Skin and soft tissue infections (SSTIs) cover a broad range of infectious processes including wounds, abscesses, skin structure, cellulitis, erysipelas, furuncles, burns, carbuncles, impetigo, and a variety of animal bite infections.1 The successful management of both community-associated and hospital associated SSTI involves accurate diagnosis, source control, laboratory microbiological support, and as needed appropriate antimicrobial regimens either empirical or directed post culture and susceptibility testing.1–3

Irrespective of anatomical site, the bacterial etiology of SSTI most frequently involves two species of Gram-positive cocci namely Staphylococcus aureus and β-hemolytic streptococci as well as various members of the family Enterobacteriaceae and Pseudomonas aeruginosa, and rarely anaerobes.4–6

Surgical drainage/debridement as well as antimicrobial therapy remains the mainstay of appropriate SSTI management. However, increasing global antimicrobial resistance in both Gram-positive and Gram-negative pathogens including those associated with SSTI has complicated both empirical and directed antimicrobial therapy.1 Prevalence studies have shown that over 50% of SSTI are caused by S. aureus including methicillin-resistant S. aureus (MRSA) thus greatly reducing the inherent or preferred use of a β-lactam for potential S. aureus SSTI.7,8 The CDC considers MRSA a serious threat with over 80,000 severe MRSA infections per year and an unknown but much higher number of less severe infections including SSTI.9

Over the past 15 years antimicrobials with activity against MRSA including vancomycin, daptomycin, tigecycline, and linezolid have been available, but each of these has therapeutic limitations and may not on their own provide coverage of polymicrobial infections that include Gram-negative pathogens. In the face of increasing antimicrobial resistance the search for new antimicrobials with activity against a variety of pathogens has led to the development and marketing of ceftaroline fosamil, a new broad-spectrum parenteral cephalosporin. Ceftaroline, the active metabolite of ceftaroline fosamil, inhibits penicillin-binding protein 2a of MRSA and shows effective activity against MRSA as well as against other Gram-positive cocci, and several species of Enterobacteriaceae (excluding those that produce extended-spectrum β-lactamases [ESBLs] or inducible AmpC β-lactamases).10,11 Prior in vitro susceptibility studies provide support of ceftaroline activity against many Gram-positive and commonly isolated Gram-negative pathogens.12–19

The AWARE (Assessing Worldwide Antimicrobial Resistance Evaluation) global surveillance program was established to monitor the susceptibility of pathogens to ceftaroline as well as relevant comparator antimicrobials to pathogens associated with SSTI as well as lower respiratory tract infection pathogens and complicated urinary tract infections in many areas of the world including Latin America. This report summarizes the data from SSTI pathogens from the AWARE program in Latin America in 2012.

In 2012 the 17 participating medical centers in Latin America contributed 1142 clinical isolates. The majority of isolates, both Gram-positive and Gram-negative, came from four main infection sources: wound (44%), abscess (26%), cellulitis (10%), and skin ulcers (9%). All other infection sites contributed ≤4% of isolates.

The susceptibility of various Gram-positive cocci to ceftaroline and relevant comparators is provided in Table 1. Against 696 S. aureus isolates (methicillin susceptible [MSSA] and MRSA isolates combined) the ceftaroline MIC90 was 1mg/L with 90.7% of all isolates susceptible. Only tigecycline and minocycline demonstrated lower MIC90 values of 0.5mg/L. S. aureus isolates irrespective of methicillin phenotype were susceptible to daptomycin, linezolid, tigecycline, and vancomycin. 100% of MSSA were susceptible to ceftaroline with an MIC90 of 0.25mg/L and 83.3% of MRSA susceptible to ceftaroline with MIC90 of 2mg/L. No MRSA were identified with an MIC >2mg/L (Table 1).

Variations in MIC90 for ceftaroline against MRSA were relatively minor with ranges from 0.5mg/L in isolates from Venezuela to 2mg/L in isolates from Brazil, Chile, and Colombia. Ceftaroline MICs for MSSA isolates displayed minimal variation (0.06–0.5mg/L) with MIC90 of 0.25mg/L irrespective of country (Table 2). All β-hemolytic streptococci (Streptococcus agalactiae, Streptococcus dysgalactiae, and Streptococcus pyogenes) were susceptible to ceftaroline with MIC90 ranges of 0.008–0.015mg/L (Table 1) with 55/56 S. pyogenes ceftaroline MIC90 of ≤0.008mg/L in all countries studied (Table 2). Isolates were 100 percent susceptible to most comparators with the exception of clindamycin and erythromycin where susceptibility ranged from 84.0 to 96.4%.

The activity of ceftaroline and comparators is shown in Table 3 for relevant Gram-negative bacilli where n>10. MIC90/% susceptible for ceftaroline by species were: Citrobacter freundii (64/64.3%), Citrobacter spp. (16/75%), Enterobacter aerogenes (32/83.3%), Enterobacter cloacae (>128/54.2%), E. coli (>128/50.0%), K. oxytoca (>128/76.5%), K. pneumoniae (>128/46.6%), Morganella morganii (64/50.0%), and Proteus mirabilis (>128/75%). For most Gram-negative bacilli examined tigecycline, piperacillin-tazobactam, amikacin, and meropenem displayed the highest percent susceptible ranging from 91 to 100% susceptible with the exception of K. pneumoniae. The MIC frequency distributions of ceftaroline against both ESBL screen-positive and ESBL screen-negative E. coli, K. pneumoniae, and K. oxytoca are shown in Tables 4–5. For all six Latin American countries combined the ceftaroline MIC90 was >128mg/L for all 86 E. coli with 50% of isolates susceptible at the CLSI breakpoint of 0.5mg/L (Table 4). Ceftaroline was not active against ESBL screen-positive E. coli isolates with all isolates demonstrating MICs ≥8mg/L. However for ESBL screen-negative isolates the MIC90 was 0.5mg/L with 95% of isolates susceptible. Two ESBL screen-negative E. coli isolates (one each from Argentina and Colombia) were resistant to ceftaroline with MICs of 2mg/L. The MIC frequency distribution of ceftaroline against 58 K. pneumoniae from all Latin American countries is shown in Table 5. MIC90 values were >128mg/L with only 48% of isolates susceptible at the CLSI breakpoint of 0.5mg/L. All 31 ESBL screen positive isolates were resistant to ceftaroline, whereas all ESBL screen-negative isolates were fully susceptible to ceftaroline. The MIC90 of ceftaroline for all Latin American K. oxytoca isolates (17) was >128mg/L with 76.5% susceptible at 0.5mg/L (data not shown). Only three ESBL screen-positive isolates were identified from this region: Chile (one) and Venezuela (two) with MIC values of >128mg/L. For the ESBL screen-negative isolates the MIC90 was 0.5mg/L with only one isolate from Argentina for which the ceftaroline MIC was 4mg/L.

All MSSA and all isolates of β-hemolytic streptococci in this study of SSTI major pathogens in Latin America were susceptible to ceftaroline (Table 1). This analysis confirms prior reports from Europe,15 Latin America,12,13 and the United States14 that include MSSA isolates not only from SSTI but lower respiratory tract infections. Of the MRSA isolates collected from SSTI in Latin America 9.3% were identified as ceftaroline intermediate (MIC 2mg/L) and none of MRSA isolates were ceftaroline resistant (MIC>2mg/L). The present study again demonstrated that whereas ceftaroline resistance in MRSA is uncommon geographical and regional variances can alter the overall susceptibility of MRSA to ceftaroline.12,19 Ceftaroline exhibited potent activity against ESBL screen-negative E. coli, K. pneumoniae and K. oxytoca in the present study as has been previously shown in several surveillance studies in various geographical areas.12–18 However ceftaroline had minimal in vitro activity against ESBL screen-positive Enterobacteriaceae SSTI isolates studied in this 2012 surveillance study in Latin America. All surveillance studies have limitations including isolate collection and data analysis. The AWARE surveillance study is not a prevalence of infection study nor a direct marker of phenotype prevalence as pathogen collection is dictated by rigorous study protocols. However, organism identification and susceptibility testing and interpretation are rigorously followed with comprehensive quality control in place.

In conclusion ceftaroline has been shown in this study and in prior surveillance studies to exhibit potent activity against MSSA and as a β-lactam agent potent activity against MRSA as well as β-hemolytic streptococci and ESBL screen-negative E. coli, K. pneumoniae, and K. oxytoca. SSTI currently represents one of the most common community and hospital associated infections globally and the need for new antimicrobials with activity against the most common pathogens associated with SSTI will need to continue to evolve. Ceftaroline represents one such newer antimicrobial with documented in vitro activity against the critical SSTI pathogens tested in this study from Latin America.

This study at IHMA was supported by AstraZeneca Pharmaceuticals LP, which also included compensation fees for services in relation to preparing the manuscript. DJH, DJB, and DFS are employees of International Health Management Associates, Inc. None of the IHMA authors have personal financial interests in the sponsor of this paper (AstraZeneca Pharmaceuticals). ER and JPI are employees of AstraZeneca.