MOFFITT HOLIDAY PEARLS 12/23/16: PCP Treatment and CNS Antibiotic Penetration!

Hi Everyone! Thanks to several people for presenting interesting mini-cases ranging from purple urine bag syndrome to nail clipper ingestion. Thanks to Sam and Satvik for presenting a case of a middle-aged man presenting with shortness of breath and found to have likely influenza and PCP! Eek! We discussed PCP treatment as well as CNS antibiotic penetration. Pearls below! Happy holidays!!

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Top Pearls:

  1. Preferred treatment for PCP PNA is TMP-SMX x 21 days, which has increased survival in severe disease compared to 2nd line IV pentamidine.
  2. In patients with a prior reaction to sulfa limited to the skin, it is reasonable to attempt desensitization to TMP-SMX.
  3. In addition to the usual empiric regimen of vancomycin + ceftriaxone +/- ampicillin for bacterial meningitis, other antibiotics that achieve good CNS penetration include cefepime, meropenem, aztreonam, and TMP-SMX.

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For those who want more info:

  • PCP PNA typically occurs in HIV patients with CD4 <200 off ARVs/ppx
  • Mortality is high in severe disease, >20% if A-a gradient >45, and as high as 60% in patients admitted to the ICU!

Treatment by disease severity:

  • Mild = A-a gradient <35 or PaO2 >70 (1st line tx = PO TMP-SMX)
  • Moderate = A-a gradient 35-45 or PaO2 60-70 (1st line tx = PO TMP-SMX + steroids)
  • Severe = A=a gradient >45 or PaO2 <60, or respiratory fatigue (1st line tx = IV TMP-SMX + steroids)

2015 Cochrane review confirmed significantly improved survival with steroids in HIV patients with PCP PNA and hypoxemia at presentation: risk ratio for overall mortality = 0.56 at 1 month and 0.59 at 3 months (NNT = 23 in settings where HAART available).

Treatment regimens:

Preferred tx is TMP-SMX x 21 days, improved survival in severe disease compared to 2nd choice IV pentamidine (86% vs. 61% in Ann Intern Med. 1988;109(4):280). Steroid taper typically also given over 21 days when indicated, starting at 40 mg BID and tapering to 20 mg daily.

Alternative regimens:

Pentamidine IV (2nd line for severe disease, up to 70% of patients experience side effects)

Primaquine + clindamycin (3rd line for severe disease, test for G6PD deficiency!)

TMP + dapsone (test for G6PD deficiency!) **Dapsone alone is used for PCP ppx but not treatment.

Atovaquone (used primarily in mild disease)

What about sulfa allergic patients?

  • Alternative therapies as above, or…
  • TMP-SMX desensitization! In patients with a history of isolated cutaneous reaction to sulfa, may attempt to desensitize using gradual dose escalation. This should be overlapped with an alternative regimen until treatment dose is achieved.

Restart ARVs within 2 weeks of PCP treatment initiation (significant reduction in risk of AIDS progression and death compared to waiting longer than 2 weeks).

**See these prior pearls from ZSFG and Moffitt on PCP:

ZSFG: https://ucsfmed.wordpress.com/2016/04/06/sfgh-4-5-am-report-pearls-pcppneumonia/

Moffitt: https://ucsfmed.wordpress.com/2015/07/16/moffitt-am-report-pearls-715-pcp-pneumonia/

 

CNS penetration of abx:

Good choices for empiric coverage of bacterial meningitis are ceftriaxone or cefotaxime (in addition to vancomycin +/- ampicillin).

Broader coverage can be achieved in immunocompromised or healthcare associated meningitis by substituting cefepime or meropenem for the 3rd generation cephalosporin.

**Imipenem should not be used for meningitis due to CNS toxicity, and ertapenem lacks sufficient data for meningitis use.

In patients with a beta-lactam allergy, aztreonam or moxifloxacin can substitute for the cephalosporin and TMP-SMX can substitute for Listeria coverage if needed.

Penicillins achieve therapeutic doses in the CNS in meningitis (including zosyn), but are not considered 1st line drugs in this setting (except ampicillin for Listeria as noted above).

Take-home: Stick with the usual empiric regimen of vancomycin + ceftriaxone +/- ampicillin, with cefepime or meropenem available as broader options that achieve good CNS penetration (*always discuss dosing with pharmacy if unsure!). Aztreonam is a good option in penicillin-allergic patients.

 

Evernote: https://www.evernote.com/shard/s272/sh/38c85d24-acbb-4e77-9c5f-7239dab06c03/aa544c862da79c2263252ed121a7f45c

Have a great day everyone!

SamMy

 

Filed under: Infectious Disease, Morning Report

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