Post-Exposure Prophylaxis

Emergency medicine is dangerous work. Here’s a rundown of some of the greatest infection threats and their appropriate prophylactic agents 

As emergency physicians we are exposed to patients with a host of different infections, and sometimes are required to take post-exposure prophylaxis to prevent infection. Here is a look at some of the risks we encounter and the more common testing and post-exposure prophylaxis (PEP) agents you might need to know, either for your own practice as a healthcare provider (HCP)2, or for board exams.

H.I.V.
Risk: The risk of seroconversion following a needlestick with blood from an HIV-infected patient depends on several factors. However, on average, if no post-exposure prophylaxis is given, the risk is about 0.33% after a needlestick injury. Infection from mucosal exposure has been reported, but rates are very low, around 0.09%3. A CDC study specifically identified four statistically significant risk factors4:

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• A deep injury (OR 15)
• Injury with a needle or device that had visible blood contamination (OR 6.2)
• Injury with a needle that had been placed in the source patient’s artery or vein (OR 4.3)
• Death of the source patient from AIDS within 2 months (OR 5.6), which is thought to be due to the higher viral load.

In the CDC case control study, HCPs who seroconverted were less likely to have received post-exposure zidovudein (OR 0.19)3.

Testing: The source patient should undergo rapid testing for HIV, though PEP should not be delayed if the patient refuses testing. If the source patient tests negative for HIV, the PEP can be discontinued. The HCP should be tested for HIV at baseline, and at 6 weeks, 3 months, and 6 months after the exposure to assess for seroconversion.

Prophylaxis: The sooner PEP is started, the better. The CDC recommends beginning treatment within 36 hours of the exposure, but it can be initiated up to 72 hours afterwards4. Common regimens involve treatment for 28 days with one of the following combinations2:

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• Tenofovir-emtricitabine (300/200 mg daily) and raltgravir (400mg BID)
• Tenofovir-emtricitabine (300/200 mg daily) and atazanavir (300mg daily) and ritonavir (100mg daily)
• Tenofovir-emtricitabine (300mg/200mg daily) and darunavir (800mg daily) and ritonavir (100mg daily)

Unfortunately, HIV PEP treatments are not without side effects. About half of patients experience some side effects, and up to one third discontinue treatment because of them2. Common side effects include nausea, vomiting, diarrhea, fatigue, and headaches. Less common side effects include hepatitis, fevers, hyperglycemia, pancytopenia, and rashes2. HCPs receiving PEP should be monitored with a CBC, liver function tests, and creatinine, at 0, 2, and 4 weeks after starting PEP. Those taking protease inhibitors (atazanavir, darunavir, and ritonavir) should also be monitored for hyperglycemia. Tenofovir and emtricitabine carry black box warnings for lactic acidosis and severe heptaomegaly, as well as exacerbation of hepatitis in HBV-infected individuals on discontinuation of the treatment.

HEPATITIS C (HCV)
Risk: As with HIV, the risk of exposure after a percutaneous injury depends on the depth of injury and the degree of contamination. However, on average the risk of HCV seroconversion is approximately 1.8% (0-7%) after a needlestick exposure with an HCV-positive source5.

Testing: After a potential exposure, the source should be tested for anti-HCV antibodies and for HCV RNA level. If the anti-HCV is negative, or if it is positive but the HCV RNA is undetectable, no further testing is needed. If the HCV RNA level is positive, then the HCP should be tested for baseline anti-HCV antibodies and HCV RNA level.

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Prophylaxis: Unfortunately there are no currently available, effective, post-exposure prophylaxis medications for HCV exposure.

HEPATITIS B (HBV)
Risk: The risk of transmission after a percutaneous exposure with HBV is much higher than for HIV or HCV, and depends on the source’s HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) status. The risk of infection is on the order of 22-37% if the source is positive for only one of the antigens. The risk of developing clinical hepatitis is only 1-6% if the source is HBsAg-positive and HBeAg-negative. The risk of developing HBV infection is as high as 37-62% if the source is positive for both HBsAg and HBeAg, and the risk of developing clinical hepatitis in this case is 22-31%5.

Testing: The need for post-exposure treatment for HBV exposures depends on the vaccination status of the provider and whether the source tests positive for HBV surface antigen (HBsAg). The source patient should be tested for HBsAg. If the HCP has completed the HBV vaccine series, their anti-HBs titer should be measured if it is not already known. Providers who have not received or completed the HBV vaccination series, or who are vaccine non responders (anti-HBs titier <10mIU/mL) should receive post-exposure prophylaxis if the source patient is HBsAg-positive, or if the source cannot be tested.

Prophylaxis: The HCP should receive Hepatitis B Immune Globulin (HBIG) as well as the HepB vaccine. These can be given at the same time, but should be at different sites. The HCP should then complete the rest of the HBV vaccination series, and immunity should be confirmed six months after the HBIG was received. The HBIG should ideally be given within 24 hours of exposure, but can be given up to 7 days afterward    5. Six months after exposure, HCPs who were not previously immune should be tested for transmission with anti-HBc antibody and HBsAg levels.

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BORDETELLA PERTUSSIS
Risk: HCPs who have close exposure to a patient with confirmed pertussis are at risk for contracting it. Close exposure is defined as being within 3 feet of a symptomatic patient, or coming in contact with their respiratory secretions.

Testing: For patients with symptoms concerning for pertussis, such as unexplained cough, post-tussive emesis, and post-tussive “whooping” inspiratory sound, during the first 4 weeks, both a culture and a PCR should be sent. If either is positive, the patient should be considered positive. After four weeks of symptoms, serology should be used to confirm the diagnosis6.

Prophylaxis: Treatment after exposure to pertussis is with a course of azithromycin PO, 500mg on day one, followed by 250mg daily for four days. In macrolide-allergic individuals, bactrim can be used as an alternative7. The CDC states that post-exposure prophylaxis given after contact with an infected individual who is within 21 days of symptom onset can help prevent symptomatic infection8.

MENINGOCOCCEMIA
Risk: The risk of infection with N. meningitides depends on the degree of exposure to respiratory droplets from an infected patient. HCPs can reduce their risk of infection by implementing droplet precautions right away for any potentially infected source patient. In general, chemoprophylaxis is recommended for ‘close’ contacts, that is, those who were in contact with respiratory secretions.

Testing: The source patient should be tested with blood cultures for meningococcemia, and CSF cultures for meningococcal meningitis if possible. In cases of very high suspicion, the HCP may opt to take PEP before cultures turn positive or when cultures cannot be sent because the patient expired. PEP should be taken within 24 hours of the exposure if possible.

Prophylaxis: PEP for HCPs can consist of any of the following three regimens [9]:

• Rifampin 600mg PO BID for two days – not recommended in pregnant women
• Ciprofloxacin 500mg PO single dose – not recommended in pregnant or breastfeeding women, or in cases of outbreaks of ciprofloxacin-resistant N. meningitides.
• Ceftriaxone 250mg IM single dose – safe in pregnancy.

ANTHRAX
Risk: Statistically speaking, you are more likely to encounter the need for anthrax PEP on a board exam than in your practice. However, the situation could arise clinically in the case of a bioterrorism event with inhalational exposure to B. anthracis. Exposed individuals face a long course of antibiotics.

Prophylaxis: Exposed individuals should receive three doses of the anthrax vaccine subcutaneously at 0, 2, and 4 weeks. In addition, they should receive a course of treatment for 60 days with one of the following agents [10]:

• Ciprofloxacin 500mg BID (this is also the first line agent for pregnant and lactating women)
• Doxycycline 100mg BID
• Amoxicillin 1g Q8hrs or Penicillin VK 500mg Q6hrs can be used if the strain is known to be penicillin-sensitive

REFERENCES
1. Henderson DK. Management of needlestick injuries: A house officer who has a needlestick. JAMA. 2012;307(1):75-84.
2. Bartlett JG, Weber DJ. Management of healthcare personnel exposed to HIV. uptodate.com. Updated 2012. Accessed 01/09, 2015.
3. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. centers for disease control and prevention needlestick surveillance group. N Engl J Med. 1997;337(21):1485-1490.
4. Center for Disease Control. PEP 101. HIV/AIDS Web site. http://www.cdc.gov/hiv/basics/pep.html. Updated 2014. Accessed 01/09, 2015.
5. Weber DJ, Rutala WA, Eron J. Prevention of hepatitis B virus and hepatitis C virus infection among healthcare providers. uptodate.com. Updated 2014. Accessed 01/09, 2015.
6. Cornia P, Lipsky BA. Clinical manifestations and diagnosis of bordetella pertussis infections in adolescents and adults. UptoDate Web site. UptoDate.com. Updated 2014. Accessed 01/21, 2015.
7. Cornia P, Lipsky BA. Treatment and prevention of bordetella pertussis infection in adolescents and adults. UptoDate Web site. uptodate.com. Updated 2014. Accessed 01/21, 2015.
8. Centers for Disease Control and Prevention. Pertussis (whooping cough): Postexposure antimicrobial prophylaxis. http://www.cdc.gov/pertussis/outbreaks/pep.html. Accessed 01/21, 2015.
9. Apicella M. Treatment and prevention of meningococcal infection. uptodate.com. Updated 2013. Accessed 01/09, 2015.
10. Wilson KH. Prevention of anthrax. uptodate.com. Updated 2014. Accessed 01/09, 2015.