In This Edition
- Treat with antibiotics for seven days or less in adults with community-acquired pneumonia.
- In patients with chronic kidney disease who present with non ST-segment elevation acute coronary syndromes, anticoagulation with fondaparinux (Arixtra) is safer than with enoxaparin (Lovenox).
- Multislice coronary angiography rules out suspected coronary artery disease.
- Hospitalists in teaching hospitals decrease length of stay in complex patients.
- Epoetin alfa (Procrit/Epogen) use in critically ill patients does not reduce red-cell transfusion but may reduce mortality in trauma.
- Newer antibiotics appear to be more effective for acute exacerbations of chronic bronchitis.
- Low-income patients and patients seen by specialists are less likely to use generic medications.
- Hospitalist-orthopedic comanagement of patients with hip fractures does not negatively affect long-term mortality.
- Probiotics reduce antibiotic and C. difficile-associated diarrhea.
- Healthcare-associated pneumonia closely resembles nosocomial pneumonia.
Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality, but there is little consensus on the appropriate duration of antibiotic therapy. Current guidelines recommend antibiotic regimens lasting from five to 14 days. Shorter courses of antibiotic therapy may improve patient compliance, reduce risk of medication related adverse effects, and minimize the risk of antimicrobial resistance.
Study design: Meta-analysis.
Synopsis: Authors included 15 randomized controlled trials from 1990 through 2004. They compared the efficacy of short-course (seven days or less) antibiotic monotherapy versus extended regimens (longer than seven days) in patients age 12 or older with mild to moderate CAP. They excluded trials with a significant number of patients with bronchitis, healthcare-associated pneumonias, and chronic obstructive pulmonary disease exacerbations. The primary outcome measure failed to achieve clinical improvement or cure. Secondary outcome measures included mortality, bacteriologic failure, and other adverse events.
The authors found no significant differences in the risk of clinical failure, risk of mortality, risk of bacteriologic failure, or risk of adverse events in the short-course versus extended-course antibiotic regimens. This was consistent among the four antibiotic classes in the study: beta-lactam, fluoroquinolone, ketolide, and macrolide.
Bottom line: This study found no differences between short-course and extended-course antibiotic regimens in the treatment of adults with mild to moderate CAP in regard to clinical success, mortality, bacteriologic success, and adverse events.
Citation: Li JZ, Winston LG, Moore DH, et al. Efficacy of short-course antibiotic regimens for CAP: A meta-analysis. Am J Med. 2007;120(9):783-790.
Background: Fondaparinux is a selective factor Xa inhibitor approved by the FDA for the treatment and prevention of venous thromboembolism. The Organization to Assess Strategies for Ischemic Syndromes (OASIS)-5 was a randomized, double-blind trial that demonstrated fondaparinux is similar to enoxaparin in reducing the risk of ischemic events, but substantially reduces major bleeding, long-term mortality, and morbidity.1
Study design: Subgroup analysis of a randomized, controlled trial.
Setting: Hospitals to which patients with non-ST-segment elevation acute coronary syndrome presented.
Synopsis: In a subgroup analysis of 19,979 in the OASIS-5 trial, patients were divided into quartiles based on their estimated creatinine clearance, calculated by using the Modification of Diet in Renal Disease formula.2 Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately, and as a composite end point at nine, 30, and 180 days.
At nine days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90, 95% confidence interval [CI], 0.73 to 1.11); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42, CI, 0.32 to 0.56). Statistically significant differences in major bleeding persisted at 30 and 180 days.
While there was a trend toward a reduction in the composite end point among all quartiles of glomerular filtration rate (GFR), the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2. The authors concluded that the absolute differences in favor of fondaparinux (efficacy and safety) were most apparent in patients with a GFR less than 58 mL/min per 1.73 m2 and were largely the result in a reduction in bleeding events.
The subgroup analysis was not planned before the OASIS-5 data were collected, and the results have not been confirmed elsewhere. For patients managed with an early invasive strategy, catheter thrombosis occurred more often in those who received fondaparinux than enoxaparin alone. Fondaparinux is not FDA approved for this indication.
Bottom line: In patients with chronic kidney disease who present with non ST-segment elevation acute coronary syndromes, anticoagulation with fondaparinux is associated with a significant reduction in the incidence of major bleeding as compared with enoxaparin.
- Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006;354(14):1464-1476.
- Fox KA, Bassand JP, Mehta SR, et al. Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non ST-segment elevation acute coronary syndromes. Ann Intern Med. 2007;147(5):304-310.
What’s the Prognosis of Asymptomatic Patients with Suspected Coronary Artery Disease with Normal Multislice Angiogram?
Background: Several studies have demonstrated high sensitivity and negative predictive values for computed tomography (CT) coronary angiography.
Study design: Prospective, sequentially enrolled subjects.
Synopsis: A CT angiogram was given to 182 consecutive patients scheduled for conventional coronary angiography without acute coronary syndrome and insufficient coronary calcification to limit CT angiography. Researchers enrolled 141 because CT angiography was inconclusive or warranted actual conventional angiography.
These normal CT angiogram subjects were followed for a mean time of 14.7 months without loss to follow-up or any mortality. Five subsequently underwent conventional angiography eight to 11 months following CT, and three had clinically significant single-vessel disease. The other two had normal conventional angiograms. There was one myocardial infarction patient who, upon further review of CT, had previously unappreciated right-coronary-artery (RCA) disease. This prospective study demonstrated a 97.2% negative predictive value consistent with previous studies. Mortality, myocardial infarction, and subsequently identified coronary artery disease (CAD) are also consistent with previously published data for conventional angiography.
Bottom line: In this small, prospective study, multislice CT coronary angiography safely rules out suspected CAD.
Citation: Gilard M, Le Gal G, Cornily JC, et al. Midterm prognosis of patients with suspected coronary artery disease and normal multislice computer tomographic findings. Arch Intern Med. 2007;165(15):1687-1689.
Background: Two prior studies demonstrated that the use of epoetin reduced the number of red-cell transfusions in ICU patients without any other clinical benefits. There were possible subgroup differences between trauma and nontrauma patients. This study assessed a reduced dose of epoetin alfa and evaluated clinical outcomes and subgroup differences suggested by the previous studies.
Study design: Prospective, randomized, double-blind, placebo-controlled clinical trial.
Setting: 115 medical centers.
Synopsis: The study group of 1,460 patients underwent stratified randomization into trauma, surgical nontrauma, and medical nontrauma groups. There were no significant differences in transfusion requirements between the epoetin group, the placebo group, or in any subgroup. The mean pre-transfusion hemoglobin was the same in each group.
The epoetin group had a higher-than-baseline hemoglobin level at day 29 (1.6 versus 1.2 g/dL, p<0.001) and a higher absolute hemoglobin (11.2 versus 10.8 g/dL, p<0.001) than the placebo group. Mortality was lower in the epoetin group (8.5% versus 11.4%, p=0.02) and in the trauma subgroup (3.5% versus 6.6%, p=0.04). In two nontrauma groups, point estimates demonstrated similar lower mortality but were not statistically significant.
Thrombotic vascular events were higher in the epoetin group than the placebo group (16.5% versus 11.5%, p=0.008), but post-hoc analyses demonstrated that the effect was only observed in patients who had not received heparin at baseline. There were no other observed differences in length of stay or use of mechanical ventilation.
Bottom line: Epoetin alfa does not reduce red blood cell transfusions in ICU patients but may reduce mortality in trauma patients. Increased thrombotic events may be mitigated with the use of heparin.
Citation: Corwin HL, Gettinger A, Fabian TC, et al. Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med. 2007;357 (10):965-976.
Background: Hospitalists increasingly serve as teaching attending physicians at many academic medical centers. Studies have shown hospitalists’ care can reduce the length of hospital stay in patients with a limited number of specific diagnoses. It has not been established whether there are other specific patient diagnoses or discharge dispositions that might benefit from hospitalist care in a teaching hospital.
Study design: Retrospective cohort.
Setting: Urban teaching hospital.
Synopsis: The authors examined the patients discharged from a hospitalist and a non-hospitalist teaching attending service at an academic medical center during a two-year period beginning July 1, 2002. The length of hospital stay for patients on the hospitalist teaching attending service was significantly lower than that of the non-hospitalist teaching attending service. This difference was most pronounced in patients with highest overall acuity as measured by diagnosis-related group (DRG) weight and patients who required discharge to nursing facilities.
Bottom line: Medically complex inpatients and inpatients with complex discharge planning needs appear to have a shorter length of hospital stay when under the care of hospitalists serving as teaching attending physicians compared with non-hospitalist teaching attending physicians.
Citation: Southern WN, Berger MA, Bellin EY, et al. Hospitalist care and length of stay in patients requiring complex discharge planning and close clinical monitoring. Arch Intern Med. 2007;167(17):1869-1874.
Background: Expenditures for prescription medications exceeded $250 billion in 2005. Various patient, physician, and payment factors may increase generic drug use in an attempt to reduce costs without affecting quality of care.
Study design: Observational analysis.
Synopsis: This study analyzed initial and subsequent pharmacy claims for 5,399 patients enrolled in a large health plan in the western United States, from 2001-2003. For new prescriptions, 23% were generics. Initiation of generic medications was less likely for patients in poor neighborhoods and for prescriptions written by specialists; pharmacy benefit design and pharmacy type did not have a significant influence.
After initiation of branded medications, 15% switched to generics during the study follow-up. Patients were more likely to switch to generic medications if they were older, if they used mail-order pharmacies, or if they participated in multitier (three or more) co-payment plans.
Bottom line: Low-income patients and patients who see specialists are less likely to initiate generic medications; after initiation on branded medications, patients using mail-order pharmacies or multitier co-payment systems are more likely to switch to generics.
Citation: Shrank WH, Stedman M, Ettner SL, et al. Patient, physician, pharmacy, and pharmacy benefit design factors related to generic medication use. J Gen Intern Med. 2007; 22:1298-1304.
Background: Prior studies have demonstrated that for patients with hip fracture, a hospitalist-orthopedic comanagement management service reduced time to surgery and length of stay, with no difference in inpatient mortality. This study sought to address whether this applied to long-term mortality as well.
Study design: Retrospective cohort study.
Setting: Tertiary care center.
Synopsis: This study examined 466 patients admitted consecutively to a tertiary care center for surgical repair of a hip fracture, and followed them for one year postoperatively. It compared outcomes for patients admitted to a hospitalist-orthopedic comanagement service (2001-2002) with a standard care group of historical controls admitted to either an orthopedic or general medical teaching service (2000-2001).
One-year survival did not differ between the patients on the hospitalist-orthopedic comanagement service (70.5%) versus those in the standard care group (70.6%). The hospitalist-orthopedic comanagement model was associated with shorter time to surgery and shorter length of stay (8.4 versus 10.6 days). According to multivariate analysis, independent predictors of mortality were: American Society of Anesthesiologists (ASA) class III or IV (hazard ratio 4.2, 95% CI, 2.21, 7.99), admission from a nursing home (hazard ratio 2.24, 95% CI, 1.73, 2.90), and inpatient complications such as renal failure, myocardial infarction, or ICU admission (hazard ratio 1.85, CI 95%, 1.45, 2.35).
The authors note that prior studies demonstrated benefits from hospitalist involvement only after one year of implementation. This study was performed during the first year of the hospitalist-orthopedic comanagement team.
Bottom line: Hospitalist-orthopedic comanagement of patients with hip fracture reduces length of stay and does not negatively affect long-term mortality.
Citation: Batsis JA, Phy MP, Melton LJ, et al. Effects of a hospitalist care model on mortality of elderly patients with hip fractures. J Hosp Med. 2007;2:219-225.
Background: Antibiotics are frequently used for treatment of acute exacerbations of chronic bronchitis (AECB). However, in this era of increasing microbial resistance, there are insufficient data comparing the efficacy and safety of first-line antibiotics (ampicillin, amoxicillin, doxycycline, trimethoprim-sulfamethoxazole [Bactrim, Cotrima, Septra]) with second-line antibiotics (amoxicillin-clavulanic acid [Augmentin], macrolides, second- and third-generation cephalosporins, and fluoroquinolones).
Study design: Meta-analysis of randomized controlled trials (RCT).
Synopsis: Authors included 12 RCTs from 1981 to 2000, enrolling 2,261 adult patients comparing the efficacy and toxicity of first-line with second-line antibiotics for AECB in inpatient and outpatient settings. The authors measured treatment success, drug-related adverse events, all-cause mortality and pathogen eradication.
They concluded that administration of first-line antibiotics was associated with lower treatment success than administration of second-line antibiotics (odd ratio [OR] 0.51, 95% CI, 0.34 to 0.75). However, no differences were found with regard to all-cause mortality (OR 0.64, 95% CI, 0.25 to 3.35), adverse effects (OR 0.75, 95% CI, 0.39 to 1.45), or treatment success in microbiologically evaluable patients (OR 0.56, 95% CI, 0.22 to 1.43). Some limitations of this meta-analysis include:
- Inadequate data to stratify patients according to risk factors for poor outcome;
- Trials included inpatients as well as outpatients (likely with varying disease severity); and
- Trials were conducted in different time periods with changing patterns of anti-microbial resistance.
Bottom line: In patients with AECB, second-line antibiotics are more effective than first-line antibiotics with no differences in safety or mortality.
Citation: Dimopoulos G, Siempos II, Korbila IP, et al. Comparison of first-line with second-line antibiotics for acute exacerbations of chronic bronchitis. Chest. 2007;132:447-455.
Background: Patients on antibiotics experience diarrhea as a side effect 5%-25% of the time, of which C. difficile is the cause in 15%-25% of these cases. Probiotics, such as Streptococcus thermophilus, Enterococcus species, Saccharomyces species, and Lactobacillus species are live microorganisms that can safely be used to treat diarrhea associated with antibiotic use.
Study design: Randomized, double-blind, placebo controlled
Setting: Three London hospitals
Synopsis: The study enrolled 135 hospitalized patients over age 50 who were prescribed antibiotics.
The treatment group received a probiotic yogurt drink containing Lactobacillus casei, L. bulgaricus, and S. thermophilus; the placebo group received a sterile milkshake. Subjects consumed the drinks twice daily within 48 hours of starting antibiotic therapy and continued for one week after antibiotic use.
There was a significant reduction of diarrhea in the probiotic group (p=0.007); the number needed to treat (NNT) was five. There was also a significant decrease in diarrhea caused by C. difficile (p=0.001), the secondary outcome, with an NNT of six.
These results may translate into decreased patient morbidity, mortality, healthcare costs, and length of stay. Additional studies are needed to establish the most effective probiotic and dosing for reducing diarrhea.
Bottom line: Twice-daily consumption of probiotic drinks can decrease the risk of antibiotic-induced diarrhea.
Citation: Hickson M, D’Souza AL, Muthu N, et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomized double blind placebo controlled trial. BMJ. 2007 Jul 14;335(7610):80.
Background: Changes in practice patterns have resulted in a large number of patients who regularly interact with healthcare but aren’t admitted to the hospital (e.g., those receiving dialysis or home healthcare). These patients develop nosocomial-type infections rather than infections from traditionally community-acquired organisms.
Study design: Prospective observational for three years.
Setting: A large teaching hospital in Barcelona, Spain.
Synopsis: A total of 727 patients were stratified into community-acquired pneumonia (CAP) or healthcare-associated pneumonia (HCAP) groups based on whether they had:
- Received home intravenous therapy;
- Attended a hospital or hemodialysis clinic or had chemotherapy in the preceding 30 days;
- Were admitted to an acute care facility for at least two days in the preceding 90 days; or
- Resided in a nursing home.
The HCAP group tended to be older, have higher comorbidities (particularly cerebrovascular disease or malignancy), have previously received antibiotics, and have higher pneumonia severity indices.
The putative organisms were similar in both groups with Streptococcus pneumoniae representing the most common pathogen. HCAP patients had higher rates of penicillin, erythromycin, and levofloxacin resistance; aspiration pneumonia; longer lengths of stay; and 30-day mortality. Inappropriate therapy occurred more commonly in the HCAP group (5.6% versus 2.0%). Such therapy was defined as the absence of antibiotics targeting suspect pathogens, the use of antibiotics to which the bacteria were not susceptible, or the failure to start anaerobic coverage for aspiration pneumonia.
Bottom line: Outpatients who come in frequent contact with the healthcare system while presenting with pneumonia are more likely to have drug-resistant organisms similar to those seen in nosocomial pneumonia. Further, they tend to have inappropriate or inadequate antimicrobial therapy, longer hospital stays, and increased risk of death.
Citation: Carratalà J, Mykietiuk A, Fernández-Sabe N, et al. Health care-associated pneumonia requiring hospital admission. Arch Intern Med. 2007;167(13):1393-1399. TH