Newer Antibiotics for Acute Skin Infections

Skin and soft-tissue infections (SSTIs) or Acute bacterial skin and skin-structure infections (ABSSSIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections.

Two terms are used interchangeably in literature but according to FDA, ABSSSIs include cellulitis/erysipelas, wound infection, and major cutaneous abscess with a minimum lesion surface area of 75 cm 2.

SCOPE OF PROBLEM

Acute bacterial skin and skin structure infections (ABSSSI) are among the most common infections observed in the emergency department. More than 15% of patients who present to the emergency department with an ABSSSI are admitted to the hospital, and the average hospitalization costs per patient range from $6300 to $13,000, with multi day room and board expenses comprising 50% of the total costs of care.

Mortality rate of patients hospitalized for ABSSSI was 0.5%.

TREATMENT GUIDELINES

Infectious Diseases Society of America (IDSA) published practice guidelines for the diagnosis and management of ABSSSIs in 2014.  World Society of Emergency Surgery (WSES) and the Surgical Infection Society Europe (SIS-E) issued their recommendations in 2018.

Several antibiotics were approved by FDA after publication of the IDSA guidelines, including dalbavancin, oritavancin, tedizolid, and delafloxacin.

SUMMARY OF IDSA GUIDELINES

 

NEWER ANTIBIOTICS

Following are the newer antibiotics for ABSSSI

Attribute Dalbavancin Oritavancin Tedizolid Delafloxacin LEFAMULIN

 

Mechanism of action Bactericidal,

Lipoglycopeptide

 

 

long plasma half-life

(6–10 days)

Bactericidal,

Lipoglycopeptide

 

long elimination half-life

Oxazolidione antibiotic; action is mediated by binding to the 50S subunit of the bacterial ribosome, resulting in inhibition of protein synthesis Improved

Cellular  transmembrane penetration and potency in acidic environments.  Delafloxacin targets both topoisomerase IV and DNA gyrase. Bactericidal

 

Bacteriostatic, Binding to the

peptidyl transferase center of the 50S ribosomal

subunit

Semisynthetic Pleuromutilin

 

INDICATIONS ABSSSI caused by susceptible strains of

gram-positive microorganisms

ABSSSI caused by susceptible strains of

gram-positive microorganisms

ABSSSI caused by susceptible strains of

gram-positive microorganisms

ABSSSI caused by susceptible strains of

gram-positive and gram-negative

microorganisms

ABSSSI caused by susceptible strains of

gram-positive skin

pathogens

IV form available Yes Yes Yes Yes Yes
Oral form available No No Yes Yes Yes
No dosing adjustment No No yes Yes ?
Common side effect nausea,

diarrhea, and pruritis

nausea, headache, and vomiting Nausea , Headache ,

Diarrhea

Diarrhea,

Nausea

Diarrhea,

Vomiting

?

 

Trial Comparison with vancomycin followed by oral linezolid Vancomycin Linezolid vancomycin plus aztreonam vancomycin
Dosing Single-dose regimen: 1500 mg IV over 30 min

Two-dose regimen: 1000 mg IV over 30 min followed

1 week later by 500 mg IV over 30 min

Single-dose regimen:

1200 mg IV

over 3 hours

200 mg IV/oral tablet

daily for 6 days;

IV infusion over 1 hour

300 mg IV over 60 min every 12 hours for

5–14 days

OR

450 mg oral tablet every 12 hours for 5–14 days

600 mg oral and 150 mg iv