/ncphi/disss/nndss/PHS/infdis2008.htm.


Arlene Sena-Soberano, MD, MPH, is the Medical Director of the Durham County Health Department, and is a key connection between UNC and the Health Department. She can be contacted with further questions regarding communicable disease reporting, at email address arlene_soberano@med.unc.edu.


Yvonne Carter, MD

Viral Hepatitis Screening

Testing or screening for Hepatitis will depend on the clinical situation: i.e. whether the patient is asymptomatic, has a history of exposure, has high risk behaviors, or is clinically symptomatic (elevated transaminases, jaundice, nausea, vomiting, etc.). Generally, we'd recommend screening in any symptomatic patient, all HIV patients at the time of diagnosis, and IV drug users. Routine screening (hepatitis panel) should include screening for:

• Hepatitis A, with total antibody to HAV (anti-HAV Ab)* or IgM antibody to HAV (IgM anti-HAV).
• Hepatitis B, with Hepatitis B surface antigen (HBsAg) and IgM antibody to hepatitis B core antigen (IgM anti-HBc).
• Hepatitis C, with Antibody to HCV (anti-HCV).

Special Populations

• Routine screening of pregnant women for HBsAg is done to identify infants of infected women who require post-exposure prophylaxis.
• High risk populations for chronic HBV infection (e.g., STD and drug treatment patients, inmates of correctional facilities, immigrants from countries with a HBsAg prevalence >2%) might benefit from routine HBsAg testing, but the feasibility and cost effectiveness of such testing in various clinical settings has not been determined.
• Recommendations have been developed for routine anti-HCV testing for persons at high risk of HCV infection (i.e., persons who have ever injected illegal drugs, persons who received a blood transfusion or organ transplant before July 1992, persons ever on chronic hemodialysis, persons who received clotting factor concentrates made before 1987, persons with abnormal liver enzyme levels).

Confirmatory Testing

• The presence of other serologic markers of HBV infection (i.e. total anti-HBc or IgM anti-HBc) can be used to evaluate the likelihood that an HBsAg positive test result is a true positive but isolated HBsAg positive test results should be verified by a confirmatory assay (e.g. neutralization assay).
• Anti-HCV positive results by enzyme immunoassay (EIA) should be verified by a supplemental antibody assay (e.g., RIBA), which is available through McLendon labs. Detection of HCV RNA by RT-PCR verifies HCV infection, but the absence of detectable RNA in a single serum specimen does not exclude the possibility of HCV infection.

Yvonne Carter, MD

Vancomycin

Our patients are frequently on Vancomycin, due to the increasing incidence of ORSA in both hospital-acquired infections, and community-acquired infections. ORSA can cause a variety of infections, and we commonly follow patients with ORSA pneumonia, cellulitis, deep soft tissue infections, abscesses, osteomyelitis, bacteremia and endocarditis. Vancomycin does also cover other gram-positives, but is the treatment of choice for ORSA infections. It is the treatment of choice in PCN-allergic patients with gram positive infections. There are several important things to remember when treating a patient with Vancomycin:

1. Weight and renal function (measured by GFR or creatinine clearance). Both will influence the therapeutic dosing of Vancomycin. Generally, Vancomycin is dosed 15-20 mg/kg, and given q12h hours in patients with normal renal function.

2. Vancomycin is not absorbed systemically when given orally. Therefore, po Vancomycin is only approved as second-line treatment of C. difficile colitis. Otherwise, it should ALWAYS be given intravenously.

3. Weekly labs. When on Vancomycin, weekly labwork should be checked and should include: CBC with differential, BUN and creatinine, and Vancomycin trough.

4. Goal troughs. Vancomycin is monitored via the collection of troughs, which should be drawn ~30 minutes prior to the next scheduled dose. In general, peak testing is unnecessary. The goal trough will depend on the site of infection (keeping in mind that these goals have been extrapolated from other data, and have yet to be verified in clinical studies):

1. Goal trough of 15-20 mcg/ml is reserved for Pneumonia, Endocarditis, Meningitis, and Osteomyelitis.


2. Goal trough of 10-15 mcg/ml is used for skin and soft tissue infections and Bacteremia.

5. Adverse Reactions.

1. "Red Man Syndrome." A systemic response to the infusion, that includes flushing and sweating. Is not dangerous, and is not an allergy. It can usually be remedied by slowing the infusion rate, and/or diluting the Vancomycin in a larger volume of solute.


2. Ototoxicity. Generally not reversible, and occurs at high levels.


3. Renal failure. Uncommon, except when Vancomycin is given concomitantly with other nephrotoxic agents. If a patient develops ARF while on Vancomycin, you can generally continue Vancomycin, making dose adjustments, while the cause of the ARF is being worked up.

***In terms of when we follow Vancomycin levels, we should follow Vancomycin levels on patients on which we recommended the use of IV Vancomycin when seen as an inpatient AND will follow up with you in ID Clinic. In cases where we do not plan to see the patient in follow up, the team should make arrangements for that patient's outpatient provider to follow labwork. You may volunteer to follow labwork on these patients if they have no provider to do so. BUT, you should NEVER follow Vancomycin levels or labs on patients whom you have not seen. We have been called to follow labs on patients being discharged from various services who are going home or to a SNIF on Vancomycin. The answer to this request should be a firm NO. It becomes a legal liability when following labwork on a patient you don't know and have never seen, and in whom you did not recommend Vancomycin in the first place. What if they develop an adverse drug reaction??? Who is responsible? On paper, you would be, as the ordering physician. So, keep that in mind. Most services have no staff in place assigned to follow labwork on patients on IV antibiotics, and remember, NEITHER DO WE. It is our responsibility as fellows to follow it on our patients only. We should not volunteer to do it as a service for the entire hospital. Just imagine how many labs we would be following if we monitored labs on every patient discharged on Vancomycin from UNC?!?! Please make requesting services aware of this.***

Yvonne Carter, MD