Gram-Positive Antibiotics (IP4: Exam 1)

Chlorhexidine brand name:

• BetaSept

• Dyna-Hex

Chlorhexidine pharmacological class:

• Skin disinfectant

• Cationic bisbiguanide (ionic surfactant)

Chlorhexidine dosage form:

Topical antiseptic

An antiseptic is...?

Applied to living tissues to kill microorganisms

Chlorhexidine indication:

Used to disinfect skin for treatment of gram-positive skin and soft tissue infections

Chlorhexidine should not be used IV or ingested. Why?

• It is poorly absorbed via the GI tract and leads to mild irritation.

• When given IV, it can cause hemolysis or acute respiratory distress syndrome.

P-chloroaniline (metabolite of chlorhexidine in the bloodstream) causes...?

Methemoglobinemia

Mupirocin brand name:

• Bactroban

• Centany AT

Mupirocin pharmacological class:

• Decolonizing agent

• Derived from pseudomonas acids

Mupirocin dosage form:

Topical antibiotic ONLY

Mupirocin MOA:

inhibits bacterial protein synthesis by reversible binding and inhibition of isoleucine-tRNA synthase

Mupirocin resistance mechanism:

plasmids encodes a bypass isoleucine-tRNA synthase that binds mupirocin poorly (similar to mecA gene)

Mupirocin spectrum of action:

• gram-positive bacteria (staph and strep mainly)

• some gram-negative bacteria

Retapamulin brand name:

Altabax

Retapamulin pharmacological class:

• Semisynthetic pleuromutilin

• Nasal decolonizing agent

Retapamulin dosage form:

Topical 1% ointment

Retapamulin MOA:

binds to the 50S ribosomal subunit to inhibit peptide translation

Retapamulin spectrum of action:

• gram positive aerobes (e.g. strep and staph

• potential use as a nasal decolonizing agent for treatment of mupirocin-resistant MRSA

Lefamulin brand name:

Xenleta

Lefamulin pharmacological class:

Pleuromutilin antibiotic

Lefamulin dosage form:

PO and IV

Lefamulin MoA:

inhibits peptide synthesis via binding to the 50S ribosomal subunit

Lefamulin spectrum of action:

• Treatment of community-acquired pneumoniae (CAP)

• Potent, broad-spectrum activity (gram-positive, gram-negative and atypicals)

• Roughly equivalent to moxifloxacin

Rifampicin brand name:

Rifadin

Rifampicin pharmacological class:

Antibioitic

Rifampicin dosage form:

Oral

Rifampicin MOA:

• inhibits DNA-dependent RNA polymerase transcription

• penetrates gram-positive biofilms

Rifampicin spectrum of action:

• backbone of RIPE (antimycobacterial therapy)

• adjuvant to a primary antistaphylococcal agent (like MRSA and osteomyelitis)

What is important to remember about Rifampicin?

• It is a potent CYP3A4 inducer

• It should be taken on an empty stomach

• It may turn a patient's tears or urine red

Rifabutin brand name:

Mycobutin

Rifabutin pharmacological class:

antibiotic

Rifabutin dosage form:

oral

Rifabutin MoA:

penetrates biofilms

Rifabutin spectrum of action:

inhibits staphylococcus at MICs lower than Rifampicin

Rifapentine brand name:

Priftin

Rifapentine pharmacological class:

structural analog of Rifampin

Rifapentine dosage form:

oral

Rifapentine MoA:

similar to Rifampicin (can be administered less frequently)

Rifapentine spectrum of action:

similar to Rifampicin

What happens when Rifapentine is taken with food?

AUC increases by 50%

Why are Rifamycin drugs not used as monotherapy?

RBOP (RNA polymerase targets) are susceptible to overnight mutations that cause resistance

Dalfopristin/Quinupristin brand name:

Synercid

Dalfopristin/Quinupristin pharmacological class:

Streptogramins

Dalfopristin/Quinupristin dosage form:

IV via a central line

Dalfopristin/Quinupristin MOA:

• bind to different sites of the 50S ribosomal subunit and inhibit peptide elongation

• individually the drugs are bacteriostatic, but together, they are bactericidal (gram-positive killers)

• inhibit CYP3A4 (drug-drug interactions)

Dalfopristin/Quinupristin spectrum of action:

• MRSA

• VRSA

• vanco-resistant E. faecium

  • primary indication, second line treatment

Streptogramins must be mixed and administered with…

• 5% dextrose in water solution (D5W)

• streptogramins will precipitate out of solution in saline