At the threshold: defining clinically meaningful resistance thresholds for antibiotic choice in community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia caused by Streptococcus pneumoniae is a major source of morbidity and mortality. Macrolide antibiotics are recommended as empirical first-line therapy for patients with community-acquired pneumonia. Guidelines suggest a 25% rate of high-level macrolide resistance in the community as the threshold beyond which macrolides should not be used. We evaluated the implications of this threshold for clinical failure rates. METHODS: We developed a theoretical model linking the prevalence of macrolide resistance to patient outcomes, based on the epidemiological concept of risk difference. We estimated the risk of clinical failure as a function of the likelihood and impact of discordant therapy and of the probability of clinical failure even in the presence of optimal therapy. The model was parameterized on the basis of the best available data derived from the published medical literature, and clinical failures were valued monetarily using an expected net benefit approach. RESULTS: Under the proposed 25% resistance threshold, the risk difference for such therapy would be 1.2% (95% credible interval, 0.5%-3.1%) for death, 1.6% (95% credible interval, 0.5%-3.2%) for bacteremia, and 3.3% (95% credible interval, 1.1%-5.7%) for prolonged clinical course; excess risks of death were valued at >$10,000 per empirical treatment of community-acquired pneumonia and were further elevated in high-risk populations. Excluding low-level resistance resulted in a 4-fold underestimation of projected risks. CONCLUSION: A 25% resistance threshold that fails to consider low-level resistance will result in high excess rates of morbidity and mortality because of discordant therapy. Whether projected failure rates are classified as unacceptable is an important health policy question, because risk of clinical failure needs to be weighed against other considerations.

Surveillance for hospital outbreaks of invasive group a streptococcal infections in Ontario, Canada, 1992 to 2000.

BACKGROUND: Streptococcus pyogenes can cause severe disease in the individual patient and dramatic hospital outbreaks. OBJECTIVE: To describe the epidemiology of hospital outbreaks of invasive group A streptococcal infection in order to understand the potential benefit of proposed outbreak investigation and management strategies. DESIGN: Prospective, population-based surveillance. SETTING: Short-term care hospitals in Ontario, Canada. PATIENTS: Persons with a positive culture for group A streptococcus from a normally sterile site between 1 January 1992 and 31 December 2000. MEASUREMENTS: Laboratory-based surveillance identified patients with nosocomial invasive group A streptococcal infection. Epidemiologic and microbiological investigations were used to detect transmission. RESULTS: Of 2351 cases of invasive group A streptococcal disease, 291 (12%) were hospital acquired. Twenty-nine (10%) nosocomial cases occurred as part of 20 outbreaks. Seventy percent (14 of 20) of outbreaks involved nonsurgical, nonobstetric patients. Community-acquired cases initiated 25% of outbreaks; most were cases of necrotizing fasciitis in patients admitted to the intensive care unit. Outbreaks were small (median, 2 cases [range, 2 to 10 cases]) and short (median duration, 6 days [range, 0 to 30 days]). The median time between the first 2 cases was 4.5 days. The most common mode of propagation was patient-to-patient transmission. A staff carrier was the primary mode of transmission in 2 (10%) outbreaks, but 1 or more health care workers were colonized with the outbreak strain in 6 of 18 (33%) other outbreaks. LIMITATIONS: Some outbreaks with 1 case of invasive disease may have been missed; advice provided to participating hospitals may have reduced the number and size of outbreaks. CONCLUSIONS: Practices to prevent hospital transmission of group A streptococci should include isolation of patients admitted to the intensive care unit with necrotizing fasciitis, investigation after a single nosocomial case, and emphasis on identifying and treating health care worker carriers on surgical and obstetric services and patient reservoirs on other wards.

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.

Patient contact recall after SARS exposure.

We reinterviewed healthcare workers who had been exposed to a patient with severe acute respiratory syndrome (SARS) in an intensive care unit to evaluate the effect of time on recall reliability and willingness to report contact activities and infection control precautions. Healthcare workers reliably recalled events 6 months after exposure.

Resistance to antibiotics: administrative response to the challenge.

The authors discuss antibiotic resistance within a conceptual framework that illustrates the dynamic relationships among antibiotic, patient, and population factors. The complexity of these interactions makes it unlikely that any single intervention or approach will adequately address the problem of increasing rates of antibiotic resistance. A case study focused on Streptococcus pneumoniae in the context of community-acquired pneumonia provides a detailed examination of the manner in which antibiotic use, expenditures, and microbial resistance are affected by an administrative reimbursement restriction implemented by a single government payer.

Clinical and epidemiologic features of group a streptococcal pneumonia in Ontario, Canada.

BACKGROUND: Since the 1960s, group A streptococcus (GAS) has accounted for less than 1% of cases of community-acquired pneumonia. During the past 2 decades there has been a resurgence of invasive GAS infection, but no large study of GAS pneumonia has been performed. METHODS: To determine the clinical and epidemiologic features of GAS pneumonia, we conducted prospective, population-based surveillance of all invasive GAS infection in residents of Ontario from January 1, 1992, through December 31, 1999. RESULTS: Of 2079 cases of invasive GAS infection, 222 (11%) represented GAS pneumonia. The incidence of GAS pneumonia ranged from 0.16 per 100 000 in 1992 to 0.35 per 100 000 in 1999. Most cases were community acquired (81%). Forty-four percent of nursing home-acquired cases occurred during outbreaks. The case fatality rate was 38% for GAS pneumonia, compared with 12% for the entire cohort with invasive GAS infection and 26% for patients with necrotizing fasciitis. The presence of streptococcal toxic shock syndrome (odds ratio, 19; 95% confidence interval, 8.4-42; P =.001) and increasing age (odds ratio per decade, 1.45; 95% confidence interval, 1.2-1.7; P<.001) were associated with fatal outcome. Time to death was rapid, with a median of 2 days despite antimicrobial therapy and supportive measures. CONCLUSIONS: Group A streptococcal pneumonia is a common form of invasive GAS disease but remains an uncommon cause of community-acquired pneumonia. Progression is rapid despite appropriate therapy. The incidence is similar to, and the case fatality rate higher than, that of necrotizing fasciitis.