Monday, October 23, 2006

Lit Bits: October 23, 2006

From the recent medical literature...

1. Guideline-Recommended Antibiotics Reduce Early Pneumonia Mortality

For patients hospitalized with community-acquired pneumonia, early mortality is reduced if they receive antibiotics recommended by current guidelines, according to two retrospective cohort studies from related research groups.The first study examined data from 787 patients (79% men). After adjustment for numerous factors (including pneumonia severity and antibiotic treatment within 4 hours), initiation of current guideline-recommended antibiotic therapy within 48 hours of admission reduced by about two-thirds the risk for death in those first 48 hours, compared with other antibiotic regimens. The authors say that their study "calls into question the concept that mortality within the first 48 to 96 hours after admission is not modifiable."

In the second study, partially funded by manufacturers, in-hospital mortality was 3% when recommended therapy began within 24 hours of admission versus 7% with other antibiotics -- a 57% relative risk reduction. In addition, guideline-concordant therapy was associated with shorter hospital stays and decreased time to switch to oral therapy.

Both studies appear in the October American Journal of Medicine (vol 199).

Study #1 (Free abstract; full text requires subscription):

Study #2 (Free abstract; full text requires subscription):

2. Travel-Related Venous Thrombosis: Traveling for 4 hours or more within the prior 8 weeks doubles your risk

Suzanne C. Cannegieter, et al. PLoS Medicine (Public Library of Science), a peer-reviewed, open-access journal

Background: Recent studies have indicated an increased risk of venous thrombosis after air travel. Nevertheless, questions on the magnitude of risk, the underlying mechanism, and modifying factors remain unanswered.

Methods and Findings: We studied the effect of various modes and duration of travel on the risk of venous thrombosis in a large ongoing case-control study on risk factors for venous thrombosis in an unselected population (MEGA study). We also assessed the combined effect of travel and prothrombotic mutations, body mass index, height, and oral contraceptive use. Since March 1999, consecutive patients younger than 70 y with a first venous thrombosis have been invited to participate in the study, with their partners serving as matched control individuals. Information has been collected on acquired and genetic risk factors for venous thrombosis.

Of 1,906 patients, 233 had traveled for more than 4 h in the 8 wk preceding the event. Traveling in general was found to increase the risk of venous thrombosis 2-fold (odds ratio [OR] 2.1; 95% confidence interval [CI] 1.5-3.0). The risk of flying was similar to the risks of traveling by car, bus, or train. The risk was highest in the first week after traveling.

Travel by car, bus, or train led to a high relative risk of thrombosis in individuals with factor V Leiden (OR 8.1; 95% CI 2.7-24.7), in those who had a body mass index of more than 30 kg/m2 (OR 9.9; 95% CI 3.6-27.6), in those who were more than 1.90 m tall (OR 4.7; 95% CI 1.4-15.4), and in those who used oral contraceptives (estimated OR > 20). For air travel these synergistic findings were more apparent, while people shorter than 1.60 m had an increased risk of thrombosis after air travel (OR 4.9; 95% CI 0.9-25.6) as well.

Conclusions: The risk of venous thrombosis after travel is moderately increased for all modes of travel. Subgroups exist in which the risk is highly increased.


3. Psoriasis May Be an Independent Risk Factor for MI

Psoriasis was linked with increased risk for myocardial infarction, especially in younger patients, in a prospective cohort study published in an October issue of JAMA. Researchers in the U.K. identified more than 130,000 patients (aged 20 to 90) with psoriasis, matched each one with up to five controls, and followed them for an average of about five and a half years.

Patients with psoriasis had a higher risk for MI than controls, and patients with severe psoriasis had a higher risk than those with mild psoriasis. The association was more pronounced in younger patients. A 30-year-old patient with severe psoriasis had a relative risk for MI of 3.10 compared with controls, for example, whereas the relative risk was 1.36 for a 60-year-old. The incidence of MI was low, however, occurring in about 2% of controls and about 3% of patients with severe psoriasis.

JAMA article (free):

4. Pediatrics Academy Stresses Benefits of Playtime

A report of the American Academy of Pediatrics urges pediatricians to recommend that children be given ample time for play that is "child driven rather than adult directed." The report notes the trend toward pushing children to take part in organized after-school activities. It says that while these can be helpful for many youngsters, there is also a risk of leaving too little time for creative play.

It says healthcare providers should:

  • recommend that children get "ample, unscheduled, independent, nonscreen time to be creative, to reflect and to decompress";
  • discourage parents from offering computer games and other passive entertainment and instead emphasize active play;
  • promote the benefits of toys like blocks and dolls that allow children to use their imaginations;
  • reassure parents regarding the value of unscheduled time with their children and remind them that their love, role modeling, and guidance are more important to success than extracurricular commitments.
AAP committee report (Free PDF):

5. Two Studies on Treating Symptomatic Carotid Disease

Lancet: A comparison of two treatments for symptomatic carotid stenosis -- angioplasty with stenting versus endarterectomy -- failed to show that stenting is no worse than endarterectomy.

In SPACE -- a large study conducted in Germany, Austria, and Switzerland -- researchers randomized some 1200 patients to stenting or endarterectomy. Analyzing the results at 30 days after the procedure, the researchers found that although there was only a small absolute difference in the rate of death or ipsilateral ischemic stroke (0.51% higher in the stenting group), there was no statistical proof of the non-inferiority of stenting.

The author of a commentary that accompanies the article in the current Lancet quips that the study "has provided surgeons and interventionists with evidence to support their personal prejudices." He adds that to date, "no systematic evidence exists to support the preferential use of carotid endarterectomy over carotid angioplasty and stenting or vice versa."

Lancet article (Free abstract; full text requires subscription):

NEJM: To compare treatments for carotid stenosis, researchers in the EVA-3S trial measured rates of stroke or death in patients with severe symptomatic disease who were randomized to either stenting or endarterectomy.

The trial included more than 500 patients, and, like the SPACE trial published earlier this month in the Lancet, it was unable to show the non-inferiority of stenting in the comparison. EVA-3S was stopped early when the rate of stroke or death at 30 days was found to be higher in the stenting group (9.6%) than the endarterectomy group (3.9%). The study appears in a recent New England Journal of Medicine.

An editorialist concludes that "the only widely accepted indication for carotid-artery stenting remains its use in symptomatic patients who have stenosis of the internal carotid artery exceeding 70% and who also have a high surgical risk."


6. One in eight ECGs from MI patients are misinterpreted in the ED, data suggest

from Heartwire--a professional news service of WebMD
[This is a discussion of an abstract from a Kaiser study featured in the last issue of Lit Bits.]

Steve Stiles. October 6, 2006 (Dallas, TX). Emergency department (ED) personnel failed to identify important, high-risk features on the electrocardiograms of about one in eight patients presenting with an acute MI in a retrospective analysis based on the two-year experience of five medical centers.

The ECG misinterpretations, which often kept the patients from receiving appropriate, evidenced-based treatments, were especially common among patients without chest pain at presentation, "suggesting that the absence of typical historical findings may inordinately reduce clinicians' level of suspicion for acute MI," write the authors, Dr Frederick A Masoudi (University of Colorado at Denver and Health Sciences Center) and colleagues.

Their analysis suggests that misinterpreted ECGs are "relatively common" in the ED and "a critical shortfall in the process of caring for patients with acute MI, with important implications for treatment and potential adverse consequences for patient outcomes," according to the investigators from the retrospective, cohort-based Emergency Department Quality in Myocardial Infarction (EDQMI) study. Their report was published online October 2, 2006 in Circulation and is scheduled to appear in the journal's October 10 issue.

"To be honest, the results of the study don't surprise me that much," Dr Charles V Pollack Jr (Pennsylvania Hospital, Philadelphia) told heartwire. "I think this is a legitimate problem that hasn't been addressed in the past." He pointed out, however, that the analysis was limited to a handful of centers and so doesn't necessarily apply to emergency departments in general--something the authors acknowledge in their report. Pollack chairs the department of emergency medicine at his center and is an investigator with the CRUSADE registry of patients with non-ST-elevation acute coronary syndromes.

Although it's "conceivable" that some ED physicians would use less care in reading the ECG of a patient with an atypical presentation, he said, more of a problem are patients with presentations "so atypical we may not even get an electrocardiogram." Such patients are often women, the elderly, diabetics, or those with heart failure, he observed.

Of 1684 patients with acute MI presenting to the ED at five centers in California and Colorado, all members of health-maintenance organizations, about 12% had a high-risk ECG abnormality such as T-wave inversion or an ST-segment shift that wasn't spotted by ED care providers. Patients with left-bundle branch block had been excluded from the analysis.

After controlling for institution and patient characteristics, according to Masoudi et al, researchers determined that the likelihood of a missed high-risk ECG abnormality was increased by 78% (p=0.005) among patients with heart failure and by 44% (p=0.03) among those with any history of CV disease, and it was reduced by 54% (p<0.001).

7. Drugs to Curb Agitation Are Said to Be Ineffective for Alzheimer's

The benefits of using second-generation antipsychotic drugs to treat psychosis, aggression, and agitation in patients with Alzheimer disease may be offset by the drugs' adverse effects, according to a study in an October issue of New England Journal of Medicine.

In the double-blind, placebo-controlled trial, 421 patients were randomized to treatment with olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), or placebo. There were no significant differences in the time to discontinuation of treatment for any reason, including drug intolerability, among the four groups. In addition, improvement measures were not significantly different compared with placebo. The authors concluded that the drugs' adverse effects offset the advantages of their use in these patients.

Commenting in Journal Watch, editor-in-chief Allan S. Brett writes: "Although these findings do not invalidate therapeutic trials of these drugs in appropriately selected patients with Alzheimer disease, they do suggest that clinicians should think twice before treating such patients with antipsychotic drugs."

NEJM (abstract):

Washington Post article:

8. No evidence yet for ultralow LDL-cholesterol levels, according to Michigan researchers

from Heartwire--a professional news service of WebMD. Michael O'Riordan. October 12, 2006 (Ann Arbor, MI) - A new review published in the October 3, 2006 issue of the Annals of Internal Medicine argues that while there is compelling evidence supporting moderate to high-dose statin therapy in patients at high cardiovascular risk, there is no clinical evidence supporting the recommended treatment target of ultralow LDL-cholesterol levels, such as the proposed <70.

9. Physical Fitness Contributes to Successful Mental Aging

News Author: Marlene Busko. October 12, 2006. A Scottish study found that 79-year-old individuals who were more physically fit had greater mental acuity, even after accounting for childhood IQ.

Lead author Ian J. Deary, PhD, at the University of Edinburgh in Edinburgh, Scotland, told Medscape, "We found that fitness did contribute a small amount to cognitive ability in old age. What is new here is that we had people aged 79, and we knew their cognitive ability at age 11. Therefore, we were able to rule out the possibility that smarter people in youth get fitter in old age." The article is published in the October 10 issue of Neurology.

Same IQ Test at Age 11 and 79 Years

Dr. Deary and colleagues explained that studies have shown that better physical fitness in middle and old age is associated with higher cognitive test scores, but it was unclear if a causal relationship exists between these variables or if later fitness was decided by childhood IQ. The team sought to determine whether physical fitness contributes to successful cognitive aging over and above cognitive ability in youth.

The authors recruited healthy individuals who were 79 years old and living in the community in Lothian, Scotland. The study subjects had participated in the Scottish Mental Survey of 1932, which had measured the IQ of all children in Scotland who were born in 1921.

A retrospective cohort of 460 individuals (272 women and 188 men, with a mean age of 79.1 +/- 0.6 years) met the study criteria. Study requirements included having Moray House Test score data (showing general mental ability) from age 11 and 79 years, no history of dementia, a normal Mini-Mental State Examination (MMSE) score, successful APOE genotyping, and full information on smoking, social class, and education. The researchers derived a latent measure of physical fitness from 3 measures at age 79 years: the time it took to walk 6 m at a normal pace, the best of 3 trials of grip strength, and the best of 3 trials of forced expiratory volume of air from the lungs in 1 second (FEV1). These physical fitness indicators were adjusted for sex and height.

A Sound Mind in a Sound Body

The team found that physical fitness contributed more than 3% of the variance in the study participants' cognitive ability at age 79 years, after adjusting for their cognitive test scores at age 11 years. "Having this rare early baseline we can rule out the possibility in the present study that intelligence measured in early life is causal to general fitness in old age," the group writes. In addition, participants with a high IQ as a child were more likely to have better lung function (FEV1), but not better grip strength or ability to walk, at age 79 years. This "remarkable result" rules out the possibility that performance of these physical tests in old age reflects the physical ability they had as children, the investigators add.

"The important result here is that fitness, extracted as a latent trait from the three indicators, contributed to later life cognition after adjusting for childhood IQ," Dr. Deary and colleagues write. This implies that of 2 people starting with the same IQ at age 11 years, the fitter person at age 79 years will, on average, have better cognitive function (after adjusting for social class, APOE- 4 status, sex, and height), they add, noting that the findings apply only to healthy aging. "At the level of the general population, being fit is not only good in itself, it is also associated with better cognitive functioning," Dr. Deary told Medscape. "For a clinician, surely this just reinforces the message that it is a good thing to be as physically fit as one can be." The study was funded by the United Kingdom's Biotechnology and Biological Sciences Research Council.

Neurology. 2006;67:1195-1200.

10. Hospitals Urged to Ease Mobile Phone Rules

LONDON (Reuters) Oct 13 - Patients and medical staff should be allowed to use mobile phones more freely in hospitals because the benefits outweigh the risks, researchers said on Friday. There is no evidence that using them has serious consequences for patients, according to Stuart Derbyshire, a senior lecturer in psychology at the University of Birmingham, and Adam Burgess, senior lecturer in sociology at the University of Kent.

Writing in the British Medical Journal, they said restrictions were likely to become even tighter, with a Department of Health recommendation that camera-phones should not be allowed in patient areas, to protect privacy.
The biggest concern is that mobiles interfere with sensitive medical equipment. But a 1997 study from the UK's Medical Devices Agency showed that phones affected just 4% of devices at a distance of one metre, the researchers said.

Phones could adversely affect pacemakers "but only when the patient holds their phone against the chest rather than the ear, and the effects stop once the phone is removed," the authors said. In general, the interference was merely an irritation and ultimately harmless to the patient, they added.

"Sensible caution regarding the proximity of mobile phones to medical equipment is thus warranted, but concerns about patient safety alone do not justify zealously enforced no-phone areas, which can cause arguments between staff, patients and visitors."

Phones may also be annoying, but no more so than televisions or stereos, they said. "Doctors and pharmacists would benefit from using mobile phones rather than pagers, and many patients in hospital would welcome the opportunity to relieve their isolation without resorting to expensive hospital phones that are cumbersome to use," the researchers said.

11. Diverticulitis Increasingly Diagnosed in Young, Obese Individuals

News Author: Karla Gale. October 13, 2006. The demographics of acute diverticulitis are changing, according to results of a new study.
Even though most medical textbooks suggest that acute diverticulitis is primarily confined to elderly patients, radiologists in Baltimore report that the majority of cases treated recently at their institution's emergency department occurred in patients age 50 and younger.

Approximately one in five cases was diagnosed in patients below the age of 40. "I've been doing abdominal and pelvic CT scans for about 12 years, and during the last 5 years, I was seeing a lot more acute diverticulitis cases in young patients who were obese," Dr. Barry Daly said in an interview with Reuters Health.

To confirm this observation, Dr. Daly and Dr. Eram Zaidi reviewed medical records of 104 adult patients treated at the University of Maryland Medical Center for acute diverticulitis between 1999 and 2003. Their findings appear in the American Journal of Roentgenology for September.

The age of their cohort ranged from 22 to 88 years (median 49.0). The authors observed that 53.8% of patients were no older than 50, and 21.1% were age 40 and younger. Drs. Daly and Zaidi documented abdominal obesity in 82% of subjects, as determined by a sagittal abdominal diameter of > 25 cm. Patients no older than 50 were more likely to be obese than older patients (p = 0.05). The differential was more pronounced when limiting the analysis to patients aged 40 years or less and those over 70 years (27.7 cm versus 24.9 cm, p = 0.02).

Eighty-nine percent of patients required hospital admission, the investigators report. CT scans revealed complications in 36% of patients, including colon perforation, abscess, fistula formation, and stricture formation or bowel obstruction. Surgery or percutaneous abscess drainage was required by 26.9%.

In their report, the investigators emphasize the importance of CT imaging in determining or confirming a diagnosis of acute diverticulitis, accurate staging of the inflammatory response, identifying serious complications, and guiding clinical management of patients.

Failure to accurately diagnose acute diverticulitis in younger individuals early in the disease process increases the risk of major complication. Moreover, because of their longer remaining lifespan, "young adults are at risk for repeated episodes," Dr. Daly added. "We've seen patients with up to five acute attacks, and we have patients who had three surgeries."

"Acute diverticulitis is not a trivial disease," he emphasized. Acute diverticulitis is associated with fever, malaise, elevated white cell count and other clinical factors, characteristics that should guide physicians when considering referral for a CT scan.

Dr. Daly pointed out that some patients do develop a mild, self-limiting case of diverticulitis involving inflammation of a single diverticulum. "But typically, those who present at the ED have extensive disease, and quite a few of them are going to develop complications," he added. In young adults with belly pain, he recommends that acute diverticulitis be included in the differential diagnosis, along with appendicitis, acute colicystitis, acute pancreatitis, and colitis.Am J Roentgenol. 2006;187:689-694.

12. Adverse Drug Events Often Lead to ED Visits

Some 700,000 people go to emergency rooms in the U.S. annually because of adverse events involving therapeutic drugs, government researchers estimate. A nationally representative sampling of 63 hospitals over a two-year period found that:

  • Patients 65 or older accounted for one quarter of such visits and almost half of the visits requiring hospitalization.
  • One third of the visits were occasioned by allergic reactions and another third by unintentional overdoses.
  • About 40% of the visits were attributable to the use of CNS agents (especially opioid-containing analgesics) and systemic antimicrobials (especially amoxicillin).
The report, written by members of the CDC, FDA, and the Consumer Product Safety Commission, appears in JAMA.


13. Sitagliptin, First in New Class of Diabetes Drugs, Approved

The FDA this week approved the type 2 diabetes treatment Januvia (sitagliptin). It's the first drug approved in a new class known as dipeptidyl peptidase 4 (DPP-4) inhibitors.

Januvia's mechanism is glucose-dependent, according to the manufacturer, lowering the potential for hypoglycemia. It and other DPP-4 inhibitors under development work by blocking the breakdown of proteins that stimulate insulin synthesis and release when blood glucose rises. In clinical trials, use of the drug was not associated with either hypoglycemia or weight gain, and the drug lowered A1C levels by roughly 0.7%.

Januvia has been approved as a monotherapy adjunct to diet and exercise or for use in combination with metformin or thiazolidinediones. The drug will cost $4.86 per daily tablet, according to the manufacturer.

Asked to comment, Dr. Merri L. Pendergrass, director of clinical diabetes at Boston's Brigham and Women's Hospital, said "Januvia will add to the growing list of treatment options for type 2 diabetes. However, at least in the near future, the relatively high cost and lack of long-term safety data for DPP4 inhibitors will likely keep Januvia well down on the list of preferred treatments."

FDA Press Release:

14. GERD Symptoms Increase the Rate of COPD Exacerbations

News Author: Laurie Barclay, MD. October 17, 2006. The rate of chronic obstructive pulmonary disease (COPD) exacerbations in patients with gastroesophageal reflux (GERD) symptoms is twice as high as in those without GERD symptoms, according to the results of a cross-sectional survey published in the October issue of Chest.

"Microaspiration of gastric contents and/or vagal irritation from GER [gastroesophageal reflux] may constitute airway irritants and thus represent a potential pathogenic mechanism for acute exacerbations of COPD," write Ivan E. Rascon-Aguilar, MD, from the University of Florida Health Science Center in Jacksonville, and colleagues. "The impact of gastroesophageal reflux disease (GERD) on exacerbations of COPD has never been evaluated. The aims of this investigation were to determine the prevalence of gastroesophageal reflux (GER) symptoms in COPD patients and the effect of GER on the rate of exacerbations of COPD per year."

For this questionnaire-based, cross-sectional survey, 86 patients with an established diagnosis of COPD were recruited from outpatient pulmonary clinics and interviewed in person or by telephone. Patients with respiratory disorders other than COPD, known esophageal disease, active peptic ulcer disease, Zollinger-Ellison syndrome, mastocytosis, scleroderma, and current alcohol abuse were excluded. Clinically significant reflux was defined as weekly episodes of heartburn and/or acid regurgitation. Other endpoints were frequency and type of COPD exacerbations.

Mean patient age was 67.5 years, 55% were men, and 37% reported GERD symptoms. The mean forced expiratory volume in 1 second (FEV1) percentage of predicted was similar in patients with or without GERD, but the rate of COPD exacerbations was twice as high in patients with GERD symptoms as in those without GERD symptoms (3.2 per year vs 1.6 per year; P = .02).

"The presence of GER symptoms appears to be associated with increased exacerbations of COPD," the authors write. "We also conclude that COPD patients with weekly GER symptoms and COPD are twice as likely to be hospitalized, have an ED visit, or unscheduled clinic visit when compared with COPD patients with less frequent GER symptoms."

Study limitations include inability to conclude whether the use of antireflux therapy was protective against exacerbations, inability to establish a cause-and-effect association from the cross-sectional data, possible recall bias, and limited sample size.

"The findings of this study suggest a possible modifiable risk factor in exacerbations of COPD," the authors conclude. "The implications of this link may not only be of clinical significance but also of economic significance, considering the cost of a single hospitalization, and taking into account that in the year 2000 there were 726,000 hospitalizations, 1.5 million ED visits, and 8 million office visits all due to exacerbations of COPD." The authors have disclosed no relevant financial relationships.

Chest. 2006;130:1096-1101.

15. A prospective, randomized clinical investigation of the treatment of first-time ankle sprains.

Am J Sports Med. 2006; 34(9):1401-12. Beynnon BD, et al.

BACKGROUND: Acute ankle ligament sprains are treated with the use of controlled mobilization with protection provided by external support (eg, functional treatment); however, there is little information regarding the best type of external support to use.

HYPOTHESIS: There is no difference between elastic wrapping, bracing, bracing combined with elastic wrapping, and casting for treatment of acute, first-time ankle ligament sprains in terms of the time a patient requires to return to normal function.

STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 1.

METHODS: Patients suffering their first ligament injury were stratified by the severity of the sprain (grades I, II, or III) and then randomized to undergo functional treatment with different types of external supports. The patients completed daily logs until they returned to normal function and were followed up at 6 months.

RESULTS: Treatment of grade I sprains with the Air-Stirrup brace combined with an elastic wrap returned subjects to normal walking and stair climbing in half the time required for those treated with the Air-Stirrup brace alone and in half the time required for those treated with an elastic wrap alone.

Treatment of grade II sprains with the Air-Stirrup brace combined with the elastic wrap allowed patients to return to normal walking and stair climbing in the shortest time interval.

Treatment of grade III sprains with the Air-Stirrup brace or a walking cast for 10 days followed by bracing returned subjects to normal walking and stair climbing in the same time intervals. The 6-month follow-up of each sprain severity group revealed no difference between the treatments for frequency of reinjury, ankle motion, and function.

CONCLUSION: Treatment of first-time grade I and II ankle ligament sprains with the Air-Stirrup brace combined with an elastic wrap provides earlier return to preinjury function compared to use of the Air-Stirrup brace alone, an elastic wrap alone, or a walking cast for 10 days.

16. IDSA/ATS to Release New Guidelines on CAP Diagnosis and Treatment

October 19, 2006 (Toronto) . For the first time, the Infectious Diseases Society of America and the American Thoracic Society have jointly released guidelines on the diagnosis and treatment of community-acquired pneumonia (CAP).
Highlights from the new guidelines were presented here at the 44th annual meeting of the Infectious Diseases Society of America and approved shortly thereafter. The ATS had already approved the new document.

These guidelines, which will appear on the IDSA Web site ( in January and are scheduled to be published in the February or March issue of Clinical Infectious Diseases, follow the joint release of guidelines from the 2 societies on the treatment of hospital-acquired pneumonia.

One of the themes of the guidelines is minimizing the "misuse and abuse of antibiotics," said Lionel Mandell, MD, FRCPC, FRCP(Lond), an infectious disease specialist and professor of medicine at McMaster University in Hamilton, Ontario, Canada, and cochair of the joint IDSA/ATS committee that drafted the guidelines.

"We don't want everyone using quinolones, which is why they are optional," Dr. Mandell told Medscape. "We want to reduce the risk of resistance. If a patient took a macrolide in the last 3 months, then we are saying not to prescribe a macrolide again. The same goes for quinolones." The authors of the guidelines recognize that some methicillin-resistant Staphylococcus aureus (MRSA) strains are increasingly being linked to CAP. These highly pathogenic MRSA strains usually have a novel type IV SCCmec gene, and many have the gene for Panton-Valentine leukocidin (PVL). The PVL cytotoxin is associated with presentation such as necrotizing pneumonia, abscess and empyema formation, respiratory failure, and shock.

In the new guidelines, pretreatment blood cultures and routine Gram staining and culture of expectorated sputum are recommended for patients with "selected clinical conditions." The 2003 guidelines suggested that all patients hospitalized for pneumonia should have 2 pretreatment blood cultures and expectorated sputum Gram staining and culture. "We aren't saying don't do cultures," Dr. Mandell said. "We are saying don't do cultures when you aren't going to get anything from it."

In the updated guidelines, clinical indications such as neutropenia, chronic severe liver disease, severe chronic obstructive lung disease, and asplenia justify more extensive diagnostic testing and suggest the need for blood cultures. If a patient is a recent traveler, has positive rapid legionella, or is positive for the pneumococcal urinary antigen test, sputum cultures are warranted.

The new guidelines support the use of the Pneumonia Severity Index (PSI) as a scoring system to determine which patients require hospital admission. They also support the use of CURB-65 (Confusion, Urea > 7 mmol/L, Respiratory rate 30/min, systolic blood pressure 90 mm Hg, and diastolic blood pressure 60 mm Hg, and age 65 years or older).

When calculating the 30-day mortality rate, if the CURB-65 score is greater or equal to 3, the site of care should be the intensive care unit (ICU). If the score is 2, admission to a hospital is sufficient. Outpatient management is warranted when the CURB-65 score is 0 or 1. Where resources are sufficient, the PSI can identify patients who can be managed on an outpatient basis. The PSI is based on mortality risk factors in patients with the disease. While not as extensively studied, the CURB-65 is a more practical tool in a busy emergency department (ED), according to Dr. Mandell. Head-to-head comparison in a clinical trial is needed to determine whether PSI or CURB-65 is superior, according to the guidelines.

The new guidelines recommend admission to an ICU if the patient suffers septic shock or requires mechanical ventilation. ICU admission is also warranted if patients have 3 of the minor criteria for severe CAP, including a respiratory rate of 30/min or more, PaO2/FIO2 250, multilobar infiltrates, confusion, uremia, neutropenia, thrombocytopenia, and hypothermia.For patients who are previously healthy and have not used antimicrobials within the previous 3 months, a macrolide or doxycycline is recommended. If comorbidities are present or antimicrobials have been used in the previous 3 months, an alternative antimicrobial from a different antibiotic class should be chosen. Specifically, if a quinolone has been prescribed in the previous 3 months, then a quinolone should not be prescribed. If a macrolide has been prescribed in the previous 3 months, then a macrolide should not be prescribed.

Treatment options include: a respiratory fluoroquinolone, including moxifloxacin, gemifloxacin, and levofloxacin (750 mg), or beta lactam and a macrolide, or telithromycin if there are no risks for enteric gram-negatives. "There have been some reports of toxicity with telithromycin," said Dr. Mandell, noting that FDA had reviewed those cases of toxicity associated with telithromycin."Our contention was that toxicity was not any worse than any other drug." However, telithromycin should not be prescribed if the patient has a history of liver dysfunction. Of note, gatifloxacin is no longer recommended as a possible therapy because of concerns regarding its adverse-event profile.
A respiratory fluoroquinolone or a beta lactam in combination with a macrolide is acceptable if the patient is not being admitted to the ICU. Patients being admitted to the ICU require a beta lactam plus azithromycin or a respiratory quinolone.

The previous guidelines stated that the window for initiation of antibiotic therapy was 4 hours from the time the patient was seen and assessed. The guidelines now give no specific timing guideline or window, because the studies that supported the previous early-treatment recommendations had internal consistency problems. The new guidelines encourage initiation of antibiotic therapy as soon as possible, with the understanding it will vary from institution to institution. When patients are admitted to the ED, the first antibiotic dose should be administered while patients are still in the ED.

Paul Auwaerter, MD, a member of the IDSA 2006 program committee and moderator of the session in which the guidelines were released, said that the absence of a recommendation on the timing of therapy is justified.
"Much of the data was observational and not from prospective studies in terms of making a strict recommendation on timing," said Dr. Auwaerter, clinical director of infectious diseases at Johns Hopkins University in Baltimore, Maryland. "Many patients may have other diagnostic considerations, so we want to allow some time to ascertain those issues before the administration of antibiotics."

The selective use of blood cultures is a step to more prudent use of antibiotics, according to Dr. Auwaerter. He added that cultures could be contaminated and not accurate indicators of disease. "Blood cultures rarely impacted the routine care of pneumonia patients that don't fit special considerations," said Dr. Auwaerter. "We may be administering unnecessary antibiotics based on early information."

Duration of treatment has been shortened to a minimum of 5 days, providing patients are afebrile for 48 to 72 hours and have no more than 1 sign of clinical instability. Extended duration is warranted if initial therapy is not effective, if there there are complications due to extrapulmonary infection such as meningitis or endocarditis, or if bacteremia is present, especially S aureus, S pneumoniae, or P aeruginosa.

Other differences between the 2003 guidelines and the 2007 guidelines are that the new guidelines contain a section on pandemic influenza, on the management of nonresponding pneumonia, but they contain no discussion sections on the elderly or bioterrorism. Dr. Mandell reports no relevant financial relationships. Dr. Auwaerter is a member of advisory boards for Schering-Plough, Pfizer, and Ortho-McNeil.

IDSA 44th Annual Meeting: Update on Practice Guidelines. Presented October 13, 2006.

17. In Acute Otitis Media, Who Benefits Most from Antibiotics?

Antibiotic treatment of acute otitis media is most beneficial for children under 2 with bilateral disease and children with both otitis and otorrhea; most others can be managed with watchful waiting, concludes a meta-analysis in this week's Lancet.

Researchers analyzed data from six randomized trials that included some 1600 participants, 6 months to 12 years old, with acute disease. For those under 2 years old with bilateral otitis, the number needed to treat (NNT) to prevent an extended course was 4; for those in that age group with unilateral otitis, it was 20. The NNT for children with otorrhea was 3.

In a departure from current U.S. guidelines, the authors conclude that watchful waiting is appropriate for children aged 6 months to 2 years with unilateral acute otitis media. The guidelines recommend observation in that age group only if the diagnosis is uncertain or if the disease is not severe.