Viridans Group Streptococcal Infections Among Children With Cancer and the Importance of Emerging Antibiotic Resistance

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Viridans group streptococci (VGS) are major pathogens among children with cancer or receiving hematopoietic stem cell transplantation and are associated with considerable morbidity and mortality rates. The incidence and severity of VGS infections have increased during the past 15 years and account for as many as one third of all bacteremic episodes. Risk factors include severe neutropenia, mucositis, gastrointestinal toxicity, pneumonia, younger age, and high-intensity chemotherapy (especially cytosine arabinoside). VGS no longer can be assumed to be susceptible to penicillin because as many as 37 percent of VGS isolates harbor high levels of resistance (minimum inhibitory concentration >4 μg/mL). Furthermore, resistance to multiple classes of antibiotics, including β-lactams and fluoroquinolones, has now been documented and is increasing in prevalence. In this article, we present a brief overview of VGS, describe the clinical spectrum of VGS-related diseases in children with cancer, and review the recent data regarding the incidence, clinical significance, and management of emerging antibiotic resistance among VGS.

Section snippets

Microorganisms

The viridans streptococci are a group of gram-positive cocci belonging to the genus Streptococcus. The number of species comprising the viridans group is large and somewhat cumbersome because of the fact that certain of the commonly identified organisms can be separated into additional species if carefully analyzed by biochemical and molecular means.7 For example, what once was identified as Streptococcus mutans now can be shown to actually be six unique but closely related species:

Pathogenesis and Risk Factors

VGS are most prevalent in the oral cavity and can be part of the normal bacterial flora of the gastrointestinal tract, the female genital tract, and, occasionally, the skin flora. Among immunocompromised patients, damaged oral mucosa appears to be the major portal of entry for the development of VGS bacteremia.30 Interactions between VGS and the oral mucosa and dental surfaces promote binding and help to establish colonization of these microbes within the mouth and gastrointestinal tract. When

Empiric Therapy for Fever and Neutropenia

Several recent studies have demonstrated an association between infections with penicillin-resistant VGS and increased mortality rates. Docze and coworkers, in a national surveillance study of streptococcal bacteremia in Slovakia, found that death occurred in 69 percent of cases with penicillin-resistant VGS isolates versus only 21 percent of cases with nonsusceptible isolates (P < 0.0002).52 Spanik and coworkers found that infection of cancer patients with penicillin-resistant VGS strains was

Summary

VGS infections among children with cancer are increasing in incidence and severity, and the emergence of antibiotic resistance has rendered treatment of these infections even more problematic. Penicillin resistance among VGS has developed to an extent that now warrants antimicrobial susceptibility testing of all clinically relevant VGS isolates. Current data support the use of vancomycin as part of the empiric antibiotic regimen for febrile neutropenia in children who are seriously ill or when

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