Chapter 130. Streptococcal and Enterococcal Infections (Part 12) Enterococci may be resistant to penicillins via two distinct mechanisms. The first is β-lactamase production (mediating resistance to penicillin and ampicillin), which has been reported for E. faecalis isolates from several locations in the United States and other countries. Because the amount of β-lactamase produced may be insufficient for detection by routine antibiotic susceptibility testing, isolates from serious infections should be screened specifically for β- lactamase production with a chromogenic cephalosporin or another method. For the treatment of β-lactamase–producing strains, vancomycin, ampicillin/sulbactam, amoxicillin/clavulanate, imipenem, or meropenem may be used in combination with gentamicin. The second mechanism of penicillin resistance is not mediated by β- lactamase and may be due to altered penicillin-binding proteins. This intrinsic penicillin resistance is common among E. faecium isolates, which routinely are more resistant to β-lactam antibiotics than are isolates of E. faecalis. Moderately resistant enterococci (MICs of penicillin and ampicillin, 16–64 µg/mL) may be susceptible to high-dose penicillin or ampicillin plus gentamicin, but strains with MICs of ≥200 µg/mL must be considered resistant to clinically achievable levels of β-lactam antibiotics, including imipenem and meropenem. Vancomycin plus gentamicin is the recommended regimen for infections due to enterococci with high-level intrinsic resistance to β-lactams. Vancomycin-resistant enterococci (VRE), first reported from clinical sources in the late 1980s, have become common in many hospitals. Three major vancomycin resistance phenotypes have been described: VanA, VanB, and VanC. The VanA phenotype is associated with high-level resistance to vancomycin and to teicoplanin, a related glycopeptide antibiotic not currently available in the United States. VanB and VanC strains are resistant to vancomycin but susceptible to teicoplanin, although teicoplanin resistance may develop during treatment in VanB strains. For enterococci resistant to both vancomycin and β-lactams, no established therapies provide uniformly bactericidal activity. Two newer agents active against VRE are quinupristin/dalfopristin and linezolid, which were approved for use in the United States in 1999 and 2000, respectively. Quinupristin/dalfopristin is a streptogramin combination with in vitro bacteriostatic activity against E. faecium, including VRE, but not against E. faecalis or other enterococcal species. Disadvantages of quinupristin/dalfopristin are its limited spectrum of activity against enterococcal species and its relatively frequent side effects of phlebitis and myalgia. Linezolid is an oxazolidinone antibiotic with good bacteriostatic activity against nearly all enterococci, including VRE. Limited clinical experience suggests that linezolid is at least as efficacious as quinupristin/dalfopristin, and linezolid is usually preferred because of its broader activity against all enterococci and the availability of both parenteral and oral formulations. Bone marrow toxicity (especially thrombocytopenia) and peripheral neuropathy are potential side effects. Two other antibiotics are active in vitro against VRE (both E. faecalis and E. faecium), although neither had been approved for treatment of these infections as of May 2006: daptomycin, a cyclic lipopeptide, and tigecycline, a glycylcycline related to tetracycline. Other Group D Streptococci The main nonenterococcal group D streptococcal species that causes human infections is S. bovis. S. bovis endocarditis is often associated with neoplasms of the gastrointestinal tract—most frequently, a colon carcinoma or polyp—but is also reported in association with other bowel lesions. When occult gastrointestinal lesions are carefully sought, abnormalities are found in ≥60% of patients with S. bovis endocarditis. In contrast to the enterococci, nonenterococcal group D streptococci like S. bovis are reliably killed by penicillin as a single agent, and penicillin is the agent of choice for S. bovis infections. Viridans and Other Streptococci Viridans Streptococci Consisting of multiple species of α-hemolytic streptococci, the viridans streptococci are a heterogeneous group of organisms that are important agents of bacterial endocarditis (Chap. 118). Several species of viridans streptococci, including S. salivarius, S. mitis, S. sanguis, and S. mutans, are part of the normal flora of the mouth, where they live in close association with the teeth and gingiva. Some species contribute to the development of dental caries. Previously known as S. morbillorum, Gemella morbillorum has been placed in a separate genus, along with G. haemolysans, on the basis of genetic-relatedness studies. These species resemble viridans streptococci with respect to habitat in the human host and associated infections. The transient viridans streptococcal bacteremia induced by eating, tooth- brushing, flossing, and other sources of minor trauma, together with adherence to biologic surfaces, is thought to account for the predilection of these organisms to cause endocarditis (see Fig. 118-1). Viridans streptococci are also isolated, often as part of a mixed flora, from sites of sinusitis, brain abscess, and liver abscess. Viridans streptococcal bacteremia occurs relatively frequently in neutropenic patients, particularly after bone marrow transplantation or high-dose chemotherapy for cancer. Some of these patients develop a sepsis syndrome with high fever and shock. Risk factors for viridans streptococcal bacteremia include chemotherapy with high-dose cytosine arabinoside, prior treatment with trimethoprim-sulfamethoxazole or a fluoroquinolone, treatment with antacids or histamine antagonists, mucositis, and profound neutropenia. The S. milleri group (also referred to as the S. intermedius or S. anginosus group) includes three species that cause human disease: S. intermedius, S. anginosus, and S. constellatus. These organisms are often considered viridans streptococci, although they differ somewhat from other viridans streptococci in both their hemolytic pattern (they may be α-, β-, or nonhemolytic) and the disease syndromes they cause. This group commonly produces suppurative infections, particularly abscesses of brain and abdominal viscera, and infections related to the oral cavity or respiratory tract, such as peritonsillar abscess, lung abscess, and empyema. . Chapter 130. Streptococcal and Enterococcal Infections (Part 12) Enterococci may be resistant to penicillins via two distinct. β-, or nonhemolytic) and the disease syndromes they cause. This group commonly produces suppurative infections, particularly abscesses of brain and abdominal viscera, and infections related to. these infections as of May 2006: daptomycin, a cyclic lipopeptide, and tigecycline, a glycylcycline related to tetracycline. Other Group D Streptococci The main nonenterococcal group D streptococcal