Bartlett Infectious Diseases Review: April 30, 2004
Bartlett Infectious Diseases Review: April 30, 2004
Mathers Dunbar L, Hassman J, Tellier G. Efficacy and tolerability of once-daily oral telithromycin compared with clarithromycin for the treatment of community-acquired pneumonia in adults. Clin Ther. 2004;26:48-62.
The investigators present a randomized, double-blind, controlled trial in 54 centers to determine the efficacy and safety of telithromycin for patients with community-acquired pneumonia (CAP). Participants were adults with typical symptoms and x-ray confirmation of pneumonia without prior therapy. Participants were given 10-day courses of either oral telithromycin 800 mg once daily or clarithromycin 500 mg twice daily. Among 416 evaluable patients, the cure rates were 88% in both groups. Streptococcus pneumoniae was recovered from pretreatment sputum in 62 patients; follow-up cultures after therapy showed eradication in 57 (92%). Most of the patients were not seriously ill as indicated by a Pneumonia Patient Outcomes Research Team (PORT) category of I or II in 87% and the fact that 96% were managed entirely as outpatients. Sputum cultures yielded a possible pathogen in 21% of participants, primarily S pneumoniae or Haemophilus influenzae; atypical agents were found in 26 (8%) according to serologic tests, polymerase chain reaction and urinary antigen for Legionella. There was just 1 patient with Legionnaire's disease. Both drugs were well tolerated, with only 3% requiring discontinuation because of adverse reactions. These results are summarized in Table 1 .
The authors conclude that telithromycin is safe and effective in the treatment of adult patients with CAP
Comment: This review is included because of the anticipated release of telithromycin (Ketek) in the near future. This drug is a new class and will target community-acquired respiratory-tract infections. Ketolides represent a structural modification of macrolides that permit more tight binding to ribosomal RNA for enhanced antibacterial potency. It shows good in vitro activity vs common respiratory pathogens, including S pneumoniae (both penicillin-resistant and erythromycin-resistant strains), H influenzae, Moraxella catarrhalis, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila. The pharmacologic profile shows a long half-life permitting once-daily administration. The drug will be available only for oral administration.
Houck PM, Bratzler DW, Nsa W, Ma A, Bartlett JG. Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med. 2004;164:637-644.
This is a report from the Centers for Medicare and Medicaid Services to determine the importance of antibiotic timing in patients who are hospitalized with CAP. This is a retrospective study based on medical records from a national random sample of Medicare patients > 65 years who were hospitalized with x-ray-confirmed CAP from July 1998 through March 1999. During this time, there were 13,771 patients with CAP who had not been previously treated with antibiotics. Most of these patients were age 75-84 years; most were admitted from the community rather than nursing homes (79%); and most were seriously ill as indicated by PORT class IV (47%) or V (24%). The time from registration to first dose of antibiotics was within 4 hours for 61% and within 8 hours for 86%. The overall mortality was 7.0% in the hospital and 12.0% for 30 days following admission. The results of the analysis showed that hospital mortality and 30-day mortality were significantly better when antibiotics were given within 4 hours. This was also associated with a decreased length of stay. The results are summarized in Table 2 .
The authors conclude that antibiotic administration within 4 hours of hospital registration is associated with a significant decrease in mortality and length of stay among Medicare patients.
Comment: This is a retrospective review and differences in the outcome seem modest, but they become far more compelling when considering the size of the denominator and implications for health policies. This study represents the sequel to a similar previous report by Meehan and colleagues that showed a significant difference in mortality when antibiotics were given within 8 hours of registration in a Medicare population. That led to the "8-hour rule," which is a performance indicator by which hospitals are evaluated. The summary above suggests that the 8-hour rule may now become the "4-hour rule," which may seem logistically difficult for some, especially those in busy, urban emergency rooms in which the length of stay prior to any evaluation often exceeds 4 hours. Nevertheless, the review indicated that this performance indicator is currently obliged in 60% of cases; the supporting data are robust, the conclusion is logical, the P value was003, and the outcome evaluated was the most important of all -- mortality. These observations would seem to make a strong case.
Law C, Amsden GW. Single dose azithromycin for respiratory tract infections. Ann Pharmacother. 2004;38:433-439.
The investigators performed a literature review to determine the pharmacology, efficacy, and safety data for single-dose azithromycin for treatment of respiratory-tract infections Three topics are reviewed, including otitis, CAP and tonsillitis. In the CAP category there were 2 studies reviewed: The first was a comparison of azithromycin given in a single, 1500-mg total dose vs 1500 mg over 5 days (500 mg on day 1 followed by 250 mg/day for days 2-5). This study included 96 evaluable patients, and the cure rates were 98% in each group. These results are summarized in Table 3 .
Preliminary results were provided for a second study that included 178 patients hospitalized with CAP who were randomized to (1) single-dose oral azithromycin, 1.5 g; (2) oral azithromycin, 500 mg/day for 3 days; and (3) clarithromycin, 250 mg twice daily for 10 days. The initial results that were presented at the Fifth International Conference on the Macrolides in Seville, Spain, January 26, 2000 (Abstract 4.34) showed cure rates of 100%, 98.3%, and 98.3% in the 3 groups, respectively. The author notes that the single dose is justified by the high bioavailability and prolonged half-life of the drug. Some patients have gastrointestinal intolerance to the high dose, but this can usually be corrected by administration with food that does not alter bioavailability. The investigators conclude that this preliminary experience is promising, but large-scale trials are necessary before this can be considered standard care in adults with respiratory-tract infections.
Comment: There appears to be a rush for shorter courses of antibiotics, and this presumably represents the extreme. Nevertheless, the results seem promising and may offer a particular advantage in some patients with anticipated adherence problems.
Woo PC, Lau SK, Tsoi HW, et al. Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia. Lancet. 2004;363:841-845.
The investigators cloned and purified the nucleocapsid protein and spike polypeptide of severe acute respiratory syndrome-coronavirus (SARS-CoV) and examined their immunogenicity with sera from patients with SARS pneumonia. These produced prominent, immunoreactive bands with both antigens from patients and were negative in controls. The specificity of the immunoglobulin G (IgG) antibody test by enzymeimmunoassay with positive samples with the 2 western-blot assays was 100% and sensitivity was 94.3%. Testing involved sera from 149 healthy blood donors who donated 3 years previously, 400 healthy blood donors who donated during the SARS epidemic, and 131 pediatric inpatients without pneumonia. The results showed a positive test in 3/400 healthy blood donors and 1/131 pediatric patients without pneumonia. All 4 were confirmed by 2 western-blot assays. These results indicate infection with SARS-CoV in 3/400 (0.8%) healthy blood donors during the epidemic and 1/131 (0.8%) pediatric patients hospitalized without pneumonia. The researchers conclude that SARS pneumonia occurred in 1728 patients out of 7 million persons in Hong Kong, China, for an attack rate of 0.025%; the rate of nonpneumonic SARS-CoV infection was about 0.48%. A review of the 4 cases indicated that 3 were asymptomatic healthy blood donors, and the pediatric patient was hospitalized with a brief, self-limited fever.
Comment: The conclusion is that asymptomatic infection with SARS-CoV may be 10-20 times more frequent than SARS as classically described.
Mathers Dunbar L, Hassman J, Tellier G. Efficacy and tolerability of once-daily oral telithromycin compared with clarithromycin for the treatment of community-acquired pneumonia in adults. Clin Ther. 2004;26:48-62.
The investigators present a randomized, double-blind, controlled trial in 54 centers to determine the efficacy and safety of telithromycin for patients with community-acquired pneumonia (CAP). Participants were adults with typical symptoms and x-ray confirmation of pneumonia without prior therapy. Participants were given 10-day courses of either oral telithromycin 800 mg once daily or clarithromycin 500 mg twice daily. Among 416 evaluable patients, the cure rates were 88% in both groups. Streptococcus pneumoniae was recovered from pretreatment sputum in 62 patients; follow-up cultures after therapy showed eradication in 57 (92%). Most of the patients were not seriously ill as indicated by a Pneumonia Patient Outcomes Research Team (PORT) category of I or II in 87% and the fact that 96% were managed entirely as outpatients. Sputum cultures yielded a possible pathogen in 21% of participants, primarily S pneumoniae or Haemophilus influenzae; atypical agents were found in 26 (8%) according to serologic tests, polymerase chain reaction and urinary antigen for Legionella. There was just 1 patient with Legionnaire's disease. Both drugs were well tolerated, with only 3% requiring discontinuation because of adverse reactions. These results are summarized in Table 1 .
The authors conclude that telithromycin is safe and effective in the treatment of adult patients with CAP
Comment: This review is included because of the anticipated release of telithromycin (Ketek) in the near future. This drug is a new class and will target community-acquired respiratory-tract infections. Ketolides represent a structural modification of macrolides that permit more tight binding to ribosomal RNA for enhanced antibacterial potency. It shows good in vitro activity vs common respiratory pathogens, including S pneumoniae (both penicillin-resistant and erythromycin-resistant strains), H influenzae, Moraxella catarrhalis, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila. The pharmacologic profile shows a long half-life permitting once-daily administration. The drug will be available only for oral administration.
Houck PM, Bratzler DW, Nsa W, Ma A, Bartlett JG. Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med. 2004;164:637-644.
This is a report from the Centers for Medicare and Medicaid Services to determine the importance of antibiotic timing in patients who are hospitalized with CAP. This is a retrospective study based on medical records from a national random sample of Medicare patients > 65 years who were hospitalized with x-ray-confirmed CAP from July 1998 through March 1999. During this time, there were 13,771 patients with CAP who had not been previously treated with antibiotics. Most of these patients were age 75-84 years; most were admitted from the community rather than nursing homes (79%); and most were seriously ill as indicated by PORT class IV (47%) or V (24%). The time from registration to first dose of antibiotics was within 4 hours for 61% and within 8 hours for 86%. The overall mortality was 7.0% in the hospital and 12.0% for 30 days following admission. The results of the analysis showed that hospital mortality and 30-day mortality were significantly better when antibiotics were given within 4 hours. This was also associated with a decreased length of stay. The results are summarized in Table 2 .
The authors conclude that antibiotic administration within 4 hours of hospital registration is associated with a significant decrease in mortality and length of stay among Medicare patients.
Comment: This is a retrospective review and differences in the outcome seem modest, but they become far more compelling when considering the size of the denominator and implications for health policies. This study represents the sequel to a similar previous report by Meehan and colleagues that showed a significant difference in mortality when antibiotics were given within 8 hours of registration in a Medicare population. That led to the "8-hour rule," which is a performance indicator by which hospitals are evaluated. The summary above suggests that the 8-hour rule may now become the "4-hour rule," which may seem logistically difficult for some, especially those in busy, urban emergency rooms in which the length of stay prior to any evaluation often exceeds 4 hours. Nevertheless, the review indicated that this performance indicator is currently obliged in 60% of cases; the supporting data are robust, the conclusion is logical, the P value was003, and the outcome evaluated was the most important of all -- mortality. These observations would seem to make a strong case.
Law C, Amsden GW. Single dose azithromycin for respiratory tract infections. Ann Pharmacother. 2004;38:433-439.
The investigators performed a literature review to determine the pharmacology, efficacy, and safety data for single-dose azithromycin for treatment of respiratory-tract infections Three topics are reviewed, including otitis, CAP and tonsillitis. In the CAP category there were 2 studies reviewed: The first was a comparison of azithromycin given in a single, 1500-mg total dose vs 1500 mg over 5 days (500 mg on day 1 followed by 250 mg/day for days 2-5). This study included 96 evaluable patients, and the cure rates were 98% in each group. These results are summarized in Table 3 .
Preliminary results were provided for a second study that included 178 patients hospitalized with CAP who were randomized to (1) single-dose oral azithromycin, 1.5 g; (2) oral azithromycin, 500 mg/day for 3 days; and (3) clarithromycin, 250 mg twice daily for 10 days. The initial results that were presented at the Fifth International Conference on the Macrolides in Seville, Spain, January 26, 2000 (Abstract 4.34) showed cure rates of 100%, 98.3%, and 98.3% in the 3 groups, respectively. The author notes that the single dose is justified by the high bioavailability and prolonged half-life of the drug. Some patients have gastrointestinal intolerance to the high dose, but this can usually be corrected by administration with food that does not alter bioavailability. The investigators conclude that this preliminary experience is promising, but large-scale trials are necessary before this can be considered standard care in adults with respiratory-tract infections.
Comment: There appears to be a rush for shorter courses of antibiotics, and this presumably represents the extreme. Nevertheless, the results seem promising and may offer a particular advantage in some patients with anticipated adherence problems.
Woo PC, Lau SK, Tsoi HW, et al. Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia. Lancet. 2004;363:841-845.
The investigators cloned and purified the nucleocapsid protein and spike polypeptide of severe acute respiratory syndrome-coronavirus (SARS-CoV) and examined their immunogenicity with sera from patients with SARS pneumonia. These produced prominent, immunoreactive bands with both antigens from patients and were negative in controls. The specificity of the immunoglobulin G (IgG) antibody test by enzymeimmunoassay with positive samples with the 2 western-blot assays was 100% and sensitivity was 94.3%. Testing involved sera from 149 healthy blood donors who donated 3 years previously, 400 healthy blood donors who donated during the SARS epidemic, and 131 pediatric inpatients without pneumonia. The results showed a positive test in 3/400 healthy blood donors and 1/131 pediatric patients without pneumonia. All 4 were confirmed by 2 western-blot assays. These results indicate infection with SARS-CoV in 3/400 (0.8%) healthy blood donors during the epidemic and 1/131 (0.8%) pediatric patients hospitalized without pneumonia. The researchers conclude that SARS pneumonia occurred in 1728 patients out of 7 million persons in Hong Kong, China, for an attack rate of 0.025%; the rate of nonpneumonic SARS-CoV infection was about 0.48%. A review of the 4 cases indicated that 3 were asymptomatic healthy blood donors, and the pediatric patient was hospitalized with a brief, self-limited fever.
Comment: The conclusion is that asymptomatic infection with SARS-CoV may be 10-20 times more frequent than SARS as classically described.
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