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D E Low

Publications and source records attributed to D E Low.

At least 19 recordsLinked to original sources
PubMed2006

Macrolide resistance in bacteremic pneumococcal disease: implications for patient management.

BACKGROUND: Despite pneumococcal antibiotic resistance rates in excess of 25%, macrolides remain first-line agents for the treatment of community-acquired pneumonia. METHODS: Prospective, population-based surveillance was conducted to identify cases of pneumococcal bacteremia in Toronto and Peel, Canada, between 2000 and 2004. "Macrolide failures" were defined as cases of bacteremia occurring during outpatient treatment with macrolide antibiotics or within 2 days after treatment. Macrolide susceptibility was determined according to Clinical Laboratory Standards Institute guidelines; common macrolide resistance mechanisms were determined by genotyping. RESULTS: During the 5 years of surveillance, there were 1696 episodes of pneumococcal bacteremia (8.5 cases/100,000 population/year), of which 60 (3.5%) were failures of outpatient macrolide therapy. Resistant isolates were more common among cases of bacteremia after failure of macrolide therapy (37 [64%] of 58 cases) than among cases of bacteremia after failure of nonmacrolide antibiotics (16 [22%] of 74 cases; P<.001) or cases of bacteremia that occurred without prior antibiotic therapy (193 [12%] of 1569 cases; P<.001). Macrolide failures were significantly more common among cases of pneumococcal bacteremia with isolates exhibiting an erythromycin MIC of 1 microg/mL than among isolates exhibiting MICs < or = 0.25 microg/mL (3 [38%] of 8 cases vs. 21 [1.5%] of 1394 cases of bacteremia; P<.001). Increases in the MIC to 1 microg/mL were not associated with further increases in the likelihood of macrolide failure. Low-level resistance conferred by mefA and high-level resistance conferred by ermB were equally overrepresented among macrolide failures. CONCLUSIONS: Macrolide resistance contributes to an increased risk of macrolide failure, irrespective of the underlying resistance mechanism or of the degree of elevation in erythromycin MIC.

Bacteremia↗
PubMed2006

NIS vs SAGES: a comparison of national and voluntary databases.

BACKGROUND: Surgical outcomes are increasingly examined in an effort to improve quality and reduce medical error. The Nationwide Inpatient Sample (NIS) is a retrospective, claims-derived and population-based database and the Society of American Gastrointestinal Endoscopic Surgeons (SAGES) Outcomes Project is a prospective, voluntary and specialty surgeon database. We hypothesized that these two sources of outcome data would differ in regard to a single, commonly performed procedure. METHODS: Both the NIS, a national sample of all nonfederal hospital discharges, and the gastroesophageal reflux disease log of the SAGES Outcomes Project were queried for all fundoplications performed between 1999 and 2001 using either ICD-9 procedure code 44.66 or CPT codes 43280 or 43324. Patients with an emergency admission, age <17 years, and/or diagnoses for either esophageal cancer or achalasia were excluded. Both demographic and outcome variables were compared by either t-test or chi-square analysis, with a p value of <0.05 as significant. RESULTS: Both data sets were comparable for age and gender; however, the SAGES group had a higher rate of teaching hospital affiliation (71 vs 48%, p < 0.001). SAGES fundoplications had a consistently higher rate of comorbidities, including Barrett's esophagus (2.3 vs 1.1%, p = 0.005). The NIS fundoplications had a clear trend toward more associated procedures, including cholecystectomy (7.2 vs 2%, p < 0.001). Complication rates for the NIS data set were higher, including pulmonary complications (1.7 vs 0.5%, p = 0.03). No statistically significant differences existed between the two data sets for either length of stay or mortality. CONCLUSIONS: The two databases indicate that fundoplication is an operation with low morbidity and mortality. The SAGES Outcomes Project demonstrated that participating surgeons had a higher affiliation with teaching hospitals, higher reporting of comorbidity, and lower associated procedures than the NIS. Despite having more comorbidity and technical difficulty, patients from the SAGES Outcomes Project had equivalent or lower complication rates.

Databases, Factual↗
PubMed2006

Suspected transmission of methicillin-resistant Staphylococcus aureus between domestic pets and humans in veterinary clinics and in the household.

OBJECTIVE: To describe MRSA infection and colonization in household pets, and transmission of MRSA between animals and humans. METHODS: MRSA infection and colonization in household pets and human contacts were evaluated during investigations initiated after identification of MRSA infection or colonization of a household pet in order to determine if there had been transmission between animals and humans. All MRSA isolates were screened for Panton-Valentine leukocidin (PVL) genes by use of polymerase chain reaction, and isolate relatedness was determined by use of pulsed-field gel electrophoresis (PFGE). RESULTS: Investigations of six situations where MRSA was identified in one or more animals in a household or veterinary facility were performed. MRSA was isolated from 8 animals (5 dogs and 3 cats) with clinical infections, 1 cat that was in contact with 2 infected cats and 14/88 (16%) of household contacts or veterinary personnel. Both animal-to-human and human-to-animal transmission were suspected. An indistinguishable MRSA isolate was recovered from at least one human that was in contact with each animal case. All isolates were classified as Canadian epidemic MRSA-2, the predominant community-associated MRSA clone in humans in Canada. No isolates possessed genes encoding for the PVL. CONCLUSIONS: Transmission of MRSA between humans and animals, in both directions, was suspected. MRSA appears to be an emerging veterinary and zoonotic pathogen.

Animals↗
PubMed2006

A survey of physician's attitudes regarding management of severe group A streptococcal infections.

Intravenous immunoglobulins (IVIG) use in the management of streptococcal toxic shock syndrome remains highly controversial. To evaluate the current management of severe group A streptococcal infections and the feasibility of a randomized controlled trial comparing immunoglobulins versus placebo for streptococcal toxic shock syndrome and/or necrotizing fasciitis, a 32-question mail and web-based survey of Canadian infectious disease specialists was conducted between December 2003 and February 2004. Overall, 172 respondents (90.5%) recommended immunoglobulins as adjunctive treatment of streptococcal toxic shock compared to 67 (35.3%) for fasciitis without toxic shock and 93 (48.9%) for invasive group A streptococcal infections with hypotension. A considerable proportion of respondents agreed that a randomized clinical trial in streptococcal toxic shock (70.1%, 131/187) and necrotizing fasciitis without toxic shock (88.2%, 162/186) would be ethical. From these, a great majority would be willing to enroll patients in a trial comparing IVIG to placebo for streptococcal toxic shock (125/131, 95.4%) and necrotizing fasciitis without shock (152/162, 93.8%). These initial results clearly demonstrate ambivalence in the utilization of intravenous immunoglobulins (IVIG) in invasive group A streptococcal infections in Canada and emphasize the need for further clinical data on immunoglobulin use in streptococcal toxic shock syndrome. They also demonstrate that, although the majority of physicians recommend immunoglobulins, there is important variability between physician recommendations with regard to the indications of use, dose, and time of administration.

Canada↗
PubMed2006

Relative potential for selection of quinolone-resistance-determining-region mutations in Streptococcus pneumoniae by gemifloxacin, gatifloxacin and moxifloxacin.

Serial passage of a clinical isolate of Streptococcus pneumoniae, in the presence of moxifloxacin, gatifloxacin or gemifloxacin, gave rise to resistant isolates. Non-susceptibility as defined by Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) breakpoints arose on Days 10, 11, and 12 with gatifloxacin, gemifloxacin, and moxifloxacin respectively. Moxifloxacin and gatifloxacin selected for a single step quinolone-resistant-determining-region (QRDR) mutation in DNA gyrase (GyrA) on Day 4 and 7 respectively, whereas gemifloxacin selected simultaneously for multi-step mutations in gyrase and topoisomerase IV (ParC) on Day 17 and activated a non-reserpine inhibited efflux mechanism by Day 4. As found in clinical isolates, mutations included Ser-81-Phe and Glu-85-Lys in GyrA and Ser-79-Phe or Asp-83-Tyr in ParC. At high MICs, moxifloxacin showed a previously unreported 4 amino-acid deletion in GyrB as well as a more unusual substitution Ser-79-Leu/Ile in ParC. Gemifloxacin showed a 2- to 16-fold greater activity than moxifloxacin or gatifloxacin against strains with two or more QRDR mutations, however, its potency did not translate to nonsusceptibility and gemifloxacin MIC values were either at or well above the CLSI nonsusceptible breakpoint concentration.

Amino Acid Substitution↗
PubMed2005

An outbreak of methicillin-resistant Staphylococcus aureus skin infections resulting from horse to human transmission in a veterinary hospital.

There are increasing reports of methicillin-resistant Staphylococcus aureus (MRSA) infection and colonization in horses and evidence that MRSA can be transmitted between horses and humans. The objective of this study was to investigate reports of skin infection in personnel working with a foal with community-associated MRSA colonization and subsequent infection. Clinical diagnostic specimens were collected from individuals reporting skin lesions following contact with the affected foal. Nasal and groin screening swabs were collected from other veterinary personnel that attended a voluntary screening clinic. MRSA skin infections were identified in three neonatal intensive care unit personnel. Nasal colonization was subsequently identified in 10/103 (9.7%) other veterinary hospital personnel. Isolates were indistinguishable by pulsed field gel electrophoresis, classified as Canadian epidemic MRSA-5, possessed SCCmecIV, were negative for the Panton-Valentine leukocidin and were multidrug resistant. Transmission to veterinary personnel despite short-term contact with standard protective barriers highlights the potential importance of MRSA as an emerging zoonotic pathogen, and indicates that further evaluation of interspecies transmission of MRSA and means to prevent zoonotic infection are required.

Adult↗
PubMed2005

Hospital-acquired invasive group a streptococcal infections in Ontario, Canada, 1992-2000.

BACKGROUND: A significant proportion of invasive group A streptococcal infections are hospital acquired. No large, prospective studies have characterized this subgroup of cases and evaluated the risk of transmission in hospitals. METHODS: We conducted prospective, population-based surveillance of invasive group A streptococcal infections in Ontario, Canada, from 1992 to 2000. Epidemiologic and microbiologic investigations were conducted to identify cross-transmission. RESULTS: We identified 291 hospital-acquired cases (12.4%) among 2351 cases of invasive group A streptococcal disease. Hospital-acquired invasive group A streptococcal infections are heterogeneous, including surgical site (96 cases), postpartum (86 cases), and nonsurgical, nonobstetrical infections (109 cases). Surgical site infections affected 1 of 100,000 surgical procedures and involved all organ systems. Postpartum infections occurred at a rate of 0.7 cases per 10,000 live births and exhibited an excellent prognosis. Nonsurgical, nonobstetrical infections encompassed a broad range of infectious syndromes (case-fatality rate, 37%). Nine percent of cases were associated with in-hospital transmission. Transmission occurred from 3 of 142 patients with community-acquired cases of necrotizing fasciitis requiring intensive care unit (ICU) admission, compared with 1 of 367 patients with community-acquired cases without necrotizing fasciitis admitted to the ICU and 1 of 1551 patients with other cases (P<.001). Fifteen outbreaks were identified; 9 (60%) involved only 2 cases. Hospital staff were infected in 1 of 15 outbreaks, but colonized staff were identified in 6 (60%) of 10 investigations in which staff were screened. CONCLUSIONS: Presentation of hospital-associated invasive group A streptococcal infections is diverse. Cross-transmission is common; illness occurs in patients but rarely in staff. Isolation of new cases of necrotizing fasciitis and intervention after a single nosocomial case may also prevent transmission.

Adult↗
PubMed2005

Drug-resistant pneumococcal pneumonia: clinical relevance and approach to management.

Community-acquired pneumonia is the most common infectious disease that causes death, with Streptococcus pneumoniae remaining the leading causative pathogen. The worldwide incidence of infections caused by pneumococci resistant to penicillin, macrolides, and other antimicrobial agents has increased at an alarming rate during the past 2 decades. Yet, these agents are still used as first-line empirical therapy in the outpatient setting. There are several reasons for this, including the infrequency of making a pathogen-specific diagnosis, the failure of studies to demonstrate the relevance of resistance, and the infrequency with which clinicians recognize clinical failures. Despite this, there is mounting evidence that supports the practice of using high doses of some antimicrobial agents, a more active antimicrobial agent within a class, or switching to another class of antimicrobial agents when a patient is identified as being at an increased risk of infection with a resistant pneumococcus. There is now information that will allow the physician to identify not only the patient at risk for infection with a resistant pneumococcus but also the antimicrobial class and, in some cases, the agent within the class to which the organism is more likely to be resistant. This will allow clinicians to better define optimal therapy for patients with community-acquired pneumonia.

Community-Acquired Infections↗
PubMed2005

Decreased prevalence of virulence factors among ciprofloxacin-resistant uropathogenic Escherichia coli isolates.

Ciprofloxacin resistance was identified in 18% and 6% of consecutively collected, clinically significant urinary tract isolates of Escherichia coli from inpatients and outpatients, respectively. In comparison to ciprofloxacin-susceptible isolates, there were fewer resistant isolates that expressed beta-hemolysis (outpatient, 9% versus 87%, P < 0.0001; inpatient, 4% versus 76%, P < 0.0001) and that had a papEF genotype, genes encoding P fimbriae (outpatient, 30% versus 70%, P = 0.0004; inpatient, 26% versus 70%, P < 0.0001).

Bacteriuria↗
PubMed2005

Methicillin-resistant Staphylococcus aureus in horses and horse personnel, 2000-2002.

Methicillin-resistant Staphylococcus aureus (MRSA) infection was identified in 2 horses treated at a veterinary hospital in 2000, prompting a study of colonization rates of horses and associated persons. Seventy-nine horses and 27 persons colonized or infected with MRSA were identified from October 2000 to November 2002; most isolations occurred in a 3-month period in 2002. Twenty-seven (34%) of the equine isolates were from the veterinary hospital, while 41 (51%) were from 1 thoroughbred farm in Ontario. Seventeen (63%) of 27 human isolates were from the veterinary hospital, and 8 (30%) were from the thoroughbred farm. Thirteen (16%) horses and 1 (4%) person were clinically infected. Ninety-six percent of equine and 93% of human isolates were subtypes of Canadian epidemic MRSA-5, spa type 7 and possessed SCCmecIV. All tested isolates from clinical infections were negative for the Panton-Valentine leukocidin genes. Equine MRSA infection may be an important emerging zoonotic and veterinary disease.

Animal Husbandry↗
PubMed2004

Community-acquired pneumonia: new management strategies for evolving pathogens and antimicrobial susceptibilities.

Community-acquired pneumonia (CAP) is still one of the leading causes of mortality and morbidity. The most common bacterial cause of CAP is Streptococcus pneumoniae. The increase in antimicrobial resistance has raised concerns about the efficacy of available therapies, and a call for the reassessment of both existing and newer therapeutic agents. Although microbiological breakpoints are useful for monitoring the emergence of resistance, the current National Committee for Clinical Laboratory Standards (NCCLS) guidelines make no distinction between clinical and microbiological breakpoints. Recent changes in NCCLS breakpoints for extended spectrum cephalosporins have provided a more meaningful approach to susceptibility testing and to consideration of the site of infection. Further controversy surrounds the clinical guidelines relating to CAP in terms of which antimicrobial agents should be given empirically to which types of patients. Within this review, the role of monotherapy versus the need for combination antimicrobial therapy, which often includes a macrolide and an extended spectrum cephalosporin such as ceftriaxone, is discussed. This review also discusses the various aspects of antimicrobial susceptibilities of S. pneumoniae, the drivers and influences of increasing resistance, the clinical relevance of this resistance and possible therapeutic options in the face of changing susceptibilities and mixed bacterial aetiologies. New guidelines from the IDSA attempt to embrace these changes.

Anti-Bacterial Agents↗
PubMed2004

Viridans streptococcal septicaemia in neutropenic patients: role of proinflammatory cytokines.

The immunostimulatory activity of viridans streptococcal strains isolated from neutropenic patients with severe sepsis (n=9) or uncomplicated bacteraemia (n=10) was compared. Peripheral blood mononuclear cells from healthy individuals were stimulated with heat-killed bacteria or culture supernatants, and cytokine production assessed. All strains were potent inducers of IL1beta, IL8, and TNFalpha production. Heat-killed bacteria induced consistently higher IL1beta and TNFalpha production than did the cell-free bacterial supernatants (P<0.01). The strains did not induce any proliferative response, nor any significant TNFbeta or IFNgamma production. No difference in cytokine-inducing capacity could be detected between the cohorts of severe and nonsevere isolates. Comparison of strains causing severe and nonsevere episodes in the same patient (n=2) revealed a significantly higher induction of IL1beta by the severe episodes associated isolates as compared to the nonsevere (P<0.04). The study underscores the importance of the host-pathogen interplay in determining the level of inflammation, and hence the severity of disease.

Bacteremia↗
PubMed2004

Clinical and bacteriological efficacy of the ketolide telithromycin against isolates of key respiratory pathogens: a pooled analysis of phase III studies.

A pooled analysis of data from 13 phase III studies of telithromycin in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute sinusitis or group A beta-haemolytic streptococcal pharyngitis and tonsillitis was undertaken. Causative key respiratory tract pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pyogenes) were isolated at entry to the studies from cultures of relevant respiratory samples and tested for their susceptibility to telithromycin, penicillin and macrolides (erythromycin A). The combined clinical and bacteriological efficacy of telithromycin at the post-therapy, test-of-cure visit (days 17-24) was assessed in patients from whom a microbiologically evaluable pathogen was isolated at entry. More than 98% of key respiratory pathogens isolated, including penicillin G- and macrolide (erythromycin A)-resistant strains of S. pneumoniae, demonstrated full or intermediate susceptibility to telithromycin in vitro at the breakpoints of < or = 1.0 mg/L (susceptible) and 2.0 mg/L (intermediate) used for the purpose of evaluating the susceptibility of isolates recovered during the clinical trials. Treatment with telithromycin 800 mg once-daily for 5, 7 or 7-10 days resulted in high rates of clinical cure (88.5%) and a satisfactory bacteriological outcome (88.9%), similar to the figures seen with comparator antibacterial agents. Clinical cure and eradication rates were good for all key respiratory pathogens, including penicillin G- and macrolide (erythromycin A)-resistant S. pneumoniae. The results suggest that telithromycin will provide effective empirical therapy for community-acquired upper and lower respiratory tract infections.

Adolescent↗
PubMed2004

Novel murine model of pneumococcal pneumonia: use of temperature as a measure of disease severity to compare the efficacies of moxifloxacin and levofloxacin.

Surface temperature measured by an infrared temperature-scanning thermometer was used to evaluate disease severity and predict imminent death in a murine model of pneumococcal pneumonia. We showed that a decrease in temperature was associated with increasing severity of disease and concomitant histological changes and also that a temperature of 30 degrees C or less was a predictor of death. Furthermore, viable bacterial counts in the lungs of mice euthanized at a temperature of < or = 30 degrees C were not significantly different from those seen in the lungs of mice allowed to die without intervention. These data support temperature change as a more subtle indicator of outcome than death and demonstrate that this could be used as a reliable end point for euthanasia. To test the utility of our model in a drug trial, we examined the efficacies of moxifloxacin and levofloxacin by using temperature as a measure of disease severity prior to and during treatment. Regardless of the antibiotic used, mice assessed as moderately ill (temperature > or = 32 degrees C) at the start of treatment had better clinical and bacteriological outcomes than mice assessed as severely ill (temperature < 32 degrees C). However, moxifloxacin offered better protection and greater bacterial clearance than did levofloxacin in all infected mice independent of disease severity. This model not only allows a more subtle evaluation of drug efficacy but also ensures a better degree of standardization and a more humane approach to drug efficacy studies involving animals.

Animals↗
PubMed2004

Future trends in antimicrobial chemotherapy: expert opinion on the 43rd ICAAC.

The current document bestows an expert synopsis of key new information presented at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in 2003. Data is presented on the socio-political aspects of and policies on antimicrobial prescribing, novel mechanisms of resistance in Streptococcus pneumoniae, and current epidemiological trends in global resistance. Novel information on new (and existing) antimicrobial agents--new penicillins, cephalosporins, monobactams and oxipenem inhibitors, ketolides, glycopeptides, fluoroquinolones (and hybrids), peptides, daptomycin, aminomethylcyclines, glycylcyclines, and newer formulations of agents such as amoxycillin-clavulanate--provides renewed hope that resistant pathogens can be controlled through use of more potent agents. Improved strategies for the use of existing antimicrobial agents, such as the use of high-dose regimens, short-course therapy, also may delay or reduce the development of resistance and preserve the value of our antibiotic armamentarium.

Anti-Bacterial Agents↗
PubMed2003

Removal of esophageal expandable metal stents: description of technique and review of potential applications.

BACKGROUND: Expandable metallic stents (EMS) have seen wide application in patients with malignant stricture and fistulas. They have not seen wide application for benign disease because of concern over acute complications and long-term sequelae. METHODS: Between June 1999 and October 2000, six patients with EMS in place for malignant stricture (n = 3), benign stricture (n = 1), anastomotic leak (n = 1) and benign esophagorespiratory fistula (n = 1) had their stents endoscopically removed. Removal was performed secondarily to the following complications: secondary stricture (n = 1), epidural abscess (n = 1), diskitis (n = 1), resolution of fistula (n = 2), and resolution of anastomotic leak (n = 1). RESULTS: Four patients had one EMS: Ultraflex (n = 3) and Z-stent (n = 1). In two patients, two stents (Ultraflex and Z-stent) were retrieved simultaneously. No procedurally related complications occurred. Two patients with esophageal cancer required additional stents. All three patients with benign fistula and stricture recovered uneventfully. CONCLUSIONS: The safe removal of current brands of EMS may facilitate the wider application of these devices to include selective patients with benign disease.

Adult↗