Clostridium sordellii infections pose difficult clinical challenges and are usually fatal. Most commonly, these infections occur after trauma, childbirth, and routine gynecological procedures, but they have recently been associated with medically induced abortions and injection drug use. We report 2 fatal cases, one of which was associated with minor trauma, and the other of which was associated with normal childbirth, and we summarize the clinical features of 43 additional cases of reported C. sordellii infection. Of these 45 cases, 8 (18%) were associated with normal childbirth, 5 (11%) were associated with medically induced abortion, and 2 (0.4%) were associated with spontaneous abortion. The case-fatality rate was 100% in these groups. Ten (22%) of the C. sordellii infections occurred in injection drug users, and 50% of these patients died. Other cases of C. sordellii infection (in 19 patients [43%]) occurred after trauma or surgery, mostly in healthy persons, and 53% these patients died. Overall, the mortality rate was 69% (31 of 45 patients). Eighty-five percent of all patients with fatal cases died within 2-6 days of initial infection, and nearly 80% of fatal cases developed leukemoid reactions. Rapid diagnostic tests and improved treatments are needed to reduced the morbidity and mortality associated with this devastating infection.

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Severe, invasive group A streptococcal infections have reemerged worldwide, and extracellular toxins, including streptococcal pyrogenic exotoxin B (SpeB), have been implicated in pathogenesis. The genetic regulation of SpeB is not fully understood, and the mechanisms involved in the processing of the protoxin to its enzymatically active form have not been definitively established. The present work demonstrated that the genes encoding SpeB (speB) and a peptidyl-prolyl isomerase (prsA) constitute an operon with transcription initiated from two promoters upstream of speB. Further, the speB-prsA operon was transcribed as a bicistronic mRNA. This finding is in contrast to the generally accepted notion that speB is transcribed only as a monocistronic gene. In addition, prsA has its own promoter, and transcription from this promoter starts in early log phase, prior to the transcription of speB. Genomic disruption of prsA decreased the production of enzymatically active SpeB but not the level of the pro-SpeB zymogen. Taken together, these results demonstrate that prsA is required for production of fully mature, enzymatically active SpeB.Group A streptococcus (GAS) causes many diseases in humans, ranging in severity from milder infections such as pharyngitis, simple cellulitis, erysipelas, and scarlet fever to life-threatening necrotizing fasciitis, septicemia, and toxic shock syndrome. One of the many potentially important virulent factors produced by this organism is streptococcal pyrogenic exotoxin B (SpeB). As a potent cysteine proteinase, SpeB cleaves multiple streptococcal virulence factors, including M protein (3), as well as many host factors controlling inflammation (18,20).The gene for SpeB (speB) is chromosomally located on every GAS strain studied and consists of a 1,196-base pair (bp) open reading frame yielding a 371-amino-acid polypeptide with a predicted molecular weight of 40,000 (16). SpeB is secreted strictly in the late log/early stationary phase of growth as a proteinase precursor that must be proteolytically cleaved to the mature active form having a calculated molecular mass of approximately 28 kDa. SpeB is also found on the surfaces of the bacteria and possesses glycoprotein and laminin binding activities (19). While all strains of GAS are endowed with the gene for SpeB, not all strains produce the toxin in vitro, and even among strains that do, the quantity produced varies greatly from strain to strain (6,15,16,22,31). Other environmental factors, such as acidic pH, concentration of NaCl, the availability of nutrients, the presence of kanamycin, etc., also affect speB expression (7, 9, 39).Current knowledge regarding SpeB's transcriptional regulation and maturation is derived from many labs around the world. At the transcriptional level, rgg (also known as ropB) positively regulates SpeB expression and production (5), as does the global regulator mga (35). In addition, inactivation of both oligopeptide and dipeptide transport systems diminished speB mRNA levels (33, 34). At the posttranscriptiona...

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In summary, these findings suggest that the treatment of CDI patients with tigecycline could effectively both control disease progression and limit its spread by disrupting sporulation.

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Hypervirulent BI/NAP1/027 strains of Clostridium difficile have been associated with increased mortality of C. difficile infection (CDI). The emergence of highly fluoroquinolone (FLQ)-resistant BI/NAP1/027 strains suggests that FLQ exposure may be a risk factor for CDI development. However, the mechanism for this is not clear. We compared the effects of subinhibitory concentrations of ciprofloxacin on Toxin A and B gene expression and protein production in recent (strain 039) and historical (strain 5325) BI/NAP1/027 clinical isolates with high-and low-level ciprofloxacin resistance, respectively. In the highly ciprofloxacin-resistant isolate (strain 039), ciprofloxacin significantly and dose-dependently increased Toxin A gene expression and shifted its expression to earlier in its growth cycle; TcdB gene expression also increased but was less sensitive to low-dose ciprofloxacin. Maximal Toxin A/B production (4 ng ml "1 ) was increased twofold and occurred significantly earlier than in the untreated control. In strain 5325, ciprofloxacin at 0.25¾MIC markedly increased both tcdA and tcdB expression but their temporal dynamics were unchanged. Maximal toxin production (250 ng ml "1 ) was reduced approximately threefold compared with that of the untreated control. These results demonstrate significant differences in ciprofloxacin-induced toxin gene expression and protein production among BI/ NAP1/027 isolates, and offer a new paradigm for FLQ-associated CDI caused by recent, highly antibiotic-resistant strains.

Purpose of review This review summarizes clinical and basic science evidence linking trauma and nonsteroidal anti-inflammatory drug (NSAID) use to initiation and progression of severe group A streptococcal (GAS) soft tissue infection. Recent findings New evidence includes recent clinical series and controlled studies that lend support to an NSAID/GAS association, basic science studies that demonstrate unique roles for nonpenetrating injury and NSAID administration in initiation of cryptogenic GAS infection and experimental studies showing that nonselective NSAIDs accelerate disease progression and limit antibiotic efficacy in established GAS soft tissue infections. Potential mechanisms for these processes are discussed. Summary NSAIDs are important anti-inflammatory and analgesic drugs; however, new experimental data suggest that nonselective NSAIDs do more than simply mask the signs and symptoms of developing GAS infection. A more thorough understanding of the triadic interplay of injury-triggered immune signaling, GAS soft tissue infection and NSAIDs is of significant clinical importance and could shift the current paradigm of pain management to avert the consequences of such devastating infections.