1367 - Reduced Ceftaroline Susceptibility Among Invasive MRSA Isolates at a Tertiary Children’s HospitalReduced Ceftaroline Susceptibility Among Invasive MRSA Isolates at a Tertiary Children’s Hospital

Background: The emergence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) in the late 1990s-early 2000s complicated the empiric management of suspected staphylococcal infection in children.  Rising clindamycin resistance rates in many communities adds further to management challenges.  Ceftaroline, an anti-MRSA cephalosporin, represents an attractive therapy option.  Little data are available, however, regarding the frequency of reduced susceptibility (RS) to ceftaroline among MRSA isolates from a general pediatric population.

Methods: Isolates were selected from an ongoing S. aureus surveillance study at Texas Children’s Hospital.  Invasive MRSA isolates from 2015-2018 were included.  Isolates were initially screened for ceftaroline RS with E-test; all isolates with a ceftaroline E-test MIC ≥ 1.5µg/ml underwent ceftaroline broth dilution.  Ceftaroline RS was regarded as an MIC ≥ 2 µg/ml; full ceftaroline resistance was defined as an MIC ≥ 8 μg/ml.  Accessory gene regulator (agr) groups were characterized by PCR. 

Results: 201 viable isolates were included.  The ceftaroline MIC₅₀ and MIC₉₀ were 0.5 and 1 µg/ml, respectively (Figure 1).  Six isolates had MIC ≥ 2 µg/ml (2.9%) with two having MIC ≥ 8 µg/ml (0.9%).  All ceftaroline RS isolates were from healthcare associated infections.  Ceftaroline RS isolates were more often associated with clindamycin-resistance and agr group II (Figure 2).     Infections with ceftaroline RS were associated with central venous lines, recent ICU admission, preceding antibiotic exposure (specifically cephalosporins) and prior MRSA infection.  One subject with MRSA CLABSI had a ceftaroline susceptible MRSA infection followed < 1 month later by a ceftaroline resistant infection (MIC =32 μg/ml); the isolates were identical by PFGE.  Only 3 subjects had previously received ceftaroline, none of which subsequently developed a ceftaroline RS isolate. Figure 1. Ceftaroline MIC Distribution
Figure 2. Clinical And Microbiologic Associations with Reduced Ceftaroline Susceptibility


Conclusion: Ceftaroline RS occurs in 2.9% of invasive MRSA isolates in children and is most prominent among healthcare-associated infections.  These isolates were associated with clindamycin resistance and agr group II.  While ceftaroline RS is rare among invasive MRSA infections, the lack of preceding ceftaroline exposure is concerning and warrants careful surveillance.