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Background Up to 20% of SA isolates in the United States are penicillin-susceptible (PSSA); however, treatment with penicillin has been discouraged because of concern that routine testing may miss strains that have the capacity to produce clinically significant ß-lactamase in vivo. We performed a retrospective analysis to determine whether PCN therapy for the treatment of PSSA bacteremia was of comparable efficacy and safety to standard therapies. Methods We identified all episodes of SA bacteremia (March 18, 2010–July 23, 2018). SA penicillin susceptibility testing in our lab was performed by broth microdilution followed by nitrocefin ß-lactamase testing per CLSI guidelines on these isolates. A retrospective chart review was performed and our primary outcome was a composite endpoint of clinical success (no change in PSSA therapy due to persistent or worsening signs and symptoms, no PSSA bacteremia recurrence or persistence, and no infection‐related mortality). Microbiologic failure was defined as either failure to clear bacteremia/infection or recurrence after completion of therapy. Patients were followed until last contact with our medical system, the only tertiary center in the region. We compared our rates of success, mortality, and adverse drug reaction to historical SA bacteremia controls from the literature. Results PSSA accounted for 13% (130/971) of SA bloodstream episodes. Nineteen patients with PSSA (15%) were treated with PCN and 79% (15/19) achieved the primary endpoint of clinical success. Of the 4 patients who did not achieve the endpoint, 2 developed rash and were switched to a different antibiotic and 2 died from complications of sepsis. One of the patients died after clearing blood cultures but had DIC and a catastrophic intracranial hemorrhage, the other died of overwhelming sepsis after 4 days (2 days nafcillin, 2 days PCN) with continued bacteremia. Thus, our only microbiologic failure was due to early death from sepsis. Rates of success, mortality and drug reaction were similar to prior reports of alternative standard therapies (Table 1). Conclusion PCN is a viable treatment option for PSSA bacteremia as identified by routine laboratory testing. Further study will include characterizing the presence of ß-lactamase in these patient’s isolates. Disclosures All authors: No reported disclosures.

Noninvasive vaginal infections by Staphylococcus aureus strains producing the superantigen TSST-1 can cause menstrual toxic shock syndrome (mTSS). With the objective of exploring the basis for differential susceptibility to mTSS, the relative responsiveness to TSST-1 of healthy women has been investigated. Peripheral blood mononuclear cells from healthy donors were incubated with purified TSST-1 or with the T-cell mitogen phytohemmaglutinin (PHA), and proliferation was measured. The concentrations of TSST-1 and PHA required to elicit a response equivalent to 15% of the maximal achievable response (EC15) were determined. Although with PHA, EC15 values were comparable between donors, subjects could be classified as being of high, medium, or low sensitivity based on responsiveness to TSST-1. Sensitivity to TSST-1-induced proliferation was associated with increased production of the cytokines interleukin-2 and interferon-γ. When the entire T lymphocyte population was considered, there were no differences between sensitivity groups with respect to the frequency of cells known to be responsive to TSST-1 (those bearing CD3(+) Vβ2(+)). However, there was an association between sensitivity to TSST-1 and certain HLA-class II haplotypes. Thus, the frequencies of DR7DQ2, DR14DQ5, DR4DQ8, and DR8DQ4 haplotypes were greater among those with high sensitivity, a finding confirmed by analysis of responses to immortalized homozygous B cell lines. Collectively, the results reveal that factors other than neutralizing antibody and the frequency of Vβ2(+) T lymphocytes determine immunological responsiveness to TSST-1. Differential responsiveness of lymphocytes to TSST-1 may form the basis of interindividual variations in susceptibility to mTSS.

Many cases of neonatal toxic shock syndrome (TSS)-like exanthematous disease but few cases of menstrual TSS (mTSS) have been reported in Japan. We determined the prevalence of mucosal colonization with Staphylococcus aureus and of positive antibodies to TSS toxin 1 (TSST-1) among 209 healthy Japanese women in Tokyo. S. aureus isolates from mucosal sites were characterized with respect to TSST-1 production and resistance genotype. Antibody titers were determined for test subjects and for 133 Japanese and 137 Caucasian control women living in the United States. S. aureus was isolated from at least one site in 108 of 209 women (52%) in Tokyo. Of the 159 S. aureus isolates recovered, 14 (9%) were TSST-1 positive (12 unique strains). Twelve of 209 women (6%) were colonized with a TSST-1-producing strain; two (S. aureus were comparable in Japan and the United States, despite low seropositivity to TSST-1 in Japan. Environmental factors appear to be important in promoting the development of anti-TSST-1 antibodies, as there was a significant difference in titers between Japanese women living in Tokyo and those living in the United States. Most colonizing TSST-1-producing S. aureus strains in Japan were genotypically similar to mTSS strains found in the United States.

Menstrual toxic shock syndrome (mTSS) is thought to be associated with colonization with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus in women with insufficient antibody titers. mTSS has been associated with menstruation and tampon use, and although it is rare, the effects can be life threatening. It remains of interest because of the widespread use of tampons, reported to be about 70% of women in the United States, Canada, and much of Western Europe. This comprehensive study was designed to determine S. aureus colonization and TSST-1 serum antibody titers in 3,012 menstruating women in North America between the ages of 13 and 40, particularly among age and racial groups that could not be assessed reliably in previous small studies. One out of every four subjects was found to be colonized with S. aureus in at least one of three body sites (nose, vagina, or anus), with approximately 9% colonized vaginally. Eighty-five percent of subjects had antibody titers (≥1:32) to TSST-1, and the vast majority (81%) of teenaged subjects (13 to 18 years) had already developed antibody titers. Among carriers of toxigenic S. aureus , a significantly lower percentage of black women than of white or Hispanic women were found to have antibody titers (≥1:32) to TSST-1 (89% versus 98% and 100%). These findings demonstrate that the majority of teenagers have antibody titers (≥1:32) to TSST-1 and are presumed to be protected from mTSS. These findings also suggest that black women may be more susceptible to mTSS than previously thought.

We report 3 cases of recurrent nonmenstrual toxic shock syndrome (TSS) and review the clinical manifestations, diagnosis, and treatment. The primary sites of infection were the genital tract (in a patient who underwent cesarean delivery), the upper respiratory tract, and a breast abscess. In all 3 patients, the initial illness was not recognized to be TSS; only after development of recurrent illness with desquamation was this diagnosis entertained. Strains of Staphylococcus aureus that were isolated from 2 patients produced TSS toxin-1, whereas the third strain produced staphylococcal enterotoxin B. All 3 patients lacked antibody to the implicated toxins at the time of presentation with recurrent illness. Nonmenstrual TSS can occur in a variety of clinical settings and may be recurrent. The presence of desquamation during a febrile, multisystem illness could suggest this diagnosis and should prompt the clinician to obtain appropriate cultures for S. aureus.

We report a skin and soft-tissue infection outbreak among football team members due to a USA300 methicillin-susceptible Staphylococcus aureus (MRSA) strain with genes coding for Panton-Valentine leukocidin and the arginine catabolic mobile element. We postulate that the strain is a community-associated USA300 MRSA strain that lost methicillin resistance but retained important virulence factors.

To determine whether tampons composed of cotton or rayon differ in their effects on production of TSST-1 in vitro, two methods of bacterial cultivation, with and without agitation, were used to study the effects of 16 commercially available and experimental tampons on production of TSST-1. Experiments were done in blinded fashion. TSST-1 was produced in medium alone in the absence of a tampon by both methods. Neither cotton nor rayon tampons consistently increased toxin production, nor were there significant differences between them in their effects on TSST-1. In contrast, a tampon composed of carboxymethylcellulose and polyester foam increased production of TSST-1 to a large degree in both culture systems. Thus, neither cotton nor rayon amplifies production of TSST-1 in vitro, and cotton tampons cannot be claimed to be inherently safer on the basis of such data.

Background Menstrual Toxic Shock Syndrome (mTSS) is thought to be associated with the vaginal colonization with specific strains of Staphylococcus aureus TSST-1 in women who lack sufficient antibody titers to this toxin. There are no published studies that examine the seroconversion in women with various colonization patterns of this organism. Thus, the aim of this study was to evaluate the persistence of Staphylococcus aureus colonization at three body sites (vagina, nares, and anus) and serum antibody to toxic shock syndrome toxin-producing Staphylococcus aureus among a small group of healthy, menstruating women evaluated previously in a larger study. Methods One year after the completion of that study, 311 subjects were recalled into 5 groups. Four samples were obtained from each participant at several visits over an additional 6-11 month period: 1) an anterior nares swab; 2) an anal swab; 3) a vagina swab; and 4) a blood sample. Gram stain, a catalase test, and a rapid S. aureus-specific latex agglutination test were performed to phenotypically identify S. aureus from sample swabs. A competitive ELISA was used to quantify TSST-1 production. Human TSST-1 IgG antibodies were determined from the blood samples using a sandwich ELISA method. Results We found only 41% of toxigenic S. aureus and 35.5% of non-toxigenic nasal carriage could be classified as persistent. None of the toxigenic S. aureus vaginal or anal carriage could be classified as persistent. Despite the low persistence of S. aureus colonization, subjects colonized with a toxigenic strain were found to display distributions of antibody titers skewed toward higher titers than other subjects. Seven percent (5/75) of subjects became seropositive during recall, but none experienced toxic shock syndrome-like symptoms. Conclusions Nasal carriage of S. aureus appears to be persistent and the best predicator of subsequent colonization, whereas vaginal and anal carriage appear to be more transient. From these findings, it appears that antibody titers in women found to be colonized with toxigenic S. aureus remained skewed toward higher titers whether or not the colonies were found to be persistent or transient in nature. This suggests that colonization at some point in time is sufficient to elevate antibody titer levels and those levels appear to be persistent. Results also indicate that women can become seropositive without experiencing signs or symptoms of toxic shock syndrome.

Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed.We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy.Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, -10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004).Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].).

Menstrual toxic shock syndrome (mTSS) is an acute febrile disease accompanied by hypotension and multiple organ involvement. Infection with Staphylococcus aureus producing the superantigen toxic shock syndrome toxin-1 (TSST-1) vaginally is necessary; however, only a small fraction of those infected with TSST-1 producing bacteria actually develop mTSS, suggesting that host factors modulate disease susceptibility. Serum antibodies to the toxin protect against development of the syndrome, but not all antibodies can neutralize the toxin. We set out to determine whether risk of developing the syndrome is related to the absence of neutralizing antibody and if antibody isotypes influence the neutralization capacity. In healthy subjects, TSST-1-binding serum antibodies were exclusively of the IgG and IgM classes; however, toxin-neutralizing capacity was correlated to the TSST-1-specific IgG1 and IgG4 antibodies (r 2=0.88, p

Nonmenstrual toxic shock syndrome (TSS) in adults has been associated with various staphylococcal respiratory tract infections, including pharyngitis, tonsillitis, pneumonia, and postinfluenza respiratory tract infections. In children, nonmenstrual TSS has also been described as a complication of bacterial tracheitis. We describe the case of a 40-year-old woman who presented with laryngotracheitis as well as clinical and laboratory evidence of TSS. Culture of her sputum samples yielded pure growth of Staphylococcus aureus, which was shown to produce TSS toxin 1 (TSST-1). The patient responded promptly to therapy with iv clindamycin. We discuss the association of TSS with staphylococcal laryngotracheitis and the role of clindamycin in the treatment of TSS. To our knowledge, there are no previous reports of TSS complicating laryngotracheitis in adults.

We performed a series of collaborative experiments to clarify the effect of Mg++ on production of toxic-shock-syndrome toxin-1 (TSST-1) in various culture media. TSST-1 production was enhanced by adding ethylenediamine-tetraacetic acid (EDTA) at appropriate concentrations to brain-heart infusion and beef-heart medium. The magnitude of this effect depended both on the number of bacteria used to inoculate the media and on the sampling time. Large inocula prepared in media containing high levels of Mg++ introduced sufficient Mg++ to the growth medium to influence subsequent bacterial multiplication and toxin production. Small inocula of bacteria washed in Mg++-deficient medium before inoculation did not, however, multiply or produce toxin in Mg++-deficient medium. Maximal toxin expression occurred during late logarithmic phase, regardless of Mg++ concentration, and Mg++ appeared to control when late logarithmic stage of growth would be achieved. The toxin-enhancing effect of EDTA was reversed by adding excess Mg++ to treated medium.

We studied the induction of human interleukin-1 (IL-1) production in strains of Staphylococcus aureus isolated from patients with nonmenstrual toxic shock syndrome (TSS). Of the 20 TSS-associated strains studied, 11 produced and nine did not produce TSS toxin-1 (TSST-1). Human monocytes were incubated with dilute staphylococcal supernatants, and IL-1 production was measured in a lymphocyte-activating factor assay. All 20 TSS-associated strains were potent inducers of IL-1, in comparison with none of 10 vaginal isolates of S. aureus from healthy women. TSST-1-positive strains were more potent than TSST-1-negative strains. Nine TSST-1-negative TSS-associated strains were compared with 14 strains of S. aureus from other clinical settings and were found to be significantly more potent inducers of IL-1 (P less than .01). Eight of these nine TSS-associated strains produced at least one staphylococcal enterotoxin. Stimulation of monocytes by products of S. aureus may play a role in the pathogenesis of TSS.

Strains of Staphylococcus aureus isolated from patients with toxic shock syndrome (TSS) make a characteristic protein known as toxic-shock-syndrome toxin-1 (TSST-1), but the role of this protein in the pathogenesis of TSS is not certain. We have purified TSST-1 by using a combination of alcohol precipitation, isoelectric focusing, and gel chromatography. TSST-1 has an isoelectric point of 7.2 and a molecular weight of 23,100, in accordance with previously published determinations for this protein, and is serologically identical to pyrogenic exotoxin C and staphylococcal enterotoxin F. In highly purified form, TSST-1 is a potent inducer of interleukin-1 production by human monocytes, as quantitated in a thymocyte-proliferation assay. This capability is not attributable to contamination by other staphylococcal products or gram-negative endotoxin and can be blocked by hydrocortisone. Many features of TSS suggest that induction of interleukin-1 by TSST-1 in vivo may play a central role in the elaboration of this disease.

A typographical error appeared in "The Relative Role of Bacterial Cell Wall and Capsule in the Induction of Inflammation in Pneumococcal Meningitis" by Elaine Tuomanen et al. (March 1985). The second sentence of the legend for figure 3 on page 538 is incomplete and should appear as follows: . . . concentrations present on 106 cells (hatched bars with stipple, cell wall; cross-hatched bars, capsule), or alternatively at 2 mg/0.2 ml (stippled bars, cell wall; hatched bars, capsule)."

Ces variables exercent leur effet maximal lorsque la concentration de Mg du milieu de culture est limitant et inversement, lorsque du Mg ++ est present en exces, la production de toxine est diminuee, quelle que soit l'action des autres variables

Understanding of the pathogenesis of toxic shock syndrome (TSS) has come from the juxtaposition of epidemiologic, clinical, immunologic, and physiologic studies. A hypothesis has been developed for the pathogenesis of menstrually related TSS. Certain tampon fibers that are highly absorbent for water are also ion exchangers for magnesium ions. The latter ions uniquely affect the production of TSS toxin 1 (TSST-1) by appropriate strains of Staphylococcus aureus, with a marked increase in the amount of toxin when magnesium concentrations are limiting and suppression of toxin production when magnesium is in excess. Many epidemiologic features of TSS could be explained by this hypothesis. The absorbability of highly absorptive fibers is not affected by the addition of small amounts of magnesium sufficient to suppress production of TSST-1; thus absorption is distinguishable from toxin production in vitro. TSST-1 stimulates production of interleukin 1 and of tumor necrosis factor and is highly toxic when absorbed slowly. Like TSST-1, staphylococcal enterotoxins are lethal to rabbits when given by slow injection, and some enterotoxins may be more lethal than TSST-1.

We studied the effect of toxic-shock-syndrome toxin-1 (TSST-1) on production of tumor necrosis factor (TNF) by human monocytes. Adherent mononuclear cells were stimulated with TSST-1 and their supernatants assayed for TNF by using L929 cells in a cytotoxicity assay. TSST-1 stimulated production of TNF over a wide range of concentrations. The cytotoxicity of monocyte supernatants was neutralized by antibody to TNF but not by antibody to interleukin-1 or by normal rabbit serum. TSST-1 and lipopolysaccharide (LPS) had a synergistic effect on monokine production. Monocytes "primed" with TSST-1 produced more interleukin-1 and TNF in response to LPS than did unprimed cells. Treating monocytes with LPS before TSST-1 and co-incubating the two agents with cells for 24 h also enhanced monokine production under some circumstances. These studies suggest a role for TNF in the pathogenesis of toxic shock syndrome, as a consequence of induction by TSST-1 alone or the synergistic effects of several bacterial products.

Since toxic shock syndrome (TSS) was formally defined in 1978, much has been learned about the clinical and epidemiologic features of this disease. Furthermore, a specific staphylococcal protein, known as toxic shock syndrome toxin 1 (TSST-1), has been identified as a putative pathogenic agent. Conditions affecting production of TSST-1 have been discussed during other sessions of this symposium. It is evident, however, that toxins other than TSST-1 must be capable of causing TSS, since not all TSS-associated strains of Staphylococcus aureus produce TSST-1. This issue has also been addressed in detail elsewhere. In this overview, I will focus on mechanisms, proposed and documented, by which the TSS toxins cause disease. As indicated in table 1, TSS may be the consequence of the pathogenic effects of several staphylococcal products acting alone or in concert. Moreover, other microbial products, particularly endotoxin of gram-negative bacilli, have been cited as possible contributors to the pathogenic process. These agents may act either by directly exerting toxic effects on host tissues or by inducing the production and release of a variety of endogenous mediators, which in turn combine to sculpt this complex syndrome. Endogenous mediators likely to be involved (on the basis either of investigations performed to date with TSST-1 or of known activities under other circumstances) are also listed in table 1.

We developed a competitive, enzyme-linked immunosorbent assay for the quantitation of toxic shock syndrome toxin 1 (TSST-1). Polyvalent immunoglobulin G from immunized rabbits was used as the capture antibody, and alkaline phosphatase conjugated to purified toxin served as the indicator enzyme. A standard curve was generated with each experiment, from which the concentration of toxin in culture supernatants was extrapolated. The assay was useful for determining toxin concentrations of 0.03 to 0.5 micrograms/ml, which is a substantial, practical improvement over immunodiffusion methods. Staphylococcal enterotoxins A through E were not significantly cross-reactive in the assay, and staphylococcal protein A did not interfere with quantitation of TSST-1. By testing a variety of staphylococcal strains, we found 100% concordance between toxin determinations made with our assay and those made by the investigators from whom the strains were obtained. The competitive, enzyme-linked immunosorbent assay is a highly reproducible, inexpensive means of determining TSST-1 concentrations and may have broad applicability in the field of toxic shock research.