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Biomedical subjects

D E Low

Publications and source records attributed to D E Low.

At least 91 records · Page 5Linked to original sources
PubMed1999

Molecular characterization of multidrug resistance in Streptococcus mitis.

Antimicrobial resistance was characterized for 14 strains of Streptococcus mitis. HinfI restriction fragment length mapping of gyrA PCR amplicons from three ciprofloxacin-resistant isolates correlated with mutations associated with such resistance in other organisms. By using PCR, seven erythromycin-resistant strains were found to possess either the mef or ermB gene. Hybridization revealed tet(M) in seven tetracycline-resistant isolates.

Drug Resistance, Microbial↗
PubMed1999

Prevalence and mechanisms of macrolide resistance in clinical isolates of group A streptococci from Ontario, Canada.

A total of 3,205 group A streptoccal isolates were collected in 1997 through a private laboratory which serves community physicians in southern Ontario and which represents a population base of 6 million people. Nonsusceptibility to erythromycin was detected for 67 (2.1%) isolates both by disk diffusion and by broth microdilution. Of these, 47 (70%) were susceptible to clindamycin and were found by PCR to possess the mef gene. Of the other 20 strains, 18 and 2 showed inducible and constitutive resistance, respectively, to clindamycin. Nineteen of these strains were shown by PCR to possess the ermTR gene, and a single constitutively resistant strain harbored an ermB gene. Sixteen (24%) erythromycin-resistant strains were also resistant to tetracycline. All were susceptible to penicillin and chloramphenicol.

Anti-Bacterial Agents↗
PubMed1999

In vitro activities of fluoroquinolones against antibiotic-resistant blood culture isolates of viridans group streptococci from across Canada.

Among 418 blood culture isolates of viridans group streptococci obtained between 1995 and 1997, the in vitro rates of nonsusceptibility to penicillin, erythromycin, tetracycline, and trimethoprim-sulfamethoxazole were 28, 29, 24, and 14%, respectively. The most prevalent group (125 strains) was Streptococcus mitis, followed by Streptococcus sanguis (56 strains). For 236 (56%) strains resistant to one or more antibiotics, the ciprofloxacin MIC at which 90% of the isolates were inhibited (MIC(90)) was 4 microg/ml, whereas the MIC(90)s of trovafloxacin, grepafloxacin, and gatifloxacin were 0.25 microg/ml.

Anti-Infective Agents↗
PubMed1999

Risk factors in the pathogenesis of invasive group A streptococcal infections: role of protective humoral immunity.

An impressive change in the epidemiology and severity of invasive group A streptococcal infections occurred in the 1980s, and the incidence of streptococcal toxic shock syndrome cases continues to rise. The reason for the resurgence of severe invasive cases remains a mystery-has there been a change in the pathogen or in host protective immunity? To address these questions, we have studied 33 patients with invasive infection caused by genotypically indistinguishable M1T1 strains of Streptococcus pyogenes who had different disease outcomes. Patients were classified as having severe (n = 21) and nonsevere (n = 12) invasive infections based on the presence or absence of shock and organ failure. Levels of anti-M1 bactericidal antibodies and of anti-streptococcal superantigen neutralizing antibodies in plasma were significantly lower in both groups than in age- and geographically matched healthy controls (P < 0.01). Importantly, the levels of these protective antibodies in plasma samples from severe and nonsevere invasive cases were not different. Together the data suggest that low levels of protective antibodies may contribute to host susceptibility to invasive streptococcal infection but do not modulate disease outcome. Other immunogenetic factors that regulate superantigen responses may influence the severity of systemic manifestations associated with invasive streptococcal infection.

Animals↗
PubMed1998

A clinical score to reduce unnecessary antibiotic use in patients with sore throat.

OBJECTIVE: To validate a score based on clinical symptoms and signs for the identification of group A Streptococcus (GAS) infection in general practice patients with score throat. DESIGN: A single throat swab was used as the gold standard for diagnosing GAS infection. Clinical information was recorded by experienced family physicians on standardized encounter forms. Score criteria were identified by means of logistic regression modelling of data from patients enrolled in the first half of the study. The score was then validated among the remaining patients. SETTING: University-affiliated family medicine centre in Toronto. PATIENTS: A total of 521 patients aged 3 to 76 years presenting with a new upper respiratory tract infection from December 1995 to February 1997. OUTCOME MEASURES: Sensitivity, specificity and likelihood ratios for identification of GAS infection with the score approach compared with throat culture. Proportion of patients prescribed antibiotics, throat culture use, and sensitivity and specificity with usual physician care and with score-based recommendations were compared. RESULTS: A score was developed ranging in value from 0 to 4. The sensitivity of the score for identifying GAS infection was 83.1%, compared with 69.4% for usual physician care (p = 0.06); the specificity values of the 2 approaches were similar. Among patients aged 3 to 14 years, the sensitivity of the score approach was higher than that of usual physician care (96.9% v. 70.6%) (p < 0.05). The proportion of patients receiving initial antibiotic prescriptions would have been reduced 48% by following score-based recommendations compared with observed physician prescribing (p < 0.001), without any increase in throat culture use. CONCLUSIONS: An age-appropriate sore throat score identified GAS infection in children and adults with sore throat better than usual care by family physicians, with significant reductions in unnecessary prescribing of antibiotics. A randomized trial comparing the 2 approaches is recommended to determine the ability of the score approach to reduce unnecessary prescribing of antibiotics during routine clinical encounters.

Adolescent↗
PubMed1998

Comparison of conventional and wire mesh expandable prostheses and surgical bypass in patients with malignant esophagorespiratory fistulas.

BACKGROUND: Patients who present with malignant esophagorespiratory fistula continue to provide a significant palliative challenge to gastroenterologists and surgeons. METHODS: This retrospective series reviewed 29 patients treated with conventional prostheses (13 patients), expandable wire mesh-coated prostheses (12 patients), and surgical bypass with esophageal exclusion (4 patients) between 1982 and 1995. RESULTS: Improvement in dysphagia scores were comparable in all three groups. Fistula occlusion was more successful with expandable prostheses (92%) compared conventional prostheses (77%); however, reinterventions were required more commonly with expandable prostheses, which were also significantly more expensive on a unit cost basis. In selected patients in whom prosthesis placement either was inappropriate or failed, surgical bypass and esophageal exclusion was undertaken. These patients demonstrated good palliation with minimal morbidity and no mortality. CONCLUSIONS: Both conventional and expandable prostheses are safe and reasonably straightforward treatment modalities for patients with esophagorespiratory fistulas. Because of ease of insertion and large luminal diameter, expandable metal prostheses will see increasing use in treatment of these difficult patients; however, conventional prostheses will remain a good alternative, especially in patients with extrinsic esophageal compression. When stent placement is either unsuccessful or inadvisable, physiologically fit patients can undergo surgical bypass and esophageal exclusion with good palliation and minimal morbidity and mortality.

Adenocarcinoma↗
PubMed1998

Resistance issues and treatment implications: pneumococcus, Staphylococcus aureus, and gram-negative rods.

During the last decade there has been an unexpectedly rapid evolution of antimicrobial resistance in the respiratory pathogens for community- and hospital-acquired pneumonia. In order to choose the most optimal therapy for their patients, it is essential that physicians be aware of the prevalence and mechanisms of resistance and their implications on the effectiveness of the various antimicrobials.

Anti-Bacterial Agents↗
PubMed1998

The superbugs: evolution, dissemination and fitness.

Since the introduction of antibiotics, bacteria have not only evolved elegant resistance mechanisms to thwart their effect, but have also evolved ways in which to disseminate themselves or their resistance genes to other susceptible bacteria. During the past few years, research has revealed not only how such resistance mechanisms have been able to evolve and to rapidly disseminate, but also how bacteria have, in some cases, been able to adapt to this new burden of resistance with little or no cost to their fitness. Such adaptations make the control of these superbugs all the more difficult.

Anti-Bacterial Agents↗
PubMed1998

Varying titers of neutralizing antibodies to streptococcal superantigens in different preparations of normal polyspecific immunoglobulin G: implications for therapeutic efficacy.

Inasmuch as normal intravenous polyspecific immunoglobulin G (IVIG) neutralizes the activity of a wide spectrum of superantigens, it may be an efficient adjunctive therapy for diseases associated with superantigen-producing organisms, including severe group A streptococcal diseases. The neutralizing activity against purified superantigens, streptococcal pyrogenic exotoxins (Spe), and a mixture of superantigens present in culture supernatant of clinical group A streptococcal isolates was determined for five IVIG preparations. A significant variation among different IVIG preparations (P < .05) and different lots of the same IVIG brand (P < .044) was found. Neutralization of SpeA activity was significantly lower than that of other streptococcal superantigens (P < .05); however, there was no correlation between SpeA binding and SpeA neutralizing activity in different IVIGs. Plasma samples obtained from patients after IVIG infusion varied in their titers of neutralizing antibodies to culture supernatants prepared from their respective isolates, and this variation paralleled differences in the neutralizing titer of the IVIG lot administered to each patient studied. The study suggests that complete neutralizing activity may be achieved by optimizing the type and/or dose of IVIG used in treatment.

Antibodies, Bacterial↗
PubMed1998

Skin and soft tissue infection: necrotizing fasciitis.

The incidence of necrotizing fasciitis has increased in the past decade as a result of the resurgence severe group A streptococcal infection. Mortality has remained unchanged over the past 60 years, supporting the notion that immune modulators, such as intravenous immunoglobulin, are required to alter the physiological process during the early stages of infection.

Journal Article↗
PubMed1998

The use of Streptococcus pneumoniae nasopharyngeal isolates from healthy children to predict features of invasive disease.

BACKGROUND: The role of sampling nasopharyngeal carriage isolates of Streptococcus pneumoniae to determine characteristics of isolates causing invasive disease has not been established. METHODS: Data were compared from two 1995 studies of S. pneumoniae in Metropolitan Toronto and Peel Region (population, 3.1 million). The first was a prospective survey of nasopharyngeal (NP) carriage in child care centers. The second was a prospective surveillance for all cases of invasive disease. RESULTS: There were 545 NP S. pneumoniae isolates obtained from 532 children and 96 cases of invasive S. pneumoniae disease in children. The prevalences of reduced antibiotic susceptibility in the NP carriage and invasive studies, respectively, were: penicillin (16% vs. 11%, P=0.29); erythromycin (12% vs. 7%, P=0.25); and multiresistant (16% vs. 12%, P=0.34). The power to rule out a difference between the groups was <30% for each comparison. Trimethoprim/sulfamethoxazole resistance was more common in NP carriage isolates than invasive isolates (38% vs. 23%, P=0.02). Serotype 14 was more common in invasive isolates, whereas serogroup 6 was more common in NP carriage isolates. Antibiotic-resistant isolates were predominantly serogroups 6, 19 and 23 in both studies. CONCLUSIONS: Nasopharyngeal carriage isolates of S. pneumoniae reflect the antibiotic susceptibility rates of invasive isolates found in the same period for most antibiotics. However, even a large study like this may have limited power to detect a difference. The most common NP carriage serotypes are the same as the invasive isolates, although the rank order of specific serotypes is different. Routine surveys of S. pneumoniae NP carriage are not feasible because of the cost of serotyping and limited power of the observations, unless sample sizes are extremely large.

Age Factors↗
PubMed1998

Prevalence and characterization of the mechanisms of macrolide, lincosamide, and streptogramin resistance in isolates of Streptococcus pneumoniae.

Of a total of 147 erythromycin-resistant Streptococcus pneumoniae isolates, 64 (43.5%) were resistant to erythromycin, clindamycin, and streptogramin B (MLSB phenotype), 57 of which possessed the ermB gene. Eighty-two (55.8%) were resistant to erythromycin alone (M phenotype), 81 of which possessed the mefE gene. One was erythromycin and streptogramin B resistant but susceptible to clindamycin (MS phenotype) and possessed neither the erm gene nor the mefE gene.

Anti-Bacterial Agents↗
PubMed1998

Expression and characterization of group A Streptococcus extracellular cysteine protease recombinant mutant proteins and documentation of seroconversion during human invasive disease episodes.

A recent study with isogenic strains constructed by recombinant DNA strategies unambiguously documented that a highly conserved extracellular cysteine protease expressed by Streptococcus pyogenes (group A Streptococcus [GAS]) is a critical virulence factor in a mouse model of invasive disease (S. Lukomski, S. Sreevatsan, C. Amberg, W. Reichardt, M. Woischnik, A. Podbielski, and J. M. Musser, J. Clin. Invest. 99:2574-2580, 1997). To facilitate further investigations of the streptococcal cysteine protease, recombinant proteins composed of a 40-kDa zymogen containing a C192S amino acid substitution that ablates enzymatic activity, a 28-kDa mature protein with the C192S replacement, and a 12-kDa propeptide were purified from Escherichia coli containing His tag expression vectors. The recombinant C192S zymogen retained apparently normal structural integrity, as assessed by the ability of purified wild-type streptococcal cysteine protease to process the 40-kDa molecule to the 28-kDa mature form. All three recombinant purified proteins retained immunologic reactivity with polyclonal and monoclonal antibodies. Humans with a diverse range of invasive disease episodes (erysipelas, cellulitis, pneumonia, bacteremia, septic arthritis, streptococcal toxic shock syndrome, and necrotizing fasciitis) caused by six distinct M types of GAS seroconverted to the streptococcal cysteine protease. These results demonstrate that this GAS protein is expressed in vivo during the course of human infections and thereby provide additional evidence that the cysteine protease participates in host-pathogen interactions in some patients.

Animals↗
PubMed1998

Reduced virulence of group A streptococcal Tn916 mutants that do not produce streptolysin S.

Streptolysin S (SLS) is a potent cytolytic toxin produced by nearly all group A streptococci (GAS). SLS-deficient Tn916 insertional mutants were generated from two clinical isolates of GAS, MGAS166s and T18Ps (M serotypes 1 and 18, respectively), by transposon mutagenesis using Tn916 donor strain Enterococcus faecalis CG110. Representative nonhemolytic transconjugants SBNH5 and SB30-2 each harbored a single Tn916 insertion in identical loci. The insertion in SBNH5 was located in the promoter region of an open reading frame, designated sagA, rendering it transcriptionally inactive. Protease, streptolysin O, and DNase activities and the production of M protein remained the same in the nonhemolytic mutants and the wild-type strains, as did the growth rates and exoprotein profiles. Transconjugants were evaluated in an established murine model by injecting the organisms subcutaneously and monitoring the mice for alterations in weight and the development of necrotic lesions. Animals infected with SBNH5, compared to those infected with MGAS166s, gained weight during the first 24 h (+1.15 versus -1.16 g; P < 0.05) and had fewer necrotic lesions (0 versus 7; P = 0.0007). Animals infected with SB30-2, compared to those infected with T18Ps, also gained weight within the first 24 h (+0.54 versus -0.66 g; P < 0.05) and produced fewer necrotic lesions (1 versus 8; P = 0.001). Revertants of the mutants in which Tn916 had been excised regained the hemolytic phenotype and the virulence profile of the wild-type strains. This study demonstrates that SLS-deficient mutants of GAS, belonging to different M serotypes and containing identical Tn916 mutations, are markedly less virulent than their isogenic parents.

Amino Acid Sequence↗
PubMed1998

Opsonic antibodies to the surface M protein of group A streptococci in pooled normal immunoglobulins (IVIG): potential impact on the clinical efficacy of IVIG therapy for severe invasive group A streptococcal infections.

The surface M protein of group A streptococci (GAS) is one of the major virulence factors for this pathogen. Antibodies to the M protein can facilitate opsonophagocytosis by phagocytic cells present in human blood. We investigated whether pooled normal immunoglobulin G (IVIG) contains antibodies that can opsonize and enhance the phagocytosis of type M1 strains of GAS and whether the levels of these antibodies vary for different IVIG preparations. We focused on the presence of anti-M1 antibodies because the M1T1 serotype accounts for the majority of recent invasive GAS clinical isolates in our surveillance studies. The level of anti-M1 antibodies in three commercial IVIG preparations was determined by enzyme-linked immunosorbent assay (ELISA), and the opsonic activity of these antibodies was determined by neutrophil-mediated opsonophagocytosis of a representative M1T1 isolate. High levels of opsonic anti-M1 antibodies were found in all IVIG preparations tested, and there was a good correlation between ELISA titers and opsonophagocytic activity. However, there was no significant difference in the levels of opsonic anti-M1 antibodies among the various IVIG preparations or lots tested. Adsorption of IVIG with M1T1 bacteria removed the anti-M1 opsonic activity, while the level of anti-M3 opsonophagocytosis was unchanged. Plasma was obtained from seven patients with streptococcal toxic shock syndrome who received IVIG therapy, and the level of anti-M1 antibodies was assessed before and after IVIG administration. A significant increase in the level of type M1-specific antibodies was found in the plasma of all patients who received IVIG therapy (P < 0.006). The results reveal another potential mechanism by which IVIG can ameliorate severe invasive group A streptococcal infections.

Animals↗
PubMed1998

Diagnosis of group A streptococcal necrotizing fasciitis by using PCR to amplify the streptococcal pyrogenic exotoxin B gene.

This study evaluated a PCR assay for detection of the streptococcal pyrogenic exotoxin B (speB) gene from tissue biopsy specimens of patients with necrotizing fasciitis. speB was detected in specimens from all 10 patients with necrotizing fasciitis due to group A streptococcus. The assay was negative for all 11 patients without culture or serologic evidence of streptococcal infection. These results suggest that the detection of speB by PCR may be useful for confirming group A streptococcal infection when cultures are negative or not available.

Bacterial Proteins↗
PubMed1998

Streptococcus iniae, a human and animal pathogen: specific identification by the chaperonin 60 gene identification method.

It was recently reported that Streptococcus iniae, a bacterial pathogen of aquatic animals, can cause serious disease in humans. Using the chaperonin 60 (Cpn60) gene identification method with reverse checkerboard hybridization and chemiluminescent detection, we identified correctly each of 12 S. iniae samples among 34 aerobic gram-positive isolates from animal and clinical human sources.

Animals↗