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D E Low

Publications and source records attributed to D E Low.

At least 73 records · Page 4Linked to original sources
PubMed2000

Inverse relation between disease severity and expression of the streptococcal cysteine protease, SpeB, among clonal M1T1 isolates recovered from invasive group A streptococcal infection cases.

The streptococcal cysteine protease (SpeB) is one of the major virulence factors produced by group A streptococci (GAS). In this study we investigated if differences exist in SpeB production by clonally related M1T1 clinical isolates derived from patients with invasive infections. Twenty-nine of these isolates were from nonsevere cases and 48 were from severe cases, including streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) cases. The expression and amount of the 28-kDa SpeB protein produced were determined by quantitative Western blotting, and protease activity was measured by a fluorescent enzymatic assay. A high degree of variation in SpeB expression was seen among the isolates, and this variation seemed to correlate with the severity and/or clinical manifestation of the invasive infection. The mean amount of 28-kDa SpeB protein and cysteine protease activity produced by isolates from nonsevere cases was significantly higher than that from STSS cases (P = 0.001). This difference was partly due to the fact that 41% of STSS isolates produced little or no SpeB compared to only 14% of isolates recovered in nonsevere cases. Moreover, the cysteine protease activity among those isolates that expressed SpeB was significantly lower for STSS isolates than for isolates from nonsevere cases (P = 0.001). Increased SpeB production was also inversely correlated with intact M protein expression, and inhibition of cysteine protease activity blocked the cleavage of the surface M protein. Together, the data support the existence of both an "on-off" and a posttranslational regulatory mechanism(s) controlling SpeB production, and they suggest that isolates with the speB gene in the "off" state are more likely to spare the surface M protein and to be isolated from cases of severe rather than nonsevere invasive infection. These findings may have important implications for the role of SpeB in host-pathogen interactions via regulation of the expression of GAS virulence genes and the severity of invasive disease.

Antigens, Bacterial↗
PubMed2000

Genetic relatedness and superantigen expression in group A streptococcus serotype M1 isolates from patients with severe and nonsevere invasive diseases.

The relatedness of group A streptococcal (GAS) strains isolated from 35 Canadian patients with invasive disease of different severity was investigated by a variety of molecular methods. All patients were infected with M1T1 strains and, based on clinical criteria, were classified as severe (n = 21) and nonsevere (n = 14) invasive GAS infection cases. All the M1 strains studied had the emm1.0 allele and the same streptococcal pyrogenic exotoxin (Spe) genotype, speA(+) speB(+) speC speF(+) speG(+) speH smeZ(+) ssa. All isolates had the same speA allotype, speA2. The randomly amplified polymorphic DNA banding pattern with two different primers was identical for all strains, and pulsed field gel electrophoresis analysis showed that 33 and 30 isolates had identical banding patterns after DNA digestion with SfiI or SmaI, respectively; the nonidentical isolates differed from the main pattern by only one band. A relatively high degree of polymorphism in specific regions of the sic gene was observed among isolates; however, this polymorphism was not associated with disease severity. Likewise, although the phenotypic expression of SpeA, SpeB, and SpeF proteins varied among the M1T1 isolates, there was no correlation between the amount of Spe expressed and disease severity. Importantly, mitogenic and cytokine responses induced by partially purified bacterial culture supernatants containing a mixture of expressed superantigens were very similar for isolates from severe and nonsevere cases (P > 0.1). Together, the data indicate that highly related invasive M1T1 isolates, some indistinguishable, can cause disease of varying severity in different individuals. These findings underscore the contribution of host factors to the outcome of invasive GAS infections.

Antigens, Bacterial↗
PubMed2000

Genetic locus for streptolysin S production by group A streptococcus.

Group A streptococcus (GAS) is an important human pathogen that causes pharyngitis and invasive infections, including necrotizing fasciitis. Streptolysin S (SLS) is the cytolytic factor that creates the zone of beta-hemolysis surrounding GAS colonies grown on blood agar. We recently reported the discovery of a potential genetic determinant involved in SLS production, sagA, encoding a small peptide of 53 amino acids (S. D. Betschel, S. M. Borgia, N. L. Barg, D. E. Low, and J. C. De Azavedo, Infect. Immun. 66:1671-1679, 1998). Using transposon mutagenesis, chromosomal walking steps, and data from the GAS genome sequencing project (www.genome.ou.edu/strep. html), we have now identified a contiguous nine-gene locus (sagA to sagI) involved in SLS production. The sag locus is conserved among GAS strains regardless of M protein type. Targeted plasmid integrational mutagenesis of each gene in the sag operon resulted in an SLS-negative phenotype. Targeted integrations (i) upstream of the sagA promoter and (ii) downstream of a terminator sequence after sagI did not affect SLS production, establishing the functional boundaries of the operon. A rho-independent terminator sequence between sagA and sagB appears to regulate the amount of sagA transcript produced versus transcript for the entire operon. Reintroduction of the nine-gene sag locus on a plasmid vector restored SLS activity to the nonhemolytic sagA knockout mutant. Finally, heterologous expression of the intact sag operon conferred the SLS beta-hemolytic phenotype to the nonhemolytic Lactococcus lactis. We conclude that gene products of the GAS sag operon are both necessary and sufficient for SLS production. Sequence homologies of sag operon gene products suggest that SLS is related to the bacteriocin family of microbial toxins.

Amino Acid Sequence↗
PubMed2000

Evaluation of D-xylose and 1% methyl-alpha-D-glucopyranoside fermentation tests for distinguishing Enterococcus gallinarum from Enterococcus faecium.

To determine the validity of the rapid xylose and methyl-alpha-D-glucopyranoside (MDG) fermentation tests in distinguishing Enterococcus gallinarum from Enterococcus faecium, 156 well-characterized clinical isolates of enterococci (55 E. gallinarum, 91 E. faecium, and 10 Enterococcus faecalis isolates) known to be of different clones were examined in a blinded fashion. Species identification was confirmed by PCR of the ddl ligase genes of E. faecium and E. faecalis and the vanC1 gene of E. gallinarum. Xylose tests were performed with D-xylose tablets by using a heavy bacterial suspension and were interpreted after 2 h of incubation. Standard MDG fermentation tests were read after 24 h of incubation. The xylose fermentation test had a sensitivity of 98% (54 of 55) and a specificity of 99% (100 of 101) in distinguishing E. gallinarum from E. faecium and E. faecalis. The standard MDG test had a sensitivity of 100% (55 of 55) and a specificity of 95% (96 of 101) after 24 h. The xylose fermentation test is a simple method, easily incorporated into laboratory protocols, that distinguishes E. gallinarum from E. faecium with high sensitivity and specificity in 2 h. The standard MDG test has high sensitivity and can be useful in ruling out the presence of E. gallinarum but requires overnight incubation.

Bacterial Proteins↗
PubMed2000

Invasive group A streptococcal disease in children and association with varicella-zoster virus infection. Ontario Group A Streptococcal Study Group.

OBJECTIVES: To describe the incidence and clinical features of invasive group A streptococcal (GAS) disease in children in Ontario and determine the risk of invasive GAS infection following chickenpox. METHODS: During 1992-1996, we conducted prospective, active, population-based surveillance for pediatric invasive GAS disease in Ontario, Canada (population: 11 million; 2.5 million children) and reviewed clinical and laboratory records. RESULTS: There were 1.9 cases of invasive GAS disease per 100,000 children per year. Streptococcal toxic shock syndrome (STSS) occurred in 7% of cases and necrotizing fasciitis (NF) in 4% for incidences of.08 and.13 per 100,000 per year, respectively. Case-fatality rates were 56% for STSS, 10% for NF, and 4% overall. The presence of chronic underlying illness other than asthma was associated with death (relative risk [RR]: 11; 95% confidence interval [CI]: 2.4-45). Fifteen percent of children identified had preceding chickenpox infection, which significantly increased the risk for acquisition of invasive GAS disease (RR: 58; 95% CI: 40-85). Children with invasive GAS and recent chickenpox were more likely to have NF (RR: 6.3; 95% CI: 1.8-22.3). CONCLUSIONS: Childhood invasive GAS disease occurs at an incidence similar to the adult population but has a lower rate of STSS and case-fatality. Chickenpox dramatically increases the risk for acquiring invasive GAS disease, and universal chickenpox vaccination could potentially prevent up to 15% of all pediatric invasive GAS disease.

Adolescent↗
PubMed1999

Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. Canadian Bacterial Surveillance Network.

BACKGROUND: Fluoroquinolones are now recommended for the treatment of respiratory tract infections due to Streptococcus pneumoniae, particularly when the isolates are resistant to beta-lactam antibiotics. Although pneumococci with reduced susceptibility to fluoroquinolones have been identified, their prevalence has not been determined in a defined population. METHODS: We performed susceptibility testing on 7551 isolates of S. pneumoniae obtained from surveillance in Canada in 1988 and from 1993 to 1998. Pneumococci with reduced susceptibility to fluoroquinolones (defined as a minimal inhibitory concentration of ciprofloxacin of at least 4 microg per milliliter) were further characterized. We also examined antibiotic prescriptions dispensed in Canadian retail pharmacies. RESULTS: Between 1988 and 1997, fluoroquinolone prescriptions increased from 0.8 to 5.5 per 100 persons per year. The prevalence of pneumococci with reduced susceptibility to fluoroquinolones increased from 0 percent in 1993 to 1.7 percent in 1997 and 1998 (P=0.01). Among adults, the prevalence increased from 1.5 percent in 1993 and 1994 combined to 2.9 percent in 1997 and 1998 combined. The prevalence was higher in isolates from older patients (2.6 percent among those 65 years of age or older vs. 1.0 percent among those 15 to 64 years of age, P<0.001) and among those from Ontario (1.5 percent, vs. 0.4 percent among those from the rest of Canada; P< 0.001). Fluoroquinolone use was greatest among the elderly and in Ontario. The 75 isolates (17 serotypes) of pneumococci with reduced susceptibility to fluoroquinolones were submitted by 40 laboratories in eight provinces. Reduced susceptibility to fluoroquinolones was associated with resistance to penicillin. CONCLUSIONS: The prevalence of pneumococci with reduced susceptibility to fluoroquinolones is increasing in Canada, probably as a result of selective pressure from the increased use of fluoroquinolones.

Adolescent↗
PubMed1999

Virulence of Streptococcus canis from canine streptococcal toxic shock syndrome and necrotizing fasciitis.

The recent recognition of streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) in dogs caused by Streptococcus canis highlights our lack of knowledge regarding the mechanisms of virulence of this organism. Fifteen isolates of S. canis from cases of canine STSS and/or NF were examined for the presence of 10 Streptococcus pyogenes-associated virulence genes by Southern hybridizations using gene probes generated by PCR. The isolates lacked DNA with homology to eight of the 10 gene probes (speA, speB, speC, mf, ssa, scp, hasA, ska) under low stringency conditions. Thirteen and 15 of 15 isolates hybridized with streptolysin O and M protein gene probes, respectively. Twelve of 15 S. canis isolates were resistant to phagocytosis in canine blood. Electron microscopy revealed the presence of proteinaceous cell surface fibrillae. These results suggest that S. canis possesses M proteins and encodes streptolysin O, but lacks some of the other recognized virulence genes with significant homology to those in S. pyogenes.

Amino Acid Sequence↗
PubMed1999

Epidemiologic trends in nosocomial and community-acquired infections due to antibiotic-resistant gram-positive bacteria: the role of streptogramins and other newer compounds.

The Gram-positive cocci have clearly re-emerged as important pathogens world-wide in the past two decades. Staphylococci, including the coagulase-negative staphylococci and Staphylococcus aureus, and the enterococci account for approximately one-third of all blood stream infections and as much as 50% of nosocomial blood stream infections. Although Streptococcus pneumoniae is often considered a community-acquired pathogen, it is also an important cause of nosocomial infection. The hallmark of these Gram-positive pathogens is increasing resistance to available antimicrobial agents. Of particular note is resistance to glycopeptides (vancomycin and teicoplanin), aminoglycosides (high-level), and penicillins among the enterococci (especially E. faecium), resistance to penicillinase-resistant penicillins (oxacillin and methicillin) and fluoroquinolones (ciprofloxacin and ofloxacin) among staphylococci, and resistance to penicillin, other beta-lactams and macrolides among the pneumococci. The recent detection of decreased susceptibility to vancomycin among S. aureus is also quite ominous. In many instances the ability of the clinical laboratory to accurately characterize these resistant isolates is suboptimal, further compounding the problem. Increased understanding of resistance mechanisms and correlations of resistance genes with the phenotypic expression of resistance has allowed for modifications and improvements of reference susceptibility tests and interpretive breakpoints. New compounds for effective therapy of infection with multi-resistant Gram-positive species are clearly needed. To this end, the streptogramin combination, quinupristin/dalfopristin, has demonstrated significant activity against oxacillin-resistant staphylococci, penicillin-resistant streptococci, and vancomycin-resistant E. faecium. Other candidate drugs including Gram-positive active fluoroquinolones (clinafloxacin, grepafloxacin, moxifloxacin, gatifloxacin, and trovafloxacin) and novel compounds such as the everninomicin derivatives (SCH27899), ketolides, and oxazolidinones (linezolid) have been shown to be active against these organisms and are under rapid clinical development.

Anti-Bacterial Agents↗
PubMed1999

Practical approach to the identification of clinically relevant Enterococcus species.

Enterococci have become important nosocomial pathogens, with Enterococcus faecalis and then Enterococcus faecium predominating. Because of the emergence of glycopeptide (vancomycin and teicoplanin) resistance in enterococci, laboratories have been required to screen for resistant strains and to identify them to the species level. This has resulted in the need for accurate identification of species less commonly associated with clinical infections, such as Enterococcus casseliflavus and Enterococcus gallinarum, which are inherently resistant to the glycopeptides. Studies evaluating commonly used commercial identification systems, have found error rates for enterococcal species identification of 2-21% for E. faecalis, 5-9% for E. faecium, and 14-79% for other species. Reporting errors may have adverse effects on the management of clinical infections, as well as in the control of multidrug-resistant strain outbreaks. The purpose of this document is to present a simplified approach to the identification of Enterococcus species that uses a combination of rapid, readily available, and inexpensive tests.

Anti-Bacterial Agents↗
PubMed1999

Two-year survey of Alberta laboratories processing of antenatal group B streptococcal (GBS) screening specimens: implications for GBS screening programs.

We evaluated specimen types received and methods used by laboratories to process screening GBS specimens from pregnant women. Surveys during 1995 and 1997 of all laboratories in the province of Alberta, Canada that culture GBS from screening genital specimens were completed. Between surveys, there was dissemination of information about appropriate culture techniques. Survey completion rates were 100% in both years (38/38 in 1995 and 20/20 in 1997). During 1995 as compared to 1997, laboratories were less likely to a) have a specific written protocol for identification of genital GBS screening specimens (1995: 78.2% versus 1997: 100%, p = 0.08) b) be receiving combined vaginal-anorectal swabs (1995: 18% of all swabs received versus 1997: 60.4%, p < 0.001), and c) be using selective GBS culture media (1995: 45.5% versus 1997: 86.7%, p = 0.01). Regions using screening based approaches for GBS prevention need to ensure that their laboratories are using adequate techniques for GBS detection.

Alberta↗
PubMed1999

Nosocomial bacterial meningitis, including central nervous system shunt infections.

Nosocomial bacterial meningitis and CSF shunt infections result in considerable morbidity and mortality, necessitating an organized and thoughtful approach to prevention, diagnosis, and management. Prophylactic antibiotics appear to reduce the rate of postcraniotomy meningitis often caused by S. aureus. On the other hand, prophylactic antibiotics do not appear to reduce the risk of developing a CSF shunt infection. CSF shunt infections usually require shunt removal and antimicrobial chemotherapy to effect a successful outcome.

Anti-Bacterial Agents↗
PubMed1999

Rapid selection of complement-inhibiting protein variants in group A Streptococcus epidemic waves.

Serotype M1 group A Streptococcus strains cause epidemic waves of human infections long thought to be mono- or pauciclonal. The gene encoding an extracellular group A Streptococcus protein (streptococcal inhibitor of complement) that inhibits human complement was sequenced in 1,132 M1 strains recovered from population-based surveillance of infections in Canada, Finland and the United States. Epidemic waves are composed of strains expressing a remarkably heterogeneous array of variants of streptococcal inhibitor of complement that arise very rapidly by natural selection on mucosal surfaces. Thus, our results enhance the understanding of pathogen population dynamics in epidemic waves and infectious disease reemergence.

Animals↗
PubMed1999

Control of transmission of vancomycin-resistant Enterococcus faecium in a long-term-care facility.

OBJECTIVES: To describe the investigation and control of transmission of vancomycin-resistant enterococci (VRE) in a residential long-term-care (LTC) setting. OUTBREAK INVESTIGATION: A strain of vancomycin-resistant Enterococcus faecium not previously isolated in Ontario colonized five residents of a 254-bed LTC facility in Toronto. The index case was identified when VRE was isolated from a urine culture taken after admission to a local hospital. Screening of rectal swabs from all 235 residents identified four others who were colonized with the same strain of E faecium. CONTROL MEASURES: Colonized residents were cohorted. VRE precautions were established as follows: gown and gloves for resident contact, restriction of contact between colonized and noncolonized residents, no sharing of personal equipment, and daily double-cleaning of residents' rooms and wheelchairs. OUTCOME: Two colonized residents died of causes unrelated to VRE. Although bacitracin therapy (75,000 units four times a day x 14 days) failed to eradicate carriage in two of three surviving residents, both cleared their carriage within 7 weeks. Repeat rectal swabs from 224 residents (91%) 2 months after isolation precautions were discontinued and from 125 residents (51%) 9 months later identified no new cases. Total cost of investigation and control was $12,061 (Canadian). CONCLUSION: VRE may be transmitted in LTC facilities, and colonized LTC residents could become important VRE reservoirs. Control of VRE transmission in LTC facilities can be achieved even with limited resources.

Aged↗
PubMed1999

Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome--a comparative observational study. The Canadian Streptococcal Study Group.

Twenty-one consecutive patients with streptococcal toxic shock syndrome (TSS) between December 1994 and April 1995 were treated with a median dose of 2 g of intravenous immunoglobulin (IVIG)/kg (cases) and were compared with 32 patients with streptococcal TSS between 1992 and 1995 who did not receive IVIG therapy (controls). The outcome measure was 30-day survival. Patient plasma was tested for its ability to inhibit T cell activation induced by the infecting strain. The proportion of cases with 30-day survival was higher than that of the controls with 30-day survival (67% vs. 34%, respectively; P = .02). Multivariate analysis revealed that IVIG administration and a lower Acute Physiology and Chronic Health Evaluation II score were associated with survival; the odds ratio for survival associated with IVIG therapy was 8.1 (95% confidence interval, 1.6-45; P = .009). IVIG therapy enhanced the ability of patient plasma to neutralize bacterial mitogenicity and reduced T cell production of interleukin-6 and tumor necrosis factor alpha. IVIG may be an effective adjunctive therapy for streptococcal TSS, possibly because of its ability to neutralize bacterial exotoxins.

APACHE↗
PubMed1999

Clinical experience with 20 cases of group A streptococcus necrotizing fasciitis and myonecrosis: 1995 to 1997.

During the last decade, there has been a dramatic resurgence of necrotizing fasciitis caused by group A streptococcal disease with mortality rates from 43 to 58 percent. The objective of this study was to review recent clinical experience regarding the diagnosis and management of streptococcal necrotizing fasciitis, including the use of high-dose intravenous immunoglobulin. From April of 1995 to December of 1997, 20 consecutive adult patients meeting clinical and/or histopathologic criteria for streptococcal necrotizing fasciitis were identified in the Toronto area. Of those, 16 (80 percent) were treated with > or = 1 mg/kg of intravenous immunoglobulin. Fourteen men and 6 women ranging in age from 33 to 89 were identified (median age 55.5 years). Sixteen patients (80 percent) with necrotizing fasciitis survived. Ten patients had necrotizing fasciitis alone, none of whom died. Eight patients were identified with myonecrosis and necrotizing fasciitis, three of whom died. The case fatality rate of all patients who received intravenous immunoglobulin was 19 percent (3 of 16) and was not statistically significantly different (p = 1.0) from the case fatality rate of 25 percent (1 of 4) in those patients who did not receive intravenous immunoglobulin. A total of seven patients (35 percent) were diagnosed as having a cause for their signs and symptoms other than necrotizing fasciitis when they initially presented to a physician; one of these patients died. There was no correlation with the M type or the streptococcal pyrogenic exotoxin genotype and outcome.

Adult↗
PubMed1999

Histological and anatomic changes in Barrett's esophagus after antireflux surgery.

OBJECTIVE: The best treatment approach for patients with documented Barrett's esophagus remains controversial. There is currently no well designed prospective study examining the effect of successful antireflux surgery on Barrett's esophagus. METHODS: Fourteen patients with histologically proven Barrett's esophagus underwent standard antireflux surgery followed by careful endoscopic, histological, and symptomatic follow-up beginning at 2-4 wk after surgery. Pre- and postoperative symptoms, patient functional assessment scores, lower esophageal sphincter pressure, and 24-h pH studies were compared, in addition to monitoring patients for evidence of squamous re-epithelialization and dysplasia. RESULTS: Patients demonstrated statistically significant improvement in symptoms, functional assessment scores, lower esophageal sphincter pressure, and 24-h pH assessments after antireflux surgery. Two patients had complete disappearance of short segments (2 and 3 cm) of Barrett's esophagus. Ten additional patients demonstrated evidence of squamous re-epithelialization, although biopsies often showed mixed components of squamous and columnar epithelium. No patients showed progression of dysplastic change, and four patients demonstrated the disappearance of low grade dysplasia throughout the period of the study. CONCLUSION: Successful antireflux surgery can produce at least partial squamous re-epithelialization in Barrett's metaplasia and stabilization or apparent improvement in dysplasia in some patients without the need for long term medication. Continued long term endoscopic and histologic follow-up is still required in all patients with Barrett's esophagus after antireflux surgery.

Adult↗
PubMed1999

Prevalence of antimicrobial resistance in respiratory tract isolates of Streptococcus pneumoniae: results of a Canadian national surveillance study. The Canadian Respiratory Infection Study Group.

From October 1997 to November 1998, 1,180 respiratory tract isolates of Streptococcus pneumoniae were collected from 18 medical centers in 9 of the 10 Canadian provinces. Penicillin-intermediate and -resistant isolates occurred at rates of 14.8 and 6.4%, respectively, and these rates varied considerably by geographic region. Trimethoprim-sulfamethoxazole, tetracycline, and macrolide rates of nonsusceptibility were 12.2, 10.6, and 8.0 to 9.3%, respectively. The most potent agents studied were newer fluoroquinolones.

Anti-Bacterial Agents↗