Donald E. Low

Decreased Susceptibility of Streptococcus pneumoniae to Fluoroquinolones in Canada

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.

Invasive group a streptococcal infections in Ontario, Canada

BACKGROUND Several reports suggest that the incidence of invasive group A streptococcal infections, including streptococcal toxic shock syndrome and necrotizing fasciitis, is increasing. METHODS During 1992 and 1993 we conducted prospective, population-based surveillance of invasive group A streptococcal disease in Ontario, Canada. We reviewed clinical and laboratory records, searched for secondary cases of invasive disease, and cultured specimens from household contacts. RESULTS We identified 323 patients with invasive group A streptococcal infections, for an annual incidence of 1.5 cases per 100,000 population. The rates were highest in young children and the elderly. Fifty-six percent of the patients had underlying chronic illness. Risk factors for disease included infection with the human immunodeficiency virus, cancer, diabetes, alcohol abuse, and chickenpox. The most common clinical presentations were soft-tissue infection (48 percent), bacteremia with no septic focus (14 percent), and pneumonia (11 percent). Necrotizing fasciitis occurred in 6 percent of patients, and toxic shock in 13 percent. The mortality rate was 15 percent overall, but it was 29 percent among those over 64 years of age (P<0.001) and 81 percent among those with toxic shock (P<0.001). Fourteen percent of the cases were nosocomial, and 4 percent occurred in nursing home residents, often in association with disease outbreaks. Invasive disease occurred in 2 household contacts of patients with infection, for an estimated risk of 3.2 per 1000 household contacts (95 percent confidence interval, 0.39 to 12 per 1000). CONCLUSIONS The elderly and those with underlying medical conditions are at greatest risk for invasive group A streptococcal disease, toxic shock, and necrotizing fasciitis. Invasive steptococcal infection is associated with a substantial risk of transmission in households and health care institutions.

Intravenous Immunoglobulin Therapy for Streptococcal Toxic Shock Syndrome—A Comparative Observational Study

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.

Population-Based Surveillance for Group A Streptococcal Necrotizing Fasciitis: Clinical Features, Prognostic Indicators, and Microbiologic Analysis of Seventy-Seven Cases

PURPOSE To determine the incidence of group A streptococcal necrotizing fasciitis in Ontario, Canada, and to describe the clinical features, outcome, and microbiologic characteristics of this infection. PATIENTS AND METHODS Prospective, population-based surveillance for invasive group A streptococcal infections was conducted in Ontario from November 1991 to May 1995. All 77 patients meeting clinical and/or histopathologic criteria for streptococcal necrotizing fasciitis were included. Demographic and clinical information was obtained by patient interviews and chart review. Group A streptococci were characterized by M-protein and T-agglutination typing, and polymerase chain reaction (PCR) detection of streptococcal pyrogenic exotoxin genes A and C (speA; speC). RESULTS The incidence of group A streptococcal necrotizing fasciitis increased during the study from 0.085 per 100,000 population in the first year to 0.40 per 100,000 population in the last year (P < 0.001). The median age of cases was 57.5 years and the rate of disease increased with increasing age. Seventy-nine percent of cases were community-acquired, 11% were nosocomial, and 10% were acquired in a nursing home. Forty-seven percent of cases were associated with the presence of streptococcal toxic shock syndrome (Strep TSS) and 46% were bacteremic. Thirty-four percent of cases died and mortality was correlated with increasing age (P = 0.006), presence of hypotension (P = 0.01), and bacteremia (P = 0.03). The most common streptococcal serotypes were M1 (35%) and M3 (25%). Forty-one percent of strains possessed the speA gene and 30% the speC gene. Outcome was not correlated with M-type or the presence of spe genes. CONCLUSIONS The incidence of necrotizing fasciitis caused by group A streptococcus increased in Ontario between 1992 and 1995. Elderly individuals were more likely to acquire the disease and to die from it. Mortality because of streptococcal necrotizing fasciitis was also associated with the presence of hypotension, Strep TSS, or bacteremia, but not with M-type or the presence of pyrogenic exotoxin genes.

Antiviral Therapy and Outcomes of Influenza Requiring Hospitalization in Ontario, Canada

BACKGROUND We conducted a prospective cohort study to assess the impact of antiviral therapy on outcomes of patients hospitalized with influenza in southern Ontario, Canada. METHODS Patients admitted to Toronto Invasive Bacterial Diseases Network hospitals with laboratory-confirmed influenza from 1 January 2005 through 31 May 2006 were enrolled in the study. Demographic and medical data were collected by patient and physician interview and chart review. The main outcome evaluated was death within 15 days after symptom onset. RESULTS Data were available for 512 of 541 eligible patients. There were 185 children (<15 years of age), none of whom died and none of whom were treated with antiviral drugs. The median age of the 327 adults was 77 years (range, 15-98 years), 166 (51%) were male, 245 (75%) had a chronic underlying illness, and 216 (71%) had been vaccinated against influenza. Of the 327 adult patients, 184 (59%) presented to the emergency department within 48 h after symptom onset, 52 (16%) required intensive care unit admission, and 27 (8.3%) died within 15 days after symptom onset. Most patients (292 patients; 89%) received antibacterial therapy; 106 (32%) were prescribed antiviral drugs. Treatment with antiviral drugs active against influenza was associated with a significant reduction in mortality (odds ratio, 0.21; 95% confidence interval, 0.06-0.80; n=100, 260). There was no apparent impact of antiviral therapy on length of stay in survivors. CONCLUSIONS There is a significant burden of illness attributable to influenza in this highly vaccinated population. Treatment with antiviral drugs was associated with a significant reduction in mortality.

Invasive Infections Due to a Fish Pathogen, Streptococcus iniae

BACKGROUND Streptococcus iniae is a pathogen in fish, capable of causing invasive disease and outbreaks in aquaculture farms. During the winter of 1995-1996 in the greater Toronto area there was a cluster of four cases of invasive S. iniae infection in people who had recently handled fresh, whole fish from such farms. METHODS We conducted a prospective and retrospective community-based surveillance for cases of S. iniae infection in humans. To obtain a large sample of isolates, we studied cultures obtained from the surface of fish from aquaculture farms. Additional isolates were obtained from the brains of infected tilapia (oreochromis species). All the isolates were characterized by pulsed-field gel electrophoresis (PFGE). RESULTS During one year, our surveillance identified a total of nine patients with invasive S. iniae infection (cellulitis of the hand in eight and endocarditis in one). All the patients had handled live or freshly killed fish, and eight had percutaneous injuries. Six of the nine fish were tilapia, which are commonly used in Asian cooking. Thirteen additional S. iniae isolates (2 from humans and 11 from infected tilapia) were obtained from normally sterile sites. The isolates from the nine patients were indistinguishable by PFGE and were highly related to the other clinical isolates. There was substantial genetic diversity among the 42 surveillance isolates from the surface of fish, but in 10 isolates the PFGE patterns were identical to those from the patients with S. iniae infection. CONCLUSIONS S. iniae can produce invasive infection after skin injuries during the handling of fresh fish grown by aquaculture. We identified a clone of S. iniae that causes invasive disease in both humans and fish.

Clinical Prevalence, Antimicrobial Susceptibility, and Geographic Resistance Patterns of Enterococci: Results from the SENTRY Antimicrobial Surveillance Program, 1997–1999

As part of the SENTRY Antimicrobial Resistance Surveillance Program, a total of 4998 strains of enterococci isolated from 1997 to 1999 were processed. The occurrence of enterococcal infections by species and site of infection was analyzed, as were the occurrence of vancomycin-resistant enterococci (VRE) and their resistance phenotypes and genotypes. Trends in antimicrobial susceptibility to a variety of agents (including experimental compounds) were also reported. Enterococci accounted for >9% of isolates from all bloodstream infections (BSIs) in North America. Ampicillin was active against strains from Latin America and Europe but not against those from the United States and Canada. US isolates were considerably more resistant to vancomycin (17% resistant strains in 1999) than were those from patients in the rest of the world. The highest proportion of VRE was observed among BSI isolates (81.7%). Quinupristin-dalfopristin, chloramphenicol, and doxycycline were the most active agents tested against VRE. The results of this study confirm the worldwide trend in increasing occurrence of enterococci and the emerging pattern of antimicrobial resistance among such isolates.

Predicting Antimicrobial Resistance in Invasive Pneumococcal Infections

BACKGROUND The prevalence of multiantimicrobial resistance among Streptococcus pneumoniae continues to increase worldwide. In patients presenting with infection possibly due to pneumococci, recognition of risk factors that would identify those likely to have an antibiotic-resistant isolate might assist clinicians in choosing the most appropriate empirical therapy. METHODS A prospective cohort study of invasive pneumococcal infection was conducted in Toronto, Canada. Risk factors for antimicrobial resistance were evaluated by means of univariate and multivariate modeling. RESULTS A total of 3339 patients with invasive pneumococcal infection were identified between 1995 and 2002. Multivariate modeling revealed that risk factors for infection with penicillin-resistant as opposed to penicillin-susceptible pneumococci were year of infection (odds ratio [OR], 1.28; P < .001), absence of chronic organ system disease (OR, 1.72; P = .03), and previous use of penicillin (OR, 2.47; P = .006), trimethoprim-sulfamethoxazole (TMP-SMX; OR, 5.97; P < .001), and azithromycin (OR, 2.78; P = .05). Infection with TMP-SMX-resistant pneumococci was associated with absence of chronic organ system disease (OR, 1.64; P = .001) and with previous use of penicillin (OR, 1.71; P = .03), TMP-SMX (OR, 4.73; P < .001), and azithromycin (OR, 3.49; P = .001). Infection with macrolide-resistant isolates was associated with previous use of penicillin (OR, 1.77; P = .03), TMP-SMX (OR, 2.07; P = .04), clarithromycin (OR, 3.93; P < .001), and azithromycin (OR, 9.93; P < .001). Infection with fluoroquinolone-resistant pneumococci was associated with previous use of fluoroquinolones (OR, 12.1; P < .001), current residence in a nursing home (OR, 12.9; P < .001), and nosocomial acquisition of pneumococcal infection (OR, 9.94; P = .003). CONCLUSIONS Knowledge of antimicrobial use during the 3 months before infection is crucial for determining appropriate therapy for a patient presenting to the hospital with an illness for which S. pneumoniae is a possible cause. Nosocomial acquisition and nursing home acquisition are significant risk factors for infection with fluoroquinolone-resistant pneumococci.

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

ABSTRACT 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.

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

Methicillin-resistant Staphylococcus aureus was isolated from horses and horse personnel in a pattern suggestive of interspecies transmission of a human-origin clone.