Non-tuberculous mycobacterial infection in hospitalized children: a case series.

Non-tuberculous mycobacteria (NTM) illness is an emerging life-threatening infection, and paediatric features have not been well studied. The objective of our study was to review the NTM isolates of hospitalized paediatric patients identified at our institution and to describe the characteristics of these cases. Our retrospective chart review from 2010 to 2013 identified 45 patients with 46 positive NTM cultures. Fifteen (33%) patients had received haematopoietic cell transplant, 13 (29%) had cystic fibrosis, and six (13%) were previously healthy. Twenty-seven (59%) NTM isolates were Mycobacterium chelonae/abscessus, 14 (30%) were M. avium intracellulare, and four (9%) were M. immunogenum. The majority (65%) of cases were community-acquired, and 20 (43%) patients were treated as infection. This case series identified a predominance of M. chelonae/abscessus, and includes a substantial number of haematopoietic cell transplant patients, which reflects the changing spectrum of NTM disease as molecular diagnostics improve and quaternary care facilities provide for a larger immunocompromised population.

Biochemical and immunological characterization of the extracellular nucleases of group B streptococci.

Nearly all group B streptococcal strains representing the five major serotypes were found to produce extracellular nucleases by screening with an agar-well-diffusion technique in DNA-methyl green agar plates. Three different nucleases have been isolated and partially purified by DEAE-and carboxymethyl-cellulose chromatography. They possessed different mobilities on polyacrylamide gel electrophoresis and different molecular weights. These nucleases, designated I, II, and III, are optimally activated by cations of calcium and manganese and exhibited RNase as well as DNase activity. Despite differences in their physical and biochemical properties, nucleases II and III appear antigenically similar, but distinct from nuclease I. These group B streptococcal nucleases are immunologically different from the nucleases of group A streptococci. Neutralizing activity, probably antibody, to nucleases II and III was found in human sera, and was most prevalent in sera of pregnant women colonized with group B streptococci and in their newborn infants.

Natural history of impetigo. II. Etiologic agents and bacterial interactions.

Intensive observations on 37 children in a population with endemic skin infections provided an opportunity to study the interrelationships between and the significance of the bacterial genera commonly associated with impetigo. Cultures of the respiratory tract, three normal skin sites, and lesions, when present, were taken three times weekly from July to October 1969. Impetigo developed in all 37 children. Group A streptococci alone were recovered from 21% of 361 lesions, Staphylococcus aureus alone from 8%, Staphylococcus epidermidis alone from 5% and mixtures of streptococci and staphylococci from 61%. Vesicular or pustular lesions were more often pure streptococcal than pure staphylococcal. Streptococci alone were more often recovered from early stage lesions rather than from later ones. The pure staphylococcal lesions characteristically occurred early in the season whereas streptococcal or mixed lesions had later peaks.Serial observations on 74 lesions revealed longer persistence of streptococci than staphylococci in mixed lesions. In 85% of the instances the same streptococcal serotype was recovered repeatedly from an individual lesion, whereas staphylococcal types changed in 57% of instances. Phage type 75 accounted for the majority of staphylococcal isolates from all sites, whereas phage type 54 was recovered only from skin lesions. In contrast to streptococci, the site sequence of staphylococcal spread was from the nose to normal skin to skin lesions. These studies reveal important differences in the migration of staphylococci (as compared with streptococci) to various body sites and suggest a subsidiary role for staphylococci in nonbullous impetiginous lesions yielding both organisms.

Natural history of impetigo. I. Site sequence of acquisition and familial patterns of spread of cutaneous streptococci.

The appearance on and spread of Group A streptococci among different body sites in relationship to the development of impetigo were studied prospectively in 31 children in five families. During July and August 1969 intensive clinical, bacteriological, and serological observations were made, including cultures taken at least every other day. In individual children, site sequence of spread of Group A streptococci was from normal skin to lesions and finally to respiratory tract. Streptococci were recovered from normal skin before development of lesions (mean interval of 10 days) in 74% of episodes. Recovery of streptococci from nose and throat followed (by means of 14 and 20 days, respectively) skin acquisition of streptococci (97% of episodes) and lesions (74% of episodes).Distribution of positive normal skin sites among wrist, ankle, and back was similar (28-37%) although 62% of lesions were on the legs. Recovery of a serotype from normal skin was associated with a high risk (76%) of subsequent development of lesions due to that type. New streptococcal serotypes usually entered a family during the peak or decline of a preceding serotoype with a tendency of one to predominate. Among family members the mean interval from index to secondary skin acquisition of streptococci was 4.8 days, but 21 days elapsed from first appearance to last acquisition of skin disease. In the population as a whole, streptococci were recovered in high frequency from normal skin before the increase in prevalence of lesions and also later in the fall when cutaneous infections were absent.

Comparison of sequencing the D2 region of the large subunit ribosomal RNA gene (MicroSEQ®) versus the internal transcribed spacer (ITS) regions using two public databases for identification of common and uncommon clinically relevant fungal species.

CONTEXT: Fungal infections cause considerable morbidity and mortality in immunocompromised patients. Rapid and accurate identification of fungi is essential to guide accurately targeted antifungal therapy. With the advent of molecular methods, clinical laboratories can use new technologies to supplement traditional phenotypic identification of fungi. OBJECTIVE: The aims of the study were to evaluate the sole commercially available MicroSEQ® D2 LSU rDNA Fungal Identification Kit compared to the in-house developed internal transcribed spacer (ITS) regions assay in identifying moulds, using two well-known online public databases to analyze sequenced data. DESIGN: 85 common and uncommon clinically relevant fungi isolated from clinical specimens were sequenced for the D2 region of the large subunit (LSU) of ribosomal RNA (rRNA) gene with the MicroSEQ® Kit and the ITS regions with the in house developed assay. The generated sequenced data were analyzed with the online GenBank and MycoBank public databases. RESULTS: The D2 region of the LSU rRNA gene identified 89.4% or 92.9% of the 85 isolates to the genus level and the full ITS region (f-ITS) 96.5% or 100%, using GenBank or MycoBank, respectively, when compared to the consensus ID. When comparing species-level designations to the consensus ID, D2 region of the LSU rRNA gene aligned with 44.7% (38/85) or 52.9% (45/85) of these isolates in GenBank or MycoBank, respectively. By comparison, f-ITS possessed greater specificity, followed by ITS1, then ITS2 regions using GenBank or MycoBank. Using GenBank or MycoBank, D2 region of the LSU rRNA gene outperformed phenotypic based ID at the genus level. Comparing rates of ID between D2 region of the LSU rRNA gene and the ITS regions in GenBank or MycoBank at the species level against the consensus ID, f-ITS and ITS2 exceeded performance of the D2 region of the LSU rRNA gene, but ITS1 had similar performance to the D2 region of the LSU rRNA gene using MycoBank. CONCLUSION: Our results indicated that the MicroSEQ® D2 LSU rDNA Fungal Identification Kit was equivalent to the in-house developed ITS regions assay to identify fungi at the genus level. The MycoBank database gave a better curated database and thus allowed a better genus and species identification for both D2 region of the LSU rRNA gene and ITS regions.

Invasive Scopulariopsis in the immunocompromised host.

Opportunistic infections with fungal organisms have been well described in patients undergoing intensive chemotherapy and bone marrow transplantation. In two patients, invasive infections with the saprophyte Scopulariopsis developed either following intensive chemotherapy or bone marrow transplant. Fungal disease persisted in both patients despite resection of the primary focus and prolonged treatment with the usual antifungal agents, and contributed to the death of one patient.

Early-onset pneumococcal sepsis in newborn infants.

Five infants with pneumococcal sepsis presented with respiratory distress and clinical signs of infection in the first day of life. Although there was no apparent epidemiological relationship among the patients, four of the five were seen within a 12-month period. Pneumonia, prolonged rupture of fetal membranes, and prematurity were features in these patients. Three infants died, two within 12 hours of diagnosis. Streptococcus pneumoniae was isolated from the vagina of three of the mothers; in two, the serotype was identical to that recovered from their infants. Clinical features of neonatal pneumococcal sepsis are similar to those of early-onset group B streptococcal infection. Like the group B Streptococcus, S. pneumoniae acquired from the maternal vagina is a potential life-threatening pathogen in the newborn period.

Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association.

Primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis. Diagnosis of GAS pharyngitis is best accomplished by a throat culture. Penicillin (either oral penicillin V or injectable benzathine penicillin) remains the treatment of choice, because it is cost effective, has a narrow spectrum of activity, has long-standing proven efficacy, and GAS resistant to penicillin have not been documented. Various macrolides, oral cephalosporins, and other beta-lactam agents are acceptable alternatives, particularly in penicillin-allergic individuals. The individual who has had an attack of rheumatic fever is at very high risk of developing recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial prophylaxis to prevent such recurrences (secondary prevention). The duration of prophylaxis depends on the number of previous attacks, the time lapsed since the last attack, the risk of exposure to streptococcal infections, the age of the patient, and the presence or absence of cardiac involvement. Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or erythromycin are acceptable alternatives in penicillin-allergic individuals. This report is an update of a 1988 statement by this committee. It expands on the previous statement, includes more recent therapeutic modalities, and makes more specific recommendations for the duration of secondary prophylaxis.

Changing epidemiology of group B streptococcal colonization.

OBJECTIVES: To define factors influencing vertical transmission of and neonatal colonization with group B streptococci (GBS) in neonates representing ethnically and economically diverse populations, and to determine the serotype distribution of isolates, especially new types IV-VIII. STUDY DESIGN: Prospective, cross-sectional study of neonates born to women evaluated for GBS colonization at admission for delivery to one of four hospitals between January 1994 and February 1995. Cultures of throat, umbilicus, and rectum were obtained from 24- to 48-hour-old infants for isolation of GBS. Isolates were classified by capsular polysaccharide (I-VIII) and C protein (alpha and beta) antigen components. RESULTS: Colonization was detected in 28% of 546 mothers, was higher in blacks than whites (40.6% vs 20.3%) and Hispanics (26. 9%), and was not influenced by socioeconomic status. Overall, ethnic origin did not seem to be related to GBS serotype, but whites were more likely to carry the new type V strain than blacks (6 out of 24 [25%] vs 1 out of 43 [2%]). Vertical transmission of GBS to neonates was significantly diminished when their mothers had intrapartum antibiotics (0% vs 52%), rupture of membranes <12 hours before delivery (38.4% vs 73.3%), or delivery by cesarean section (25.9% vs 45.2%). Colonization with GBS was found in 13.8% of 549 neonates, was acquired vertically in 97%, and was less frequent in neonates at the private hospitals (4% vs 20%) where intrapartum antibiotics were given more frequently (34.7% vs 17.3%). Among isolates from neonates, serotype Ia predominated (31.6%) followed by types II (25%), III (22.4%), and V (11.8%); approximately 40% of strains contained C protein antigen. CONCLUSIONS: Changes in the epidemiology of GBS colonization included diminished rates in some populations associated with use of maternal intrapartum antibiotics, and a shift in serotype prevalence, with Ia as predominant and V, in addition to II and III, as common.

Systemic candidiasis in very low-birth-weight infants (less than 1,500 grams).

Previous reports in the literature have documented that systemic infection with Candida albicans in very premature infants is frequently fatal (54%) or associated with significant morbidity in survivors (25%). Five patients with a mean birth weight of 829 g had a diagnosis of systemic candidiasis during their stay in a newborn intensive care unit. All infants survived with minimal sequelae following aggressive early treatment with amphotericin B and 5-flucytosine. A review of these five extremely premature infants and 26 previously reported patients suggests the following: (1) disseminated candidiasis is common in the absence of positive findings in blood, CSF, and/or urine cultures; (2) transient candidemia rarely resolves without therapy; (3) meningitis and osteoarthritis occur more frequently than in older patients with disseminated disease; and (4) premature infants tolerate amphotericin B and 5-flucytosine well. Infants who are found to have systemic cultures positive for candidiasis should be treated by (1) removing all factors that predispose to systemic candidiasis (eg, indwelling catheters, broad-spectrum antibiotics); (2) early initiation of systemic antifungal therapy with amphotericin B and 5-flucytosine; and (3) searching for additional foci of disease. After the disease is recognized and treatment is prompt and aggressive, outcome can be substantially improved.

Antibody profiles to the group B streptococcal beta antigen in maternal and infant paired sera.

Antibody profiles to the purified beta antigen of the c protein of group B streptococci (GBS) were studied by ELISA and Western immunoblot (WB). The sera from 139 parturient women colonized with GBS, 35 non-colonized parturients and their newborn infants were studied by ELISA; WB was done on 76 maternal and 26 infant sera. Enzyme-labeled anti-IgA (alpha), -IgG (gamma), -IgM (mu), or -IgG (H&L) were used as secondary antibodies. A high prevalence of antibody to the beta antigen was observed by both ELISA and WB among parturient women and their newborns. IgG (H&L) ELISA titers > or = 200 were found in 84% and > or = 800 in 31% of the maternal sera. A significantly higher percentage of women colonized than those non-colonized with GBS had IgG (gamma) titers > or = 800. A significantly higher percentage of women colonized with c protein-positive than c-negative strains of GBS had IgG (H&L) titers > or = 3200. Twelve of 27 women with IgM antibody to the beta antigen also had IgG (gamma) titers > or = 800 and were, in addition, colonized with GBS. Multiple molecular forms of the antigen from 25 to 140 kDa were blotted by the maternal and infant sera. Concordance in the IgG but not in IgA or IgM antibody profiles of maternal and infant paired sera was observed in the overall blotting patterns and ELISA titers. The same titer as the mother was found in 55% of the infant sera and within one dilution in 97%. This suggests active transfer of IgG antibody to the beta antigen across the placenta from mother to baby.

Association of exotoxin-producing group A streptococci and severe disease in children.

Clinical features and microbiologic data on all cases of serious (hospitalized) Group A streptococcal infections in children managed at our institution between 1985 and 1988 are presented. All 6 cases were caused by toxin-producing strains. Four of 6 were toxin A-producing strains whereas none of 58 community-acquired (Group A streptococcal) pharyngeal isolates in the same period was a toxin A producer. A review of the literature on the incidence of toxin A-producing strains provides information suggesting a resurgence of such strains in the late 1980s after a relative disappearance of toxin B production in isolates from these patients was also significantly greater than in the isolates acquired from the community in uncomplicated pharyngitis. These findings suggest a role for exotoxin in severe manifestations of Group A streptococcal disease in children.

Correlation of clinical and pathologic findings in early onset neonatal group B streptococcal infection with disease severity and prediction of outcome.

This study analyzed the clinical characteristics of 69 neonates who were admitted to the University of Minnesota Hospital between January, 1972, and June, 1984, with early onset Group B streptococcal infection (EOGBS) and determined those features associated with fatal infection. The incidence of EOGBS was 1.6 cases/1000 live births among 7960 inborn infants; the mortality rate for inborn and outborn infants was 28%. Multivariate analysis identified five features adequately predicting fatal outcome: birth weight less than 2500 g, absolute neutrophil count less than 1500 cells/mm3, hypotension, apnea and a pleural effusion on the initial chest radiographs. With these five variables and an initial blood pH less than 7.25, a clinical score was constructed that correctly predicted outcome in 93% of patients in this study (87% sensitivity, 95% specificity). Autopsy findings in 16 of 19 infants with fatal EOGBS suggested that surfactant deficiency respiratory distress syndrome was common in preterm infants with EOGBS and contributed to their higher mortality compared with term infants.

The performance of gamma- and EtO-sterilised UHMWPE acetabular cups tested under severe simulator conditions. Part 2: wear particle characteristics with isolation protocols.

Ultra-high molecular-weight polyethylene (UHMWPE) has been used in total joint replacement for the last three decades. Despite the recent advancements in prosthesis design, the wear of UHMWPE remains a serious clinical problem; the release of wear debris may induce osteolysis and implant loosening. Controlling the quality of the polyethylene is essential to improve its wear resistance and any potential adverse effect caused by processing, manufacturing or sterilisation should be avoided. To evaluate the influence of the sterilisation method (gamma-irradiation and ethylene oxide (EtO)-treatment) and third-body particles, gamma- and EtO-sterilised UHMWPE acetabular cups were tested against CoCrMo femoral heads in a hip joint simulator run for 2.5million cycles in bovine calf serum in the presence of third-body polymethylmethacrylate (PMMA) particles. A method not requiring ultra-centrifugation has been proposed for the isolation of polyethylene wear debris from the serum lubricant. SEM analysis allowed debris shape and morphology to be determined, and the wear mechanism operating in this study to be hypothesised. The morphological features of the wear debris were in agreement with clinical findings, enabling the hip simulator function to be validated. Micro-Raman spectroscopy coupled to PLS analysis showed that the mechanical friction during in vitro tests induced significant crystallinity changes in all the cups. The most significant changes were observed for the EtO-sterilised cups, which showed the highest weight loss.

Presumptive invasive Chrysosporium infection in a bone marrow transplant recipient.

Chrysosporium species caused an invasive infection in an 18-year-old patient following allogeneic sibling bone marrow transplant for T lineage acute lymphoblastic leukemia. This infection began as a facial swelling and extended into the central nervous system. Fungal disease spread rapidly despite antifungal agents. An autopsy showed fungal involvement of brain, lungs, liver and kidneys.

The clinical spectrum of infections with viridans streptococci in bone marrow transplant patients.

A retrospective review of 832 bone marrow transplant patients was performed to determine the clinical spectrum and risk factors for viridans streptococci infections. The incidence of viridans streptococci cultured from the blood and/or cerebrospinal fluid was 15% (123/832), occurring within 15 days of bone marrow transplant in 78% of patients, usually during profound neutropenia. Strep. mitis was the most frequent isolate (47%). Only 27% (33/123) of patients were symptomatic beyond fever, usually with neurologic, pulmonary, and/or cardiovascular manifestations. Ten (8%) of 123 culture positive patients developed a fulminant cardiorespiratory collapse, with a 60% mortality. One additional death occurred due to cerebritis. However, a time dependent covariate analysis found no significant difference in overall mortality (p = 0.30) or duration of hospitalization (p = 0.50) in patients with or without viridans streptococci infections. A multivariate analysis revealed that age less than 18 years (RR = 1.5, p = 0.04) and a primary diagnosis of acute lymphocytic leukemia (RR = 1.5, p = 0.07) were independent and significant risk factors for viridans streptococci infections. Sex, conditioning regimen, donor type, in vitro bone marrow treatment, and acute graft-versus-host disease were not significant. Viridans streptococci should be recognized as pathogens in bone marrow transplant patients which require appropriate antibiotics and aggressive supportive therapy.

Oropharyngeal mucositis complicating bone marrow transplantation: prognostic factors and the effect of chlorhexidine mouth rinse.

Oral mucosal ulceration complicating bone marrow transplantation interferes with patients' comfort, nutrition and may lead to systemic infection derived from the mouth. The mucosal injury results from epithelial damage due to the cytotoxic effects of chemotherapy and radiation conditioning as well as from superficial oropharyngeal infection. Because chlorhexidine gluconate is a broad spectrum topical antimicrobial which has been demonstrably effective in preventing oral infection and gingivitis, we performed a randomized, placebo controlled, double-blind trial of chlorhexidine as a mouth rinse in BMT recipients to study the severity of oral mucositis and both oral and systemic infectious complications. One hundred patients were randomly assigned to receive either chlorhexidine gluconate 0.12% mouth rinse or placebo three times daily from the initiation (day -8) of chemoradiotherapy conditioning until day +35 post-BMT. Chlorhexidine use resulted in a trend toward improved oral hygiene index (reduced dental plaque) (p = 0.06) but did not modify the oral mucositis. Patients using chlorhexidine developed a maximum ulceration of 18 +/- 22% of their oral mucosa, while placebo patients ulcerated 25 +/- 31% of the mouth. Ulcerative mucositis was significantly worse in adults compared with children, in individuals who received methotrexate for graft-versus-host disease prophylaxis, and was most prominent on non-keratinized epithelium. Overall, there was no clinically demonstrable additional therapeutic advantage to the use of chlorhexidine in either reducing the mucositis, controlling oral pain, facilitating oral nutrition, shortening hospital stay, or reducing oral infection with herpes simplex virus. There was a trend toward diminished oral candidiasis in chlorhexidine users (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Group B streptococcal colonization and serotype-specific immunity in pregnant women at delivery.

OBJECTIVE: To describe the relationship between serum concentration of group B streptococcal capsular polysaccharide-specific immunoglobulin (Ig) G, colonization status, race or ethnicity, and age in pregnant women. METHODS: Pregnant women (n = 3307) were enrolled from geographically and ethnically diverse populations. At the time of admission for delivery, swabs of the lower vagina and rectum were obtained for isolation of group B streptococci. In a subset of women whose sera were available, capsular polysaccharide-specific IgG concentrations were quantified by serotype-specific (Ia, Ib, II, III, and V) enzyme-linked immunosorbent assay and compared by group B streptococcal colonization status. RESULTS: Group B streptococcal colonization was detected in 856 women (26%), and the rate was significantly higher among black women (37%) than in other racial or ethnic groups (odds ratio 1.7, 95% confidence interval 1.4, 2.1). Colonization status did not differ by study site or age. Colonization with serotypes Ia, II, III, or V was associated with significantly higher serum concentrations of IgG specific for the capsular polysaccharide of the colonizing serotype compared with noncolonization. However, 48% of colonized women had low capsular polysaccharide-specific IgG levels (less than 0.5 microg/mL) in their delivery sera. Colonized teenagers had the lowest median concentration. CONCLUSION: Colonization with group B streptococcus can elicit a systemic immune response, with a cumulative increase in the prevalence of capsular polysaccharide-specific IgG with increasing age. Conversely, low antibody levels in colonized teenagers might account in part for the reported increased risk of group B streptococcal disease in neonates born to these patients.

The microbiologic aspects, including diagnosis, of beta-hemolytic streptococcal and enterococcal infections.

Basic principles concerning the collection, transport, and processing of clinical specimens for the detection of Streptococcaceae are given. Identification of beta-hemolytic streptococci (S. pyogenes, S. agalactiae, Lancefield group C and G streptococci, S. anginosus) and enterococci is based on the careful observation of colony morphology and hemolytic pattern on sheep blood agar plates; subsequent genus or species confirmation is achieved by rather simple biochemical or enzymatic tests and by detection of streptococcal cell wall carbohydrate antigens (Lancefield grouping). Rapid antigen tests for the detection of group A and B streptococci directly from pharyngeal and vaginal swabs, respectively, are highly specific, thus allowing an immediate antibiotic therapy in patients with a positive test result. The reported sensitivities of these nonculture tests are too low to exclude streptococcal colonization or infection, however. The elucidation of the genetics of some major virulence factors of group A and B streptococci has contributed to knowledge of their association with disease, and molecular techniques have supplemented the traditional (mostly culture and serologic) methods for an improved understanding of the epidemiology and pathogenesis of streptococcal infections. Recently employed examples include the M protein gene typing of group A streptococci by oligonucleotide probes and the use of PCR assays for the detection of the genes encoding for the pyrogenic exotoxins. Restriction enzyme endonuclease digestions of bacterial DNA in association with DNA fragment separation by conventional or PFGE have been applied successfully to several species of Streptococcaceae (e.g., S. pyogenes, S. agalactiae). Enterococci are important pathogens in the hospital setting, exhibiting high morbidity and mortality rates in bacteremic patients with severe underlying disease. Molecular typing methods have clearly confirmed their potential to be nosocomially transmitted. E. faecalis and E. faecium still account for the majority of human infections, but some of the newer enterococcal species (at present 19 species are recognized) have been encountered as well. The definitive species identification of enterococci requires the performance of an array of biochemical tests. The increasing antimicrobial resistance of enterococci, including high-level resistance to penicillins and aminoglycosides and occasionally also to glycopeptides, has hampered standard therapeutic regimens. All enterococci isolated from serious infections should be tested for high-level gentamicin and streptomycin resistance by one of several methods evaluated; beta-lactamase production (primarily found in E. faecalis) is reliably detected by the nitrocefin test.(ABSTRACT TRUNCATED AT 400 WORDS)

Invasive group A streptococcal infections.

Beginning in the mid-1980s and continuing to the present, there has been an apparent increase in the number of severe group A streptococcal infections and their suppurative and nonsuppurative sequelae. The reasons for this epidemiologic change remain incompletely explained. At present, the data seem to suggest that this change is related to the reappearance in the population of not only "new" serotypes, but most likely virulent strains of these serotypes. This has been suggested by available epidemiologic surveys. The pathogenetic mechanism by which these virulent strains cause an increased severity of disease is also incompletely understood. It has been suggested that certain of the streptococcal pyrogenic exotoxins (pyrogenic exotoxin A or B) are associated with strains isolated from severe cases of systemic group A streptococcal infections, but the data conflict in many instances. Clinically, this is an extraordinarily virulent syndrome often leading to the death of the patient within a matter of hours or days. This is despite what would seem to be adequate and appropriate antimicrobial therapy with agents which are effective in vitro against the offending group A streptococcus. Therapy therefore is still based on appropriate antibiotic therapy and support of other systemic manifestations with appropriate medical therapy. At present, prevention of these suppurative and nonsuppurative sequelae is impractical simply because the initial streptococcal infection or colonization is rarely recognized. These events of the last half decade strongly support the need for additional understanding of the epidemiology, pathogenesis, treatment, and prevention of serious group A beta-hemolytic streptococcal infections.