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Antimicrobial Susceptibility - Bacteremic Staphylococcal Infections with Strains Having Elevated Glycopeptide (Vancomycin) Mic Values

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Antimicrobial Susceptibility - Bacteremic Staphylococcal Infections with Strains Having Elevated Glycopeptide (Vancomycin) Mic Values ANTIMICROBIAL SUSCEPTIBILITY - BACTEREMIC STAPHYLOCOCCAL INFECTIONS WITH STRAINS HAVING ELEVATED GLYCOPEPTIDE (VANCOMYCIN) MIC VALUES This specimen was presented as a blood culture (bacteremia) isolate and was to be identified and tested for antimicrobial susceptibility. The culture contained a Staphylococcus epidermidis, a common isolate from blood cultures, some being considered skin contaminates. High rates of methicillin resistance are observed in coagulase-negative staphylococci (CoNS) such as S. epidermidis, thus requiring therapy with alternative agents such as vancomycin. This strain was selected to highlight the importance of accurate assessment of vancomycin activity, especially those strains at the extreme (MIC, 4 µg/ml) of the wildtype MIC distribution. The strain was distributed by API to survey participants as an Educational Sample (ES) challenge and susceptibility testing specimen. Participant grading was not applied. Responses were S. epidermidis (83.6%); Staphylococcus, coagulase-negative (13.9%); aerobic growth, referred (1.0%); Gram-positive aerobe (0.4%); aerobic growth referred/Gram-positive aerobe (0.1%); and S. epidermidis, methicillin- resistant (0.1%). The overall accuracy rate was at 99.1%. Organism Identification (ID) S. epidermidis is a Gram positive, coagulase negative member of the Staphylococcaceae family.1 Gram stain characteristics of S. epidermidis are typical of other members of Staphylococcaceae and will appear as Gram positive cocci that occur singly, in pairs, tetrads, short chains and grapelike clusters. The morphology of S. epidermidis when cultured on sheep blood agar plates often appears as a nonpigmented, smooth, glistening, and opaque colony of 2.5 to 6 mm diameter. Common identification characteristics that all S. epidermidis strains share are 1) inability to produce coagulase, 2) ability to grow anaerobically using standardized medium containing glucose, and 3) inability to ferment mannitol anaerobically. The key biochemical test for S. epidermidis is the coagulase test. The slide coagulase test using rabbit plasma can be performed to detect the presence of bound coagulase also known as "clumping factor". This result will be negative for S. epidermidis and present as a homogenous suspension after 10 seconds. A negative slide test should be confirmed with a tube coagulase test to detect the presence of bound and free coagulase. The tube coagulase test will result in a homogenous suspension (no clot formation) after 4 and 24 hours incubation for S. epidermidis. A positive catalase test (15% H2O2 concentration) will differentiate staphylococci isolates from enterococci. Proper technique is needed when performing the catalase test from colonies grown on blood agar to avoid false-positive results. Most commercially available automated identification systems can reliably identify S. epidermidis. When a CoNS isolate is recovered from a blood culture or other sterile body site, it is important to attempt to determine the identification to the species level. Differentiating a true CoNS bacteremic infection from a contaminate can be challenging. However, when a CoNS is isolated from two different blood draw sites or grows rapidly, with high intensity or from multiple samples, the probability of a true infection increases. American Proficiency Institute – 2012 2nd Test Event ANTIMICROBIAL SUSCEPTIBILITY - BACTEREMIC STAPHYLOCOCCAL INFECTIONS WITH STRAINS HAVING ELEVATED GLYCOPEPTIDE (VANCOMYCIN) MIC VALUES (cont.) Clinical Setting and Site of Infection CoNS, particularly S. epidermidis, are among the most important pathogens involved in hospital- associated bloodstream infections. In the 2011 USA SENTRY Antimicrobial Surveillance Program, CoNS was the 5th most common organism isolated (5.7%) from bloodstream infections, and S. epidermidis represented approximately two-thirds of the speciated CoNS isolates. S. epidermidis is ubiquitous to healthy human skin and mucosal surfaces, readily colonizing newborns and remaining part of the normal microflora throughout life.2 S. epidermidis and other CoNS have long been regarded as culture contaminants but their important role as true pathogens and their increasing incidence have been recognized for many years.3,4 However, the clinical significance of a positive blood culture for CoNS may be difficult to assess. Various clinical and laboratory definitions have been proposed to differentiate true infection from contamination, and the most commonly used requires at least two positive blood cultures collected from two different venous sampling sites.5 CoNS rarely causes infections in healthy tissue,6 but has a pronounced ability to proliferate on surfaces of indwelling medical devices after surgical insertion,7 where it forms persistent multilayered agglomerations called biofilms. Because of these characteristics, CoNS are undoubtedly the most common cause of bacteremia related to indwelling devices and most of these infections are hospital-acquired. Other important infections caused by CoNS include central nervous system shunt infections, native or prosthetic valve endocarditis, urinary tract infections, bone and joint infections and endophthalmitis.8 CoNS infections are characterized by their indolence and usually require the removal of the catheter or device to achieve cure. CoNS exhibit a high rate of methicillin resistance (76.4% in the global SENTRY Program, 2002-2010)9 and resistance to multiple other antimicrobial agents further complicates treatment of systemic infections. Although CoNS are usually susceptible to glycopeptides, increased MIC values for teicoplanin (29.9% at ≥4 μg/ml)9 and/or vancomycin (43.1% at ≥2 μg/ml)9 are being more frequently reported and may be related to poor clinical outcome.10,11 A recent retrospective study on MRSA bacteremia showed that patients with poor response to glycopeptide therapy (defined as persistent or a recurrent bloodstream infection episode) had 2.8- and 4.8-fold higher rates of isolates displaying elevated teicoplanin or vancomycin MICs (≥4 µg/ml), respectively, when compared to those patients with a favorable clinical response.12 Specific therapies for invasive CoNS infections may include vancomycin or linezolid or daptomycin with gentamicin or rifampicin added to prevent the emergence of resistance or to enhance bactericidal activity. More recently, the oxyimino cephalosporin ceftaroline was approved by the US Food and Drug Administration for treatment infections caused by S. aureus, including MRSA, and may represent a valuable option for treatment of CoNS infection.13 American Proficiency Institute – 2012 2nd Test Event ANTIMICROBIAL SUSCEPTIBILITY - BACTEREMIC STAPHYLOCOCCAL INFECTIONS WITH STRAINS HAVING ELEVATED GLYCOPEPTIDE (VANCOMYCIN) MIC VALUES (cont.) Antimicrobial Susceptibility Testing (Ungraded) Participants were asked to perform antimicrobial susceptibility testing on this S. epidermidis. This strain was selected to challenge proper identification and to determine antimicrobial susceptibility across numerous classes of agents, especially the Gram positive active antimicrobials. The initial reference laboratory antimicrobial susceptibility testing was conducted by standardized reference broth microdilution methods14 and susceptibility was determined based on CLSI document M100-S22, USA-FDA product package inserts or EUCAST breakpoints.15-17 The reference laboratory testing reported a total of 30 agents (Table 1) that exhibited activity varying from high potency (only eight drugs) to frank resistance (21 agents). Consensus categorical susceptibility accuracy data are found in Table 2 for 26 antimicrobials having a significant sample of participant responses. All listed drugs achieved a category consensus (≥80% of results or a reference test); but one agent (vancomycin), due to MIC results at or within one doubling dilution step of intermediate breakpoints, required two categories for analysis. Furthermore, three active agents (Table 1) were not reported by a significant number of participants (ceftaroline, doxycycline, telavancin). Quinupristin/dalfopristin was not tested by the reference method, but was susceptible at ≤1 µg/ml by consensus participant results. The acceptable performance by participants using the disk diffusion (DD) results18 ranged from 50.0% (cefazolin) to 100.0% (18 drugs). Lowest acceptable response rates were for some inactive β-lactams (50.0-66.7%) and rifampin (85.7%). Similarly, the commercial MIC system testing results had levels of acceptable performance at ≥98.3% (24 drugs), except for cefoxitin (80.0%; small sample at only 5 responses) and levofloxacin (76.0%). Nearly all (97.0%) of the incorrect levofloxacin intermediate results were generated by the Vitek 2 system. The vancomycin results are shown in Table 3 listed by method of origin. The reference MIC value of 4 µg/ml should be categorized as susceptible and were correctly reported by 50.0% (Sensititre) to 99.5% (MicroScan) of participants. However, if this organism was a S. aureus the correct category would be consistent with a VISA strain e.g. vancomycin-intermediate. Resistance Mechanisms Although a commensal, CoNS acquired in the community are usually more susceptible, but those recovered from hospitalized patients often display a greater resistance phenotype to methicillin (oxacillin) and other anti-staphylococcal agents, except for vancomycin, teicoplanin, tigecycline, linezolid, and daptomycin.9,19 However, isolates exhibiting decreased susceptibility to glycopeptides have been reported in the
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