Neuro Antibiotics Flashcards by Sarah Gillen

Metronidazole is a prodrug that is active against anaerobic bacteria and anaerobic protozoal microorganisms.

What is its MOA?

Anaerobic microorganisms contain electron transport components that have high enough negative redox potential to donate electrons to metronidazole

When an electron is donated to metronidazole, a highly reactive nitro radical anion is formed. This ion mediates the killing of susceptible organisms by radial-mediated DNA damage

Note that Mitronidazole can be catalytically recycled by losing the added electron, allowing it to move back and forth between active and inactive state

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Primary mechanism of metronidazole resistance

Resistance to metronidazole correlates with impaired O2 scavenging, which leads to increased intracellular O2 levels and decreased activation of the drug

[increased O2 levels promote recycling of active nitro radical back to inactive metronidazole form]

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What are some specific organisms that metronidazole is active against?

In general, active against anaerobes

T.vaginalis
G.lamblia
E.histolytica (protozoan)

Helicobacter species
Campylobacter species

Gram-positive bacilli such as Clostridium species

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Adverse effects of mitronidazole

Unique adverse effects include metallic taste in the mouth and disulfiram-like effects - meaning that vomiting may be induced if patient ingests alcohol within 3 days of taking metronidazole

Other common adverse effects include dry mouth, nausea, and headache

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Pathogen(s) implicated in neonates with acute pyogenic meningitis

E.coli

Group B streptococci

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Pathogen(s) implicated in infants with acute pyogenic meningitis

H.influenzae

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Pathogen(s) implicated in adolescents/young adults with acute pyogenic meningitis

N.meningiditis

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Pathogen(s) implicated in elderly with acute pyogenic meningitis

S.pneumoniae

L.monocytogenes

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Standard empiric treatment for acute pyogenic meningitis

[Cefotaxime or Ceftriaxone] + Vancomycin

Add ampicillin in older patients (>50 years)

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How would you treat acute pyogenic meningitis in a patient with a beta-lactam allergy?

Vancomycin + moxifloxacin

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How would you treat acute pyogenic meningitis in a patient over 50 with a beta-lactam allergy?

Vancomycin + moxifloxacin + TMP/SMX

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How would you treat acute pyogenic meningitis in an immunocompromised patient?

Vancomycin + ampicillin + [cefepime or meropenem]

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Pathogens most often implicated in acute aseptic (viral) meningitis

Enteroviruses (coxsackievirus, echovirus)

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How would you treat a case of meningitis if it is unclear as to whether it is a bacterial or viral cause?

Start antibiotics soon after lumbar puncture, and send CSF for culture

If bacterial cultures are negative, then discontinue abx

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Most common pathogens implicated in brain abscess

Strep viridans

Staph aureus

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An antibiotic for brain abscess is chosen based upon origin of abscess and probable pathogen involved.

What is the empiric therapy of brain abscess wtih an unknown source?

Vancomycin + [ceftriaxone or cefotaxime] + metronidazole

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Medication used for brain abscess that covers aerobic and anaerobic streptococci (mouth flora)

Penicillin G

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Medication used for brain abscesses that readily penetrates the abscess and is typically combined with other agents

Metronidazole

Medication used for brain abscesses that covers most aerobic and microaerophilic streptococci; it may be used as a substitute for penicillin G, covers many enterobacteriaceae, and is interchangeable with cefotaxime

Ceftriaxone

Antibiotics often used if a brain abscess complicates a neurosurgical procedure, as well as covers cases in which the abscess culture grows P.aeruginosa

Ceftazidime, cefepime, or meropenem

No MRSA = No vancomycin.

What 2 abx may be substituted for vancomycin?

Nafcillin

Oxacillin

Pathogens implicated in subdural empyema

Aerobic and anaerobic streptococci, staphylococci, enterobacteriaceae, and anaerobic bacteria

[subdural empyema following neurosurgical procedures or head trauma are often staphylococci and gram-negative bacilli]

33% of cases are culture negative

Subdural empyemas are medical emergencies. Surgery is performed to evacuate the empyema, followed by antibiotic therapy.

What is the empiric therapy for community acquired vs. hospital acquired (p.aeruginosa or MRSA) subdural empyema?

Community acquired:
[Cefotaxime or ceftriaxone] + vancomycin + metronidazole

Hospital acquired:
Meropenem + vancomycin

Describe live attenuated vaccines in terms of duration of immunity, strength of protection, Ig produced, interrupting viral spread, and potential for reversion

Longer duration of immunity
Greater strength of protection
Produces IgA and IgG + cell-mediated immunity
More effective at interrupting spread
Reversion to virulence is possible

Describe killed virus (subunit) vaccines in terms of duration of immunity, strength of protection, Ig produced, interrupting viral spread, and potential for reversion

``` Shorter duration of immunity Lower strength of protection Produces IgG + weak/no cell-mediated immunity Less effective at interrupting spread No potential for reversion to virulence ```

What type of vaccine is the MMR?

Live attenuated

What type of poliomyelitis vaccine do we receive in the USA?

IPV = killed virus vaccine — does NOT cause vaccine-associated paralytic polio OPV is a live attenuated oral version that is used in other countries - can cause polio in a small percentage of individuals

Pathogen most often implicated in fungal meningoencephalitis

Cryptococcal meningitis (note that this is often in the setting of AIDS - CD4 < 100 cells/ul)

What medications are chosen for the induction phase and consolidation phase of treating fungal meningoencephalitis?

Induction phase: Amphotericin B + flucytosine Consolidation phase: Fluconazole

Most anti-fungal agents bind ______ with a higher affinity than cholesterol, allowing for selective toxicity as this is a vital part of the cell membranes of fungi and not found in the cell membranes of humans

Ergosterol

MOA of amphotericin B

Forms a complex with ergosterol and disrupts the fungal cell membrane Leads to cytoplasmic leakage and fungal cell death

Adverse effects of amphotericin B

Renal toxicity Acute febrile reaction (chills+fever) Anemia

MOA of flucytosine (5-FC)

Antimetabolite; converted to 5-FU inside fungal cells which inhibits DNA and RNA synthesis

Adverse effects of flucytosine (5-FC)

Conversion of 5-FC to 5-FU outside the fungal cell Bone marrow depression, nausea, vomiting, diarrhea Note that rapid resistance develops if used alone

MOA of fluconazole

Inhibits ergosterol synthesis by inhibiting fungal P450 enzymes Has very good CNS penetration and adverse effects are limited

What anti-fungal medication has the widest therapeutic index of all the azoles?

Fluconazole

T/F: you can use clindamycin to treat neuroinfections

FALSE

What 1st gen. Cephalosporins must you avoid using to treat neuroinfections?

Cefazolin

What aminoglycosides must you avoid using to treat neuroinfections?

``` Streptomycin Gentamicin Tobramycin Amikacin Neomycin Paromomycin Kanamycin Netilmicin ```

What tetracyclines must you avoid using to treat neuroinfections?

Doxycycline Tetracycline Minocycline Demeclocycline

What macrolides must you avoid using to treat neuroinfections?

Erythromycin Clarithromycin Azithromycin Fidaxomicin

A 32-year-old female presents to clinic with complaints of headache with joint and muscle pain. The patient admits that the pain has persisted for the past 2 days. Physical examination reveals nuchal rigidity. A gram stain of her spinal fluid shows many neutrophils and many gram-negative, bean shaped diplococci. Which of the following pharmacological agents would be best to treat this patient’s infection? ``` A. Tetracycline B. Cefotaxime + vancomycin C. Erythromycin D. Metronidazole E. Meropenem + ampicillin + vancomycin ```

B. Cefotaxime + vancomycin [note that E would be the choice for an immunocompromised pt]

A 32-year-old female presents to clinic with complaints of headache with joint and muscle pain. The patient admits that the pain has persisted for the past 2 days. Physical examination reveals nuchal rigidity. A gram stain of her spinal fluid shows many neutrophils and many gram-negative, bean shaped diplococci. The patients medical history reveals an allergy to beta-lactam antibiotics. In combination with vancomycin, which of the following would be best to treat this patient’s infection? ``` A. Ceftriaxone + ampicillin B. Cefotaxime C. Moxifloxacin + TMP/SMX D. Moxifloxacin E. Meropenem + ampicillin ```

D. Moxifloxacin

A 31-year-old male presents to the Emergency Department with fever (102.4ºF, 39.1ºC), headache, confusion, muddled thinking, and vomiting. The patient’s medical history reveals a diagnosis of HIV/AIDS with a last known CD4 cell count of 90 cells/µL. Physical examination reveals nuchal rigidity and photophobia. An India ink stain of the spinal fluid shows budding organisms. Which of the following treatment options would be best for this patient? ``` A. Fluconazole B. Clindamycin C. Colistin D. Ampicillin + erythromycin E. Amphotericin B + flucytosine ```

E. Amphotericin B + flucytosine