EUAST Expert Rules for 2018 Organisms Agents tested Agents affected Rule aureus Oxacillin efoxitin (disk diffusion), detection of meca or mec gene or of PBP2a All β-lactams except those specifically licensed to treat infections caused by methicillin-resistant staphylococci due to low affinity for PBP2a IF resistant to isoxazolylpenicillins (as determined with cefoxitin, or by detection of meca/ -gene or of PBP2a) THEN report as resistant to all β-lactams except those specifically licensed to treat infections caused by methicillinresistant staphylococci due to low affinity for PBP2a; IF cefoxitin screening test negative AND oxacillin MI > 4 mg/l THEN check for BORSA by additional tests if clinically indicated IF cefoxitin screen test negative AND oxacillin MI < 4 THEN report as susceptible to all indicated ß- lactams Exceptions, scientific basis and comments Production of PBP2a leads to cross resistance to β-lactams except ceftobiprole and ceftaroline; susceptibility to cefoxitin indicates absence of this PBP. Rare strain occur that show an elevated MI to oxacillin despite beeing susceptible to cefoxitin. These strains may be BORSA and there are clinical situations where these may need additional testing. Strains with resistance to cefoxitin but susceptibility to oxacillin may harbour mec.(skov et al., 2014) Evidence grade Ref A [12, 14] Page 1
aureus and S. lugdunensis Benzylpenicillin (and β-lactamase detection) Erythromycin Penicillins apart from isoxazolyl-penicillins and combinations with β-lactamase inhibitors Azithromycin, clarithromycin, roxithromycin IF resistant to benzylpenicillin or IF β- lactamase is detected, THEN report as resistant to all penicillins, regardless of MI, except the isoxazolylpenicillins and combinations with β-lactamase inhibitors. IF susceptible, intermediate or resistant to erythromycin, THEN report the same category of susceptibility for azithromycin, clarithromycin, roxithromycin. Testing of β-lactamase production with nitrocefin is discouraged. The appearance of the zone edge is more reliable. Erythromycin is the class representative for 14- and 15-membered ring macrolides. Resistance to erythromycin is generally due to the production of a ribosomal methylase encoded by erm genes conferring the macrolidelincosamidestreptogramin B (MLS B ) phenotype or by production of an efflux pump. In both cases, there is cross-resistance between erythromycin and the other 14- and 15- membered ring macrolides. Page 2
Erythromycin, IF resistant to erythromycin AND susceptible to THEN test for inducible MLS B resistance; IF negative THEN report susceptible; IF positive THEN report resistant. Staphylococci and streptococci resistant to macrolides but susceptible to produce Erm ribosomal methylases conferring the inducible MLS B phenotype or express efflux pumps. In case of inducible MLS B resistance, constitutively resistant mutants can be selected by. Adding a note may be considered which states that may still be used in less severe skin and soft tissue infections. For ß- hemolytic streptococci a note may be considered that may be used in combinations when reduction of toxin synthesis is desired, such as streptococcal fasciitis. A Page 3
erythromycin ER.Staphylococci IF susceptible to erythromycin AND intermediate OR resistant to THEN report as tested. Norfloxacin All fluoroquinolones IF screening test with norfloxacin is negative ( susceptible ) THEN isolate can be reported susceptible to ciprofloxacin, levofloxacin and moxifloxacin; IF screening test positive ( resistant ) THEN individual agents must be tested Rare strains of staphylococci may produce an enzyme that inactivates lincosamides (lina or lnua) including. The enzyme does not affect macrolides. The screening test detects first step mutants and other mechanisms (e.g. efflux) that cause reduced susceptibility. Since mutants with increased efflux may still be susceptible to other fluroquinolones these must be tested. (Hori, Ohshita, Utsui, & Hiramats u, 1993; Kaatz & Seo, 1997) Ofloxacin, ciprofloxacin, levofloxacin, moxifloxacin, All fluoroquinolones IF resistant to ciprofloxacin, but susceptible to levofloxacin or moxifloxacin, THEN report with a warning of risk for development of resistance during therapy with quinolones. Acquisition of at least one target mutation in grla. (J M Sierra et al., 2005) Page 4
Levofloxacin, moxifloxacin All fluoroquinolones Staphylococci Tetracycline doxycycline, minocycline, tigecycline IF resistant to levofloxacin or moxifloxacin, THEN report as resistant to all fluoroquinolones. IF susceptible to tetracycline THEN report as susceptible to doxycycline, minocycline, tigecycline Acquisition of combined mutations in grla and gyra leads to complete or partial cross resistance to all fluoroquinolones. implicit rule from breakpoint table (J M Sierra et al., 2005) Staphylococci Linezolid tedizolid IF susceptible to linezolid THEN report as susceptible to tedizolid implicit rule from breakpoint table Page 5