Association of phenotypic and genotypic characteristics of invasive Streptococcus pyogenes isolates with clinical components of streptococcal toxic shock syndrome.

Sixty-two invasive Streptococcus pyogenes strains, including 32 strains isolated from patients with streptococcal toxic shock syndrome (STSS), were analyzed for the following phenotypic and genotypic characteristics: M-protein type, serum opacity factor production, protease production, the presence of streptococcal pyrogenic exotoxin (Spe) genes A, B, and C, and in vitro production of SpeA and SpeB. These characteristics were analyzed for possible associations with each other as well as with clinical components of STSS. M-type 1, the most commonly isolated M-type, was significantly associated with protease production. Protease activity was significantly associated with the clinical sign of soft tissue necrosis. M-type 1 and 3 strains from STSS patients were significantly associated with the clinical signs of shock and organ involvement as well as with SpeA production in vitro. Finally, the production of SpeA was significantly associated with the clinical component of shock and organ involvement as well as with rash. These data suggest that STSS does not make up a single syndrome but, rather, that the multiple STSS clinical criteria probably reflect different phenotypic characteristics of individual S. pyogenes isolates.

Innovative index system for reporting microbiology laboratory results.

A new computerized format for presenting microbiology laboratory results has been designed and evaluated. This new system uses an index format providing a concise summary of the status of each test ordered and the results for each test organized by the source of the specimen on the first page of the report. This is followed by complete, detailed microbiology results sorted in reverse chronological order. This new system was significantly (P < 0.05) faster and easier to use than a standard source-category reporting system used in many hospitals. In addition, the index format was overwhelmingly preferred by the individuals evaluating both systems.

Biochemical models as early predictors of the etiology of acute pancreatitis.

In this study we observed the discriminative ability of five commonly measured laboratory tests to distinguish between gallstone- and non-gallstone-associated pancreatitis. We also assessed the ability of the lipase-amylase ratio to discriminate between alcohol- and non-alcohol-induced pancreatitis. One hundred sixty-two patients with acute pancreatitis were included in the study. Group A consisted of patients presenting to our hospital in 1988 and 1989. Group B consisted of patients presenting in 1992. Models developed using group A patients were validated using group B patients. For gallstone pancreatitis, AST (threshold value 80 IU/liter) alone and a three-factor model, AST, ALP and bilirubin (threshold values of 80 IU/liter, 115 IU/liter, and 15 mumol/liter, respectively) were the best predictors, correctly classifying at least 80% of cases in group A and B. A lipase-amylase ratio of two correctly classified only 48% of cases in group A and 54% in group B. We conclude that biochemical models are useful in predicting the presence of gallstone pancreatitis but not alcoholic pancreatitis.

Outbreak of group A streptococcus septicemia in children. Clinical, epidemiologic, and microbiological correlates.

OBJECTIVE: To determine the epidemiologic, clinical, and microbiological features of group A streptococcus septicemia in children. DESIGN: A descriptive series of 34 cases over an 11-year period from 1980 through 1990. SETTING: An academically affiliated tertiary-care pediatric hospital, the principal referral center for the state of Colorado and surrounding states. PARTICIPANTS: Thirty-four patients with positive blood cultures for group A streptococcus (33 medical records were available). MAIN OUTCOME MEASURES: Yearly incidence and clinical features of cases; microbiological features of isolated organisms. RESULTS: There was a significant increase (P = .01) in the incidence of group A streptococcus bacteremia over an 11-year period, with 14 (41%) of these cases occurring in 1989 and 1990. Patients had a rapidly progressing illness, usually without preceding pharyngitis. The prominent M and T types were 1 (4) and 12 (4). Eleven (73%) of the 15 strains produced pyrogenic exotoxin B that significantly correlated with production of proteinase. CONCLUSION: There appears to be an increase in group A streptococcus bacteremia in children that is associated with a strain phenotype that suggests a change in organism virulence.

Phospholipase C activity in microorganisms associated with reproductive tract infection.

Phospholipase C (lecithinase or phosphatidylcholine phosphorylase) catalyzes the hydrolysis of lecithin into phosphorylcholine and 1,2-diglyceride. Bacterial production of phospholipase C may damage reproductive tract tissues by both direct and indirect mechanisms. Use of the synthetic substrate p-nitrophenylphosphorylcholine phospholipase C activity was determined in 204 isolates representative of those found in female genital tract. Multiple aerobic (28%) and anaerobic (28%) reproductive tract microorganisms showed phospholipase C activity. Phospholipase C-producing isolates included strains of Bacteroides fragilis, B. bivius, B. thetaiotaomicron, Gardnerella vaginalis, and group B streptococcus. Phospholipase C activity was heterogenous; not all isolates that belong to a particular species showed activity. Phospholipase C production may be a possible virulence factor produced by a number of microflora commonly implicated in various reproductive tract infections or conditions, as well as in some instances of preterm birth.

Antenatal microbiologic and maternal risk factors associated with prematurity.

In a prospective study of 202 women (gestational age 24 +/- 4 weeks), we evaluated possible influences of lower genital tract infection or bacterial conditions on obstetric outcomes, including preterm labor, preterm premature rupture of membranes, and preterm birth. The presence of bacterial vaginosis (18.7%) was associated with an increased risk of preterm labor (relative risk, 2.6; 95% confidence interval, 1.08 to 6.46). For women with bacterial vaginosis who also had Mobiluncus species morphotypes identified on Gram stain, the relative risk of preterm labor was 3.8 (95% confidence interval, 1.32 to 11.5). Presence of vaginal Mycoplasma hominis (10.8% of patients) was associated with both preterm labor (relative risk, 1.8; 95% confidence interval, 0.77 to 4.4) and preterm birth (relative risk, 5.1; 95% confidence interval, 1.45 to 17.9). Recovery of Staphylococcus aureus (3.0%) was associated with preterm labor (relative risk, 3.1; 95% confidence interval 1.12 to 8.7). Identification of two or more bacterial-linked abnormalities was also associated with preterm labor (relative risk, 3.3; 95% confidence interval, 1.44 to 7.58). An increased level of vaginal wash protease (greater than or equal to 10 trypsin units) (16%) was associated with preterm labor and was noted in 50% of women with preterm premature rupture of membranes. A history of prior preterm birth was the single best historical predictor of both preterm labor (relative risk, 3.6; 95% confidence interval, 1.92 to 6.83) and preterm birth (relative risk, 6.7; 95% confidence interval, 2.2 to 20.4). History of three or more abortions, antenatal urinary tract infection, and occurrence of medical complications during pregnancy also correlated with increased risk of preterm labor. These findings affirm and refine associations of various maternal reproductive tract infections with preterm labor, premature rupture of membranes, and birth, allowing for controlled treatment trials aimed at prevention of preterm birth.

Selective expansion of T cells expressing V beta 2 in toxic shock syndrome.

Infection with Staphylococcus aureus and the production of toxic shock syndrome toxin-1 (TSST-1) have been implicated in the pathogenesis of toxic shock syndrome. Previous in vitro studies have demonstrated that TSST-1 is a powerful but selective stimulator of human T cells, and that the majority of activated cells express the TCR V beta 2 gene segment. We therefore studied patients with toxic shock syndrome using a modification of the PCR to determine if expansion of V beta 2+ T cells is a marker of the in vivo disease process. Five of eight patients studied demonstrated markedly elevated levels of circulating V beta 2+ T cells, whereas none showed significantly elevated levels of T cells expressing other V beta gene segments. The results suggest that toxin-mediated T cell activation, which involves a large fraction of the human T cell repertoire, may be critical in the pathogenesis of this disease.

Therapy of toxic shock syndrome.

Toxic shock syndrome (TSS) is an acute febrile, exanthematous illness associated with multisystem failure including shock, renal failure, myocardial failure and adult respiratory distress syndrome (ARDS). It usually presents with fever, pharyngitis, diarrhoea, vomiting, myalgia, and a scarlet fever-like rash, and may progress rapidly (within hours) to signs of hypovolaemic hypotension such as orthostatic dizziness or fainting. The signs and symptoms of toxic shock syndrome should be recognised early to permit successful therapy. Patients are usually suffering from hypovolaemia due to leaky capillaries and fluid loss into the interstitial space, and consequently large volumes of fluid, both crystalloid (e.g. saline, electrolyte-solutions) and colloid (e.g. albumin, intravenous gamma-globulin), may be necessary to maintain adequate venous return and cardiac output. Patients with toxic shock syndrome usually have a focus of staphylococcal infection such as a surgical wound infection or soft tissue abscess, or they may have TSS associated with menstruation and use of a vaginal device such as tampons. The site of infection should be adequately drained and treated with antimicrobial therapy. Subacute complications including ARDS and myocardial failure require a thorough understanding of the underlying pathophysiology to ensure appropriate treatment. Recurrences of TSS can be avoided by appropriate antimicrobial treatment and avoidance of recurrent conditions which might favour staphylococcal toxin production (e.g. use of tampons during menstruation). More than 95% of patients survive toxic shock syndrome if appropriate therapy is instituted early.

Toxic shock syndrome associated with Staphylococcus aureus sinusitis in children.

Toxic shock syndrome (TSS) is a severe, acute, multisystem illness associated with rash and shock. It is usually associated with a focal infection (e.g., during menstruation associated with tampon use, abscess, surgical wound infection) caused by certain Staphylococcus aureus strains. Identification and drainage of the focus of infection may be important in therapy. Occasionally, a focus of infection is not obvious, requiring additional diagnostic procedures. Three cases of children with TSS associated with sinusitis and no other focus of S. aureus infection are presented, demonstrating the important consideration of the perinasal sinuses as a cryptic focus of S. aureus infection causing TSS.

Maternal deaths associated with Clostridium sordellii infection.

Clostridium sordellii is a common soil and enteric bacterium that is infrequently recovered from the vagina. We describe three women in which C. sordellii caused puerperal infection and a distinctive and lethal toxic shock-like syndrome. Patients were less than 1 week post partum and each had a single, limited focus of infection including infection associated with a retained vaginal sponge, a cesarean section operative site, and endometritis. Each patient had a distinctive course characterized by sudden onset of clinical shock marked by severe and unrelenting hypotension associated with marked, generalized tissue edema and "third spacing" with increased hematocrit, presence of marked leukemoid reaction with total neutrophil counts of 84,000/mm3, 66,000/mm3, and 93,600/mm3, absence of rash or fever, limited or no myonecrosis, and a rapid and uniformly lethal course. Hypoalbuminemia was also noted. Similar findings were noted in prior isolated reports of C. sordellii-mediated postpartum or surgical infection. Treatment of animals with C. sordellii or closely related C. difficile toxins produces similar findings. We suggest that localized infection with toxin-producing strains of C. sordellii can produce a rapidly lethal toxic shock-like syndrome. Further study and earlier recognition of this syndrome may be life-saving in other patients.

Clinical identification and comparative prognosis of high-risk patients with Haemophilus influenzae meningitis.

One hundred ninety-five consecutive children with Haemophilus influenzae meningitis were retrospectively reviewed to identify those patients at high risk of death or severe sequelae using a previously described clinical scoring system. One hundred sixty-nine children (86.7%) had prognostic scores less than or equal to 4.0 and all survived. Twenty-six patients (13.3%) had prognostic scores greater than or equal to 4.5 points. Five of these high-risk patients (2.6% overall) died as a direct result of their acute meningitis. Of the remaining 21 survivors, 15 were available for prospective, observer-blinded, follow-up evaluation, as compared with 15 low-risk control patients matched for age, sex, and year of admission. High-risk patients were significantly more likely to have more serious sequelae (2.0 +/- 2.1) as compared with low-risk controls (0.5 +/- 0.7). Those high-risk patients who by the choice of their treating physicians had received corticosteroids (and usually osmotic therapy as well) appeared to have outcomes similar to their matched low-risk controls and significantly better than those high-risk patients who did not receive such additional therapy.

Alteration of proteins reacting with antibody to toxic shock syndrome toxin 1 by endogenous proteases of Staphylococcus aureus.

Many cases of toxic shock syndrome (TSS) have been associated with Staphylococcus aureus strains that produce in vitro a 22,000-dalton protein called toxic shock syndrome toxin 1 (TSST-1). TSST-1 has been shown to be linked phenotypically to the production of the type II (thiol) staphylococcal protease; however, some strains clearly associated with TSS do not produce TSST-1. With the use of a variety of antibodies to TSST-1, representatives of both TSST-1-positive and TSST-1-negative TSS-associated strains were shown to produce proteins of 32,000, 53,000, and 76,000 daltons that cross-reacted with TSST-1 but that did not appear to be TSST-1 aggregates or to be protein A. TSST-1-negative strains were significantly (P less than .05) more likely than TSST-1-producing strains to produce the type I protease and less likely to produce the type II protease. In vitro the type I (serine) protease digests purified TSST-1. When combinations of type II and type III protease chemical inhibitors were used, the production of the high-molecular-weight cross-reacting proteins during in vitro growth could be selectively enhanced. Since the infected foci (e.g., abscess, vagina) associated with TSS may contain natural protease inhibitors, it is possible that such TSST-1 cross-reacting proteins may be expressed in vivo or that levels of TSST-1 may be increased by an inhibitor of the serine protease.