Ceftaroline + Avibactam Effective Against Resistant Acute Bacterial SSSI Isolates

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SAN DIEGO, CA— Ceftaroline plus avibactam has wide-ranging in vitro bactericidal activity against resistant acute bacterial skin and skin structure infections clinical isolates, according to susceptibility testing presented by Helio Sader, MD, PhD, from JMI Laboratories, North Liberty, IA, at IDWeek 2012.

Ceftaroline is a broad-spectrum cephalosporin. It has demonstrated bactericidal activity against gram-positive cocci (including MRSA), as well as common Enterobacteriaceae. Avibactam is an innovative non-β-lactam/β-lactamase inhibitor of Ambler class A and C enzymes, as well as some Ambler class D enzymes.

A total of 6,648 isolates were collected in 2011 from 67 medical centers in the United States, characterizing all nine Census Regions (4–10 centers sampled/region). Susceptibility testing for ceftaroline plus avibactam (4mg/mL of avibactam), ceftaroline, and their comparators was conducted via Clinical Laboratory and Standards Institute broth microdilution processes.

The most common isolated organisms included: S. aureus (2,898 isolates; 51.5% of which was MRSA), β-hemolytic streptococci (1,233 isolates), E. coli (440 isolates; 12.7% of which was extended-spectrum beta-lactamase phenotype), Klebsiella species (409 isolates; 16.6% of which was extended-spectrum beta-lactamase phenotype and 5.4% of which was meropenem non-susceptible), coagulase-negative staphylococci (340 isolates), viridans group streptococci (264 isolates) and Enterobacter species (188 isolates; 18.1% of which was ceftazidime non-susceptible).

Ceftaroline plus avibactam exhibited 16 times more activity than ceftriaxone against methicillin-susceptible S. aureus. All MRSA was inhibited at ≤2μg/mL by ceftaroline plus avibactam (MIC50/90 0.5/1μg/mL). β-hemolytic streptococci, viridans group streptococci, and coagulase-negative staphylococci were all ceftaroline plus avibactam susceptible; their MIC90 values were ≤0.03, 0.06, and 0.5μg/mL, respectively. The activity of ceftaroline against gram-positive cocci was not negatively affected by the addition of avibactam.

All E. coli, including extended-spectrum beta-lactamase isolates, were inhibited at ceftaroline + avibactam MIC values of ≤0.5μg/mL. Ceftaroline plus avibactam was also active against Klebsiella species (MIC90 0.12μg/mL); this incorporates extended-spectrum beta-lactamase and meropenem-non-susceptible isolates (MIC90 1μg/mL for each). The highest ceftaroline plus avibactam MIC among ceftazidime-non-susceptible Enterobacter species was 1μg/mL.

“Ceftaroline-avibactam and ceftaroline were the most potent beta-lactam agents tested against staphylococci and streptococci collected from patients with skin and skin structure infections in the USA hospitals evaluated in [this] study,” Dr. Sader noted.

Ceftaroline plus avibactam was highly effective against Enterobacteriaceae-producing Klebsiella pneumoniae carbapenemases, numerous extended-spectrum beta-lactamases, and AmpC enzymes (chromosomal- or plasmid-mediated).

“In summary, ceftaroline plus avibactam demonstrated very potent in vitro efficacy against resistant Gram-positive and -negative pathogens associated with skin and skin structure infections in the USA,” Dr. Sader concluded.

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