A 72- year old woman presented to a hospital emergency room after 5 days of malaise and fever. She had undergone extensive dental work 10 days prior to the onset of fever. Two years ago, she had received a prosthetic aortic valve implant. After examination of the patient and review of the patient's history, two sets of blood cultures were obtained and the patient was admitted to the hospital with the diagnosis of acute bacterial endocarditis. A transesophageal echocardiogram revealed a 4-mm vegetation on her mitral valve. The patient was started on a regimen of penicillin and gentamicin. Two days later, the laboratory reported growth of viridans group streptococci in both blood cultures. The isolate was tested on a broth microdilution MIC panel containing Mueller-Hinton broth with 2.5% lysed horse blood. After overnight incubation in ambient air, the following results were obtained:
| MIC (µg/ml) | Interpretation | | Cefotaxime | 1 | S | | Ceftriaxone | 1 | S | | Chloramphenicol | 4 | S | | Clindamycin | <0.25 | S | | Erythromycin | <0.25 | S | | Levofloxacin | <0.5 | S | | Penicillin | 1 | I | | Vancomycin | <0.5 | S | Note: Unlike for Streptococcus pneumoniae, for which trimethoprim-sulfamethoxazole is listed in Group A under "Primary Test and Report," there are no interpretive criteria available for trimethoprim-sulfamethoxazole for "Streptococcus spp. other than S. pneumoniae," so this drug should not be reported for viridians group streptococci. Question 1: Where is the best place to find information on the antimicrobial agents that should be tested and reported for viridans group streptococci? Table 1A of NCCLS document M100-S12 contains recommendations for the antimicrobial agents that should be tested and reported for non-pneumococcal streptococci; however, the guidelines do not address viridans group streptococci separately from beta-hemolytic streptococci. This may change in the next few years since distinct differences in the susceptibility patterns of viridans group streptococci and beta-hemolytic streptococci have emerged. The interpretive criteria for viridans group streptococci are listed in Table 2H "Streptococcus spp. other than S. pneumoniae." These criteria are distinct from those in Table 2G, which are specific for Streptococcus pneumoniae. The latter should not be used for viridans group streptococci. The American Heart Association (AHA) recommendations for the treatment of endocarditis caused by viridans group streptococci are keyed to the penicillin MIC of the infecting isolate. Patients infected with viridans group streptococci for which the penicillin MICs are very low (MIC <0.1 µg/ml) may be treated with penicillin alone. As the penicillin MIC for the isolate increases, the AHA recommendations suggest either adding gentamicin, switching the beta-lactam to ampicillin in combination with gentamicin, or using vancomycin and gentamicin (see below). These recommendations emphasize the need for the laboratory to report accurate and timely penicillin MIC results for viridans group streptococci, particularly for those isolates associated with endocarditis. AHA therapy guidelines for endocarditis due to viridans group streptococci | Penicillin MIC (µg/ml) | Suggested Therapy | | <0.1 | penicillin* +/- gentamicin; or ceftriaxone | | >0.1 - <0.5 | penicillin + gentamicin | | >0.5 | penicillin or ampicillin + gentamicin | | >4.0 | vancomycin +/- gentamicin | *Vancomycin is used in place of penicillin for the penicillin-allergic patient (alone or with gentamicin). Laboratories should consider reporting results for penicillin and vancomycin for viridans group streptococci isolated from blood. To date, vancomycin resistance has not been reported in any streptococcal species. Question 2: Are there comments suggested by NCCLS that may be useful to append to the susceptibility test report? Yes. Combination therapy for endocarditis is an important consideration for viridans group streptococci that are not susceptible to penicillin. NCCLS has an "Rx," or therapy, comment in document M100-S12 (Table 2H, comment 8, on page 114) that states "Penicillin- or ampicillin-intermediate isolates may require combined therapy with an aminoglycoside for bactericidal action." Depending on your institution's policies, this comment (or a modification of it) could be appended to a laboratory report as follows: | MIC (µg/ml) | Interpretation | | Penicillin 1 | I | | Vancomycin <0.5 | S | Report comment: Viridans group streptococci that are intermediate to penicillin may require combined therapy with an aminoglycoside to achieve bactericidal action. Question 3: Is it necessary to perform antimicrobial susceptibility tests on viridans group streptococci isolated from sources other than blood? Yes, if the isolates are recovered from normally sterile body sites in pure culture. In addition to endocarditis, viridans group streptococci may cause bacteremia, abscesses (particularly in the liver and brain), and serious dental infections. If cultures from normally sterile sites yield viridans group streptococci mixed with other bacteria (either aerobic and anaerobic), or if isolates are obtained from superficial skin lesions, susceptibility testing should not be performed, as the results may be misleading. An infectious disease consultation may be recommended in such cases. Question 4: Table 2H in NCCLS M100-S12 has separate MIC and disk diffusion interpretive criteria for cefepime, cefotaxime, ceftriaxone, and penicillin for beta group streptococci and viridans group streptococci. Why is this necessary? There have been no confirmed reports of resistance to cefepime, cefotaxime, ceftriaxone, or penicillin among the beta-hemolytic streptococci. Consequently, NCCLS has defined a "susceptible only " category for these drugs for beta-hemolytic streptococci. On the other hand, isolates of viridans group streptococci that are no longer penicillin susceptible have been recognized since the 1970s. The percentage of isolates that are no longer susceptible to penicillin has been reported to be as high as 50% in some regions of the world. Thus, interpretive criteria defining susceptible, intermediate, and resistant strains have been developed by NCCLS for viridans group streptococci and each of the four agents listed above. Question 5: Why are penicillin disk diffusion interpretive criteria listed for beta group streptococci but not for viridans group streptococci in NCCLS M100-S12? The penicillin disk diffusion test correctly categorizes all beta-hemolytic streptococci tested to date as susceptible. In contrast, the penicillin disk diffusion test is unable to distinguish penicillin-susceptible from penicillin-non-susceptible isolates of viridans group streptococci. Furthermore, the oxacillin disk screen test used to determine penicillin susceptibility in S. pneumoniae does not work for viridans group streptococci. A penicillin MIC test should be performed on viridans group streptococci isolated from patients with endocarditis or other serious infections as emphasized in NCCLS M100-S12. However, before using a commercial MIC system to test viridans group streptococci, make certain that it has been FDA-cleared for this purpose. Question 6: Is beta-lactamase testing ever useful for viridans group streptococci? No. Penicillin resistance in viridans group streptococci is due to altered penicillin-binding proteins and not to the production of beta-lactamase. As with S. pneumoniae, the beta-lactamase test cannot be used to detect penicillin resistance in viridans group streptococci. Question 7: Should results for an extended-spectrum cephalosporin be reported for viridans group streptococci? The decision to test and report extended-spectrum cephalosporins for isolates of viridans group streptococci that are not susceptible to penicillin depends on your institution. There is a comment in M100-S12 (Table 2H, comment 6, on page 114) that indicates penicillin-susceptible streptococci can be considered susceptible to other beta-lactam drugs. Consequently, penicillin-susceptible viridans group streptococci are considered susceptible to extended-spectrum cephalosporins (e.g., ceftriaxone). However, for isolates that are not penicillin susceptible (i.e., penicillin MICs >0.12 ug/ml), the extended-spectrum cephalosporin of interest should be tested. Viridans group streptococci that are not penicillin susceptible are often less susceptible to other beta-lactams as well. Question 8: Are the tests for high-level aminoglycoside resistance that are used to predict the synergy of aminoglycosides and cell wall-active agents for enterococci valid for viridans group streptococci? No. There are no standardized methods for aminoglycoside synergy testing of viridans group streptococci. Penicillin and gentamicin are believed to be synergistic and to exert a bactericidal effect against viridans group streptococci, provided that the isolate is not penicillin resistant. Rare isolates of viridans group streptococci demonstrating high-level aminoglycoside resistance have been reported; however, it is not clear that these organisms would be consistently detected with the high-level aminoglycoside resistance screening tests used for enterococci. If a physician requests synergy studies, it is suggested that he/she consult with an infectious diseases specialist. References: - Doern, G. V., M. J. Ferraro, A. Brueggemann, and K. L. Ruoff. 1996. Emergence of high rates of antimicrobial resistance among viridans group streptococci in the United States. Antimicrob. Agents Chemother. 40:891-894.
- Sanford, J. P., D. N. Gilbert, R. C. Moellering, Jr., and M. A. Sande. 2001. The Sanford Guide to Antimicrobial Therapy, 2001 ed. Antimicrobial Therapy, Inc., Hyde Park, VT.
- Tuohy, M., and J. Washington. 1997. Antimicrobial susceptibility of viridans group streptococci. Diagn. Microbiol. Infect. Dis. 29:277-280.
- Wilson, W. R., A. W. Karchmer, A. S. Dajani, K. A. Taubert, A. Bayer, D. Kaye, A. L. Bisno, P. Ferrieri, S. T. Shulman, and D. T. Durack. 1995. Antibiotic treatment of adults with infective endocarditis due to streptococci, enterococci, staphylococci, and HACEK microorganisms. J. Am. Med. Assn. 274:1706-1713.
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