Viridans group streptococci in febrile neutropenic cancer patients: what should we fear?

In this issue of Clinical Infectious Diseases, Shelburne et al report their development and validation of a clinical prediction model for β-lactam resistance in viridans group streptococci (VGS) causing bloodstream infection (BSI) and offer guidance for the use of vancomycin (or gram-positive spectrum antibiotics) for empiric therapy of febrile neutropenia (FN) [1]. Although VGS cause a significant minority of BSIs in FN patients, they are associated with a shock syndrome (VGSS) and/or acute respiratory distress syndrome (ARDS) in 7%–39% of patients, with mortality rates ranging from 2% to 21% [2–9]. VGSS/ARDS was initially described in the 1990s and linked to the presence of profound neutropenia, oral mucositis , high-dose chemotherapy, and also to fluoroquinolone or trimethoprim-sulfamethoxazole prophylaxis and ceftazidime empiric therapy for FN [5, 6, 8, 10, 11]. Poor in vitro activity against Streptococcus mitis, the most common cause of VGSS/ARDS, is characteristic of these antibiotics. Latergeneration expanded-spectrum β-lactams with more reliable activity against VGS (and other gram-positive pathogens) have largely supplanted ceftazidime for empirical antibiotic monotherapy and include cefepime, piperacillin-tazobactam, and the antipseudomonal carbapenems, imipenem and meropenem [12, 13]. Increasingly, however, VGS bearing diminished susceptibility to penicillin and to the newer β-lactams are being recognized [2, 6, 10, 11]. These β-lactam resistant isolates primarily concern Shelburne et al as potentially causing rapid and disastrous complications from VGS bacteremia in patients with FN. Driving this study is the thought that improved outcomes (eg, lower incidence of VGSS/ARDS and mortality) will be afforded to FN patients with β-lactam– resistant VGS bacteremia if they receive vancomycin (or gram-positive antibiotics) as part of the empiric β-lactam– based regimen. In 1997, Spanik et al observed higher mortality rates in FN patients with penicillin-resistant VGS bacteremia, while in another study published in the same year, Elting et al reported increased mortality in FN patients who did not receive vancomycin initially for documented α-hemolytic streptococcal BSI [8, 10]. Both studies largely included patients treated with fluoroquinolone prophylaxis and ceftazidime therapy, 2 important risks for VGSS/ARDS. Fueled by these reports, some practitioners have reflexively added vancomycin to the empiric β-lactam regimen for all patients with FN, presuming that it will prevent the potentially life-threatening effects of VGS BSI. Indeed, at the MD Anderson Cancer Center, where Shelburne et al conducted their study, a stunning 96% of all patients with FN in their validation cohort (2011– 2013) received vancomycin as part of the empiric therapy. In contrast, the 2010 Infectious Diseases Society of America (IDSA) guidelines recommend much stricter criteria for empiric vancomycin use, suggesting it be limited to FN patients with hemodynamic instability or other evidence of severe sepsis (an indicator for possible VGSS), documented gram-positive BSI prior to identification, skin and soft tissue infection, or pneumonia, or to those with known colonization or suspected infection due to β-lactam– nonsusceptible organisms (eg, methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae) [12]. Although the IDSA guidelines recognize VGS BSI as a cause of shock and ARDS, there is no recommendation for broadly adding empiric vancomycin to an initial antipseudomonal Received 17 March 2014; accepted 20 March 2014; electronically published 21 April 2014. Correspondence: Alison Freifeld, MD, University of Nebraska Medical Center, Omaha, NE 68198-5400 (afreifeld@unmc. edu). Clinical Infectious Diseases 2014;59(2):231–3 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/ciu264