Gram Positive Antibiotics

Chlorhexidine Route of Administration

Topical

Chlorhexidine Indication

• Chlorhexidine is an antiseptic used to disinfect skin for treatment of gram-positive skin and soft-tissue infections 

• Skin cleanser 

• Mouthwash  

Mupirocin Route of administration

Topical (skin ointment, intranasal)

Mupirocin Indications

Skin and soft tissue infections caused by: 

• Staphylococcus aureus (MSSA & MRSA) 

• Streptococcus pyogenes 

Nasal decolonization of S. aureus (Bactroban Nasal®) 

Name the Pleuromutilins

Retapamulin and Lefamulin

Retapamulin  Route of Administratin

Topical

Retapamulin Indication

• Impetigo caused by susceptible gram-positive organisms 

• Active against S. aureus and S. pyogenes 

• Potential role in mupirocin-resistant MRSA nasal decolonization 

Lefamulin Route of Administration

Oral and IV

Lefamulin Indications

• Community-acquired pneumonia (CAP) 

Coverage includes: 

• Gram-positive: S. aureus, S. pneumoniae, VRE faecalis 

• Atypicals: Chlamydia, Legionella 

• Gram-negative: H. influenzae, M. catarrhalis 

What are the Rifamycins

Rifampicin, Rifabutin, Rifapentine

Rifampicin Route of Administration

Oral

Rifampicin Indications

• Backbone of antimycobacterial (TB) therapy 

• Adjunct therapy for gram-positive infections 

• Prosthetic joint infections 

• Osteomyelitis 

• Penetration of gram-positive biofilms 

• Special counseling: Red-orange discoloration of urine and tears 

Rifabutin Route of Administration

Oral

Rifabutin Indication

• Similar to rifampicin 

• Preferred in patients on multidrug regimens due to fewer CYP interactions 

• Key feature: More potent against staphylococci at lower MICs 

Rifapentine Route of Administration

Oral

Rifapentine Indications

• Similar spectrum to rifampicin 

• Allows less frequent dosing due to longer half-life 

• Key feature: Increased AUC when taken with food 

Name the Streptogramins

Quinupristin/Dalfopristin 

Quinupristin/Dalfopristin Route of Administration

IV only (central line; D5W only)

Quinupristin/Dalfopristin Indications

• Vancomycin-resistant Enterococcus faecium (VRE) 

• Resistant gram-positive infections 

• Place in therapy: Second-line due to toxicity and better alternatives available 

Describe the mechanism of action for rifampicin, rifabutin, and rifapentine

Mechanism of Action: 

• Inhibit DNA-dependent RNA polymerase 

• Block transcription 

• Prevent bacterial RNA synthesis 

Result: Bactericidal activity 

Clinical significance: 

• Active against dormant bacteria 

• Penetrates biofilms 

• Resistance develops rapidly if used alone → used as adjunct therapy 

Describe the Mechanism of Action for Quinupristin/Dalfopristin (Streptogramins) 

Mechanism of Action: 

• Bind to different sites on the 50S ribosomal subunit 

• Inhibit peptide elongation 

Pharmacodynamic effect: 

• Each drug alone = bacteriostatic 

• Combined = synergistic bactericidal activity 

Spectrum focus: Resistant gram-positive organisms