Emergence of Erythromycin- and Clindamycin-Resistant Streptococcus pyogenes emm 90 Strains in Hawaii

Abstract

We identified 12 erythromycin-and clindamycin-resistant emm 90 group A streptococcus (GAS) isolates during a retrospective invasive disease survey in Hawaii. A comparison with 20 type-matched isolates showed all resistant isolates to be emm 90.4b with the constitutive or inducible macrolide-lincosamide-streptogramin B resistance phenotype (cMLS B or iMLS B ). All isolates had the same pulsed-field gel electrophoresis (PFGE) pattern, suggesting clonal spread.The erythromycin resistance rate (ϳ3%) has been low among group A streptococcus (GAS) isolates in Hawaii, where impetigo, acute rheumatic fever, and clusters of necrotizing fasciitis have been reported (5-7, 8-10; G. Erdem, G. Matsuura, G. Wheelen, C. Mizumoto, D. Esaki, and P. V. Effler, presented at the XVIIth Lancefield International Symposium on Streptococci and Streptococcal Diseases, Porto Heli, Greece, 2008). During a retrospective survey of 250 GAS cultures collected from patients with invasive GAS disease identified between the years 2005 and 2007, the reviews of the clinical information incidentally showed erythromycin and clindamycin resistance in five patients. emm typing of these isolates showed a single emm type: emm 90.4b. In addition to these five isolates, 15 additional isolates from individual patients with invasive disease were emm type 90.4b. The high percentage of invasive isolates (8%) belonging to this infrequent emm type and associated drug resistance prompted us to characterize the associated drug resistance patterns. We wanted to compare the resistance patterns among the isolates identified during this survey and other emm type 90 isolates identified from patients with noninvasive disease during our previous surveys. Of the 20 invasive GAS isolates, 12 were from blood cultures. Eight isolates were identified from wound cultures of inpatients with severe skin and soft tissue infections. Twelve additional emm type 90 pharyngeal isolates from our archived collection of 1,660 GAS isolates (collected from 1997 to 2007) were studied.(Preliminary data were presented in part at the American Society of Tropical Medicine and Hygiene 58th Annual Meeting in November 2009.) emm sequencing (http://www.cdc.gov/ncidod/biotech/strep /strepblast.htm) was done for all isolates. Etest methodology (AB Biodisk, Piscataway, NJ) was used to determine MICs for erythromycin and clindamycin (2, 3). The erythromycin-clindamycin double disk test was applied to resistant isolates. The "blunting" in the inhibition zone around the clindamycin disk next to the erythromycin disk was interpreted to be an inducible macrolide-lincosamide-streptogramin B resistance phenotype (iMLS B ), and susceptibility to clindamycin with no blunting indicated the M phenotype. The mef(A), erm(B), erm(A) (20), and erm(TR) resistance genes and prtF1 were detected by PCR amplification (11,19,23,24,26,27). Pulsed-field gel electrophoresis (PFGE) was performed with a Chef-DR III apparatus (Bio-Rad) after SmaI digestion.All (20 isolates showing resistance to both clindamycin (MIC, 3 to 4 g/m...

Human polyspecific immunoglobulin attenuates group A streptococcal virulence factor activity and reduces disease severity in a murine necrotizing fasciitis model

“…Mortality in NF patients has remained high despite state-of-theart treatment, including b-lactams and protein synthesis inhibitors such as clindamycin. Although emergence of clindamycin-resistant strains has been observed [2,3], we recently showed that protein synthesis inhibitors efficiently inhibited virulence factor activity even in clindamycin-resistant GAS [15]. We now demonstrate that the inhibition of virulence factor activity by IVIG in clindamycinresistant GAS strains is equal to susceptible strains.…”

“…This high rate has not changed over time. Although no resistance to penicillin has yet been found, increasing numbers of clindamycin-resistant GAS strains are being reported [2,3].…”

Aminomethyl spectinomycins as therapeutics for drug-resistant respiratory tract and sexually transmitted bacterial infections

“…amSPCs were also potent inhibitors of S .pyogenes , which causes pharyngitis and necrotizing fasciitis and can be challenging to treat in patients allergic to betalactams due to increasing clindamycin and macrolide resistance (36-38). Since S. pneumoniae is a predominant cause of childhood upper respiratory tract infections and treatment is compromised by resistance to macrolides and betalactams, we focused our in vivo efforts on this pathogen.…”

Molecular characterization and evaluation of the emerging antibiotic-resistant Streptococcus pyogenes from eastern India

“…Association of erythromycin resistance and emm typing has been documented earlier. emm 12 from Korea and Japan [51], emm 12 and emm75 from Pittsburgh [52], emm 90 from Hawaii [53], emm 4, emm 28, and emm 77 from Western Greece [54] showed strong association with erythromycin resistance. In present study, association is different from earlier workers as emm 49 was constantly associated with the erythromycin resistance.…”