Title:  Antibiotics for Bacteremic Pneumonia: Improved Outcomes With Macrolides but Not Fluoroquinolones. Authors:  Metersky ML, Ma A, et al:                            Journal: Chest 2007; 131 (February): 466-473
 

 MEDSCAPE News

Author: Laurie Barclay,

MD

CME Author: Charles

Vega, MD, FAAFP

A review of diagnostic and therapeutic practices for evaluating and treating adult bacterial meningitis in primary and emergency care settings is published in the March issue of Lancet Infectious Diseases.

“Despite the existence of antibiotic therapies against acute bacterial meningitis, patients with the disease continue to suffer significant morbidity and mortality in both high and low-income countries,” write Michael T. Fitch, MD, PhD, from the Wake Forest University School of Medicine in Winston-Salem, North Carolina, and colleagues. “Dilemmas exist for emergency medicine and primary-care providers who need to accurately diagnose patients with bacterial meningitis and then rapidly administer antibiotics and adjunctive therapies for this life-threatening disease. Physical examination may not perform well enough to accurately identify patients with meningitis, and traditionally described lumbar puncture results for viral and bacterial disease cannot always predict bacterial meningitis.”

The authors review current treatment guidelines for adults with suspected bacterial meningitis in the context of findings from recent studies. To increase awareness of guidelines for antibiotics and adjunctive steroids among clinicians who prescribe the initial doses of antibiotics in an emergency setting, the authors present an overview and discussion of key diagnostic and therapeutic decisions in the emergency evaluation and treatment of adults with suspected bacterial meningitis.

Although the initial steps in evaluation typically focus on history and physical examination, the available literature suggests that much of this evaluation may not accurately identify meningitis. The authors review the basis for decision making regarding neuroimaging before lumbar puncture, the interpretation of lumbar puncture results, and the empiric treatment of presumptive bacterial meningitis with antibiotics together with adjunctive systemic steroids.

To assist clinicians in their approach to patient care for this potentially life-threatening infection, the authors present a previously published algorithm for the treatment of patients with suspected community-acquired bacterial meningitis. Although signs and symptoms alone provide insufficient information to diagnose meningitis, one meta-analysis suggests that the absence of fever, neck stiffness, and altered mental status effectively eliminates meningitis as a likely diagnosis with a sensitivity of 99% to 100%.

In another study, at least 1 of 4 key elements (headache, fever, neck stiffness, and alterations in mental status) was present in 99% of patients, suggesting that aspects of history and physical examination can be used to heighten suspicion of meningitis even if they cannot alone rule out the diagnosis.

Most adults with bacterial meningitis do not present with prominent skin findings such as the rash typical of meningococcus infection (only 11% of cases in a large retrospective series and only 26% of cases in a prospective study). Kernig’s sign, Brudzinski’s sign, and meningismus also lack adequate sensitivity to be used in isolation to diagnose or exclude a potentially life-threatening disease.

Although increased intracranial pressure may result in brain herniation following lumbar puncture, several studies have shown no clinical changes in patients who had lumbar puncture to diagnose meningitis. In the opinion of the authors, it is reasonable to proceed with lumbar puncture without a computed tomographic (CT) scan if the patient does not have any of the following: new-onset seizures, an immunocompromised state, signs that are suspicious for space-occupying lesions (papilloedema or focal neurologic signs excluding cranial nerve palsy), or moderate-to-severe impairment of consciousness.

Cerebrospinal fluid findings may not accurately differentiate viral from bacterial meningitis. White blood cell count (cells per microliter) is typically 1000 to 10,000 (range, < 100 to > 10,000) with bacterial and less than 300 (range < 100 to 1000) with viral meningitis. Neutrophils are typically more than 80% vs less than 20%; protein levels elevated vs normal; and glucose levels reduced vs normal, respectively. However, these general predictions do not always hold true. The authors therefore recommend prospective studies to evaluate the diagnostic accuracy of signs, symptoms, and cerebrospinal fluid results in patients with suspected bacterial meningitis.

Some studies suggest worsening patient outcome with increased delays between presentation and antibiotic administration. Early antibiotic treatment in the emergency department may improve survival compared with delayed antibiotic treatment until after hospital admission.

"Although some guidelines attempt to propose an arbitrary time-based goal for antibiotic administration, others feel that a specific time point has not yet been identified as essential, but instead focus on level of disease severity and antibiotic administration as soon as possible once the diagnosis is considered," the authors write. "Until prospective data are available to support this practice, we suggest rapid administration of antibiotic therapy in the emergency department.... It is important to remember that the recommendations for CT scan include the caveat that patients who undergo CT first should have blood cultures and antibiotics started before ordering the CT scan."

Practice guidelines and expert opinions recommend broad spectrum coverage pending bacterial identification. The choice of initial antibiotic must be based on the most common bacteria causing the disease, according to the patient's age, clinical setting, and local patterns of antimicrobial susceptibility.

Empirical coverage with a third-generation cephalosporin (cefotaxime or ceftriaxone) at appropriate doses for meningitis is recommended, based on a broad spectrum of activity and excellent penetration into the cerebrospinal fluid when the meninges are inflamed. Because of the increasing prevalence of multidrug-resistant Streptococcus pneumoniae in many parts of the world (as high as 35% in parts of the United States), most experts recommend adding vancomycin to initial empirical therapy in adult patients. Patients older than 50 years should have ampicillin added for additional coverage of Listeria monocytogenes, which is more common in this age group.

This review recommends giving adult patients with suspected bacterial meningitis dexamethasone, 10 mg intravenously, with the first dose of antibiotics in the emergency department.

“The intense inflammatory response to bacterial infection within the enclosed spaces of the brain and spinal cord is thought to lead to significant morbidity and mortality despite effective antibiotic therapy,” the authors conclude. “Therefore, pharmacological attempts to modulate this inflammatory response may be an essential component of a successful strategy to treat this life-threatening disease, and dexamethasone is the only currently accepted adjunctive therapy for the treatment of patients with bacterial meningitis that has proven clinical efficacy.”

The Brooks Scholars in Academic Medicine award at the Wake Forest University School of Medicine; the Meningitis Research Foundation in the United Kingdom; Meerwaldt Foundation in the Netherlands; the Netherlands Organization for Health Research and Development (ZonMw) in the Netherlands; NWO-Rubicon; and NWO-Veni supported this study. The authors have disclosed no relevant financial relationships.

Lancet Infect Dis. 2007;7:191-200.

Clinical Context

The estimated annual incidence of bacterial meningitis in developed countries is 0.6 to 4 cases per 100,000 adults. The routine use of vaccines against Haemophilus influenzae and S pneumoniae has decreased the incidence of meningitis secondary to these organisms, although S pneumoniae remains one of the most common bacteria responsible for meningitis, along with N meningitis.

The prompt evaluation and treatment of patients with suspected bacterial meningitis is paramount to successful care of these patients. The current review cites the best practices for the acute treatment of adults with suspected meningitis.

Study Highlights

• The classic triad of symptoms of bacterial meningitis includes fever, stiff neck, and alterations of mental status. However, only two thirds of adults may present with all of these symptoms. Fever appears to be the most common symptom of this triad among adults with meningitis, and the presence of any of these symptoms is highly sensitive for detecting bacterial meningitis. The absence of any of the triad of symptoms should prompt an evaluation for other etiologies of patient symptoms.
• Specific physical signs, such as Kernig’s sign, Brudzinski’s sign, and nuchal rigidity, carry a low sensitivity for detecting bacterial meningitis, but Kernig’s and Brudzinski’s signs are fairly specific. Rash is present in only a minority of cases of bacterial meningitis.
• Clinicians may be concerned regarding the possibility of cerebral herniation following lumbar puncture among patients with suspected meningitis, and this may prompt the use of CT imaging prior to lumbar puncture and delay medical treatment. The current review suggests that the relationship between lumbar puncture and brain herniation is tenuous, but CT should be considered prior to lumbar puncture among a subset of patients with a possible cerebral space-occupying lesion or brain shift along with suspected meningitis. Such patients include those with new-onset seizures, moderate-to-severe impairment of consciousness, a history of immunocompromise, and evidence of space-occupying lesions such as papilloedema and focal neurologic signs.
• Classic cerebrospinal fluid findings among patients with bacterial meningitis include white blood cell count more than 1000 cells per microliter, more than 80% neutrophils on white blood cell differential, elevated protein levels, and reduced glucose levels. However, approximately 10% to 20% of adults with bacterial meningitis do not have typical laboratory findings.
• Prompt initiation of treatment of patients with suspected bacterial meningitis is essential. One study found worse outcomes among patients who received antibiotics at more than 3 hours after presentation. For adults younger than 50 years, empiric treatment should consist of 2 g of ceftriaxone or 2 g of cefotaxime plus 1 g of vancomycin plus 10 mg of dexamethasone intravenously. Ampicillin 2 g intravenously should be added for patients at age 50 years or older for possible infection with L monocytogenes.
• The authors recommend treatment with dexamethasone every 6 hours for 4 days for adults with bacterial meningitis. Dexamethasone should be initiated before or during the initial dose of antibiotics.

Pearls for Practice

• Classic cerebrospinal fluid findings among patients with bacterial meningitis include white blood cell count of more than 1000 cells per microliter, more than 80% neutrophils on white blood cell differential, elevated protein levels, and reduced glucose levels.
• For adults younger than 50 years, empiric treatment of suspected bacterial meningitis should consist of 2 g of ceftriaxone or 2 g of cefotaxime plus 1 g of vancomycin plus 10 mg of dexamethasone intravenously. Ampicillin 2 g intravenously should be added for patients at age 50 years or older for possible infection with L monocytogenes.

Reuters

A fruity cocktail may not only be fun to drink but may count as health food, U.S. and Thai researchers said on Thursday.

Adding ethanol — the type of alcohol found in rum, vodka, tequila and other spirits — boosted the antioxidant nutrients in strawberries and blackberries, the researchers found.

Any colored fruit might be made even more healthful with the addition of a splash of alcohol, they report in the Journal of the Science of Food and Agriculture.

Dr. Korakot Chanjirakul and colleagues at Kasetsart University in Thailand and scientists at the U.S. Department of Agriculture stumbled upon their finding unexpectedly.

They were exploring ways to help keep strawberries fresh during storage. Treating the berries with alcohol increased in antioxidant capacity and free radical scavenging activity, they found.

Any colored fruit or vegetable is rich in antioxidants, which are chemicals that can cancel out the cell-damaging effects of compounds called free radicals.

Berries, for instance, contain compounds known as polyphenols and anthocyanins. People who eat more of these fruits and vegetables have a documented lower risk of cancer, heart disease and some neurological diseases.

The study did not address whether adding a little cocktail umbrella enhanced the effects.

The Food and Drug Administration (FDA) approved Altabax (retapamulin ointment) for topical treatment of impetigo (http://www.nlm.nih.gov/medlineplus/impetigo.html), a skin infection caused by bacteria. Altabax is indicated for use in patients aged nine months or older. Retapamulin is a new molecular entity (NME) not previously approved in the United States.

Altabax was approved on the basis of effectiveness data from a placebo-controlled study supported by a study comparing Altabax to another antibiotic. The safety database contained approximately 2,000 Altabax-treated adults and children aged nine months and older, and about 1,000 similar patients who received different antibiotics or placebo. The most common Altabax-related adverse event was irritation at the site of the application, which occurred in less than two percent of the patients.

To reduce the development of drug-resistant bacteria, and maintain the effectiveness of Altabax and other antibacterial drugs, this product should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. This product will be available by prescription.
 
Altabax is manufactured by GlaxoSmithKline, Research Triangle Park, NC 27709.

####

Intro:  MRSA comminty-acquired pneumonia is rare but deadly, even in kids.  Suspect it in patients who have had or were in contact who has had a recent MRSA skin infection.  Then treat with vancomycin or linezolid. 

MMWR Press Summary, 4/12/07: 

Severe Methicillin-Resistant Staphylococcus

CDC Press Release, 4/12/07:  The Centers for Disease Control and Prevention (CDC) no longer recommends antibiotics known as fluoroquinolones (ciprofloxacin, ofloxacin, and levofloxacin) as a treatment for gonorrhea in the United States. This limits the options available to treat gonorrhea, one of the most common sexually transmitted diseases in the United States.

The recommendation was prompted by new data released today in CDC’s Morbidity and Mortality Weekly Report (MMWR) showing that fluoroquinolone-resistant gonorrhea is now widespread in the United States among heterosexuals and men who have sex with men (MSM). The data showed the proportion of drug-resistant cases among heterosexuals rising above the recognized threshold of 5 percent for changing treatment recommendations. CDC had recommended fluoroquinolones no longer be used to treat gonorrhea in MSM when this threshold was crossed in earlier years.

The new data, from CDC’s Gonococcal Isolate Surveillance Project (GISP) in 26 U.S. cities, showed that among heterosexual men, the proportion of gonorrhea cases that were fluoroquinolone-resistant Neisseria gonorrhoeae (QRNG) reached 6.7 percent in the first half of 2006, an 11-fold increase from 0.6 percent in 2001.

Recommended options for treating gonorrhea are now limited to a single class of antibiotics known as cephalosporins. Public health officials believe the lack of treatment options underscores the need for accelerated research into new drugs, as well as increased efforts to monitor for emerging drug resistance, especially to cephalosporins.

“There is also an urgent need for new, effective medicines to treat gonorrhea. We are running out of options to treat this serious disease,” said Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. “Increased vigilance in monitoring for resistance to all available drugs is essential.”

While significant resistance to cephalosporins has not been observed to date, CDC is working with state and local health departments to monitor emerging cephalosporin resistance. CDC is urging health departments to maintain or develop capacity to perform cultures for Neisseria gonorrhoeae and to assess any gonorrhea treatment failures for possible resistance. In addition, CDC is working with the World Health Organization to strengthen international efforts to monitor for the emergence of cephalosporin resistance and with government and industry partners to identify and evaluate promising new drug regimens. These additional measures are critical for the control of gonorrhea.

Oral fluoroquinolones were recommended as first-line treatments for gonorrhea in 1993. But drug resistant cases have increased steadily in recent years, rising first in the western United States and then among MSM nationwide. In 2002, CDC recommended that fluoroquinolones not be used to treat gonorrhea infections acquired in California and Hawaii, and in 2004 that the drugs no longer be used to treat MSM with these infections.

The new CDC analysis shows an increase in the past five years in the overall proportion of gonorrhea cases that are fluoroquinolone-resistant – from less than 1 percent in 2001 to 13.3 percent in the first half of 2006. The analysis also indicated that fluoroquinolone resistance is widespread geographically. Resistant cases were seen across the United States in the first half of 2006 (in 25 of the 26 cities in the analysis), and sharp increases occurred from 2004 to 2006 in several cities, including Philadelphia (from 1.2 percent to 26.6 percent of gonorrhea cases) and Miami (from 2.1 percent to 15.3 percent). In addition, the analysis showed QRNG continued to rise among MSM; 38 percent of MSM gonorrhea cases were QRNG in the first half of 2006, compared to 1.6 percent in 2001.

Within the class of cephalosporins, CDC now recommends ceftriaxone, available as an injection, the preferred treatment for all types of gonorrhea infection (genital, anal, and throat). For genital and anal gonorrhea, there are some alternative oral cephalosporin treatments that physicians can consider, but there are currently no recommended alternatives for pharyngeal infection.

Additional information on available gonorrhea treatments can be found at: www.cdc.gov/std/gonorrhea/arg/.

“New treatment recommendations are critical if we are to continue to see progress in controlling gonorrhea,” said Dr. John Douglas, director of the Division of STD Prevention. “We cannot afford to lose ground against a disease that continues to affect roughly 700,000 Americans each year.”

Gonorrhea is the second most commonly reported infectious disease in the United States after chlamydia. In 2005, 339,593 cases were reported nationwide, although experts believe the actual number of cases may be twice that. Following a substantial decline in national gonorrhea rates from 1975 to 1997, overall rates appear to have leveled off in recent years.

In a page-one story, the New York Times (4/13, A1, Altman) reports that “the rates of drug-resistant Gonorrhea in the U.S. have increased so greatly in the last five years that doctors should now treat the infection with a different class of antibiotics,” according to officials from the Centers for Disease Control and Prevention. “The percentage of drug-resistant Gonorrhea cases among heterosexual men jumped, to 6.7 percent in 2006 compared with 0.6 percent in 2001,” CDC said. “Standard monitoring of Gonorrhea cases is conducted among men who go to STD clinics. New data from such sites in 26 cities show that rates of drug-resistant Gonorrhea among heterosexual men at the clinics last year reached 26 percent in Philadelphia and more than 20 percent in Honolulu and four areas in California, Long Beach, Orange County, San Diego and San Francisco.” UPI (4/13) adds, “Among men who have sex with men, 38 percent of Gonorrhea cases were resistant to fluoroquinolones.”
      The Wall Street Journal /AP (4/13) reports that “fluoroquinolones, a class of antibiotics that includes Cipro (ciprofloxacin), have been the most common way to treat the bacterial disease since the early 1990s. Since then, Gonorrhea has grown increasingly resistant to those drugs. On Thursday, the CDC recommended that a different class of antibiotics, cephalosporins, be used instead.” The CDC made the “new recommendation after discovering that nearly 7 percent of Gonorrhea cases among heterosexual men in a survey of 26 U.S. cities last year had drug-resistant strains of the disease.”
      The Washington Post (4/13, A3, Stein) reports, “The emergence of resistant Gonorrhea marks the latest common pathogen to have shifted from an easily treated infection to a resistant form that is suddenly far more dangerous. … Gonorrhea’s resistance was probably caused by the same problem that led to resistance of other organisms — the casual use of antibiotics in the U.S. and overseas, which causes pathogens to mutate,” Dr. John M. Douglas, Jr., who heads the CDC’s division of sexually transmitted disease prevention, and others said.
      USA Today (4/13, Rubin) adds that Douglas said, “‘Third-generation’ cephalosporins have been used for nearly 25 years, but there have been no signs that Gonorrhea is becoming resistant to them. Still, he said, it could happen, which is why the CDC asks state and local public-health authorities to step up their monitoring for cephalosporin-resistant Gonorrhea. The agency is also working more closely with the World Health Organization to monitor cephalosporin resistance in Gonorrhea worldwide.” However, “the main drawback with cephalosporins is that the preferred drug in the class is given in an injection, while fluoroquinolones come in pill form, Douglas said.”
      Newsday (4/13, Ricks) adds that Dr. Douglas “said 700,000 cases of the infection are reported annually in the U.S. But he underscored that cases are underreported and underdiagnosed. In women, he said, the infection develops so silently that many do not even know they are infected.”
      Bloomberg (4/13, Larkin) adds that the “new recommendations tell doctors to treat all types of Gonorrhea infections with injections of ceftriaxone, sold by Basel, Switzerland-based Roche as Rocephin and by several makers of generic drugs. Certain types of Gonorrhea may also be treated with other cephalosporins, the CDC said.”
      HealthDay (4/13, Preidt) reports the CDC data is published in today’s edition of CDC’s Morbidity and Mortality Weekly Report. “Along with switching to cephalosporins to treat Gonorrhea, the CDC recommends increased monitoring for cephalosporin-resistant Gonorrhea and accelerated research into new treatments for the disease.” Also, according to the NIH, “Gonorrhea is the second most commonly reported bacterial sexually transmitted infection in the U.S., following Chlamydia. In 2004, there were 330,132 Gonorrhea cases reported to the CDC. The highest rates of Gonorrhea are found in African-Americans, 15 to 24 years of age, and women.” The CDC also issued a press release summarizing its findings.
      WebMD (4/13, Hitti) adds that Douglas said, “There are currently no new drugs for Gonorrhea in the drug-development pipeline.”

The New York Times (3/31, Harris) reported that Novartis, “the maker of Zelnorm (tegaserod), a medicine that treats constipation-related irritable bowel syndrome (IBS), stopped selling the drug Friday” after FDA officials concluded that “it might cause heart attacks and strokes. In 29 studies, 13 of 11,614 patients given Zelnorm had heart problems, including one who died. Just one of 7,031 patients given placebos had similar problems. Officials at the FDA said the drug was not effective enough to merit such risks.”
      In a statement (3/30), the FDA said it is “currently advising patients who are using Zelnorm to contact their health-care providers to discuss treatment alternatives. Patients who are taking Zelnorm should seek emergency medical care if they experience severe chest pain, shortness of breath, dizziness, sudden onset of weakness or difficulty walking or talking, or other symptoms of a heart attack or stroke.”
      The Washington Post /AP (3/31, A3) quoted Stephen Cunningham, VP and head of U.S. clinical development and medical affairs at Novartis, who said, “Although we have complied with the FDA’s request and are collaborating with the agency, we continue to believe that Zelnorm provides important benefits for appropriate patients.”
      The Wall Street Journal (3/31, A5, Mathews, Whalen) added that when an earlier drug “for a different type of IBS, Lotronex (alosetron), was pulled from the market, patients successfully lobbied for its return.”
      Medpage Today (3/31, Peck) reported that “tegaserod is the only FDA-approved treatment for IBS with predominant constipation, and the FDA said that it recognized that the withdrawal posed clinical management problems for patients who use the drug for that indication.” To ease those difficulties, the FDA said it was “working with Novartis to set up a program that will allow access to the drug under an investigational new drug application.” However, “a statement from Novartis said that the company was not convinced of a causal link between tegaserod and ischemic events. The statement noted — and FDA officials agreed — that the 13 cases identified in the pooled analysis occurred in people with a history of cardiovascular disease, including prior myocardial infarction.” Novartis “also released a statement from Jeffrey L. Anderson, M.D., a professor of internal medicine at the University of Utah and the associate chief of cardiology, who was identified as an independent cardiologist who reviewed the pooled data. Dr. Anderson concluded that a causal relationship was unlikely.”
      The Chicago Tribune (4/1) noted that physicians said the “voluntary withdrawal of Zelnorm by its manufacturer will leave few options for the roughly 12-million Americans, mostly women, who suffer from a type of IBS. ‘This is really a sort of one-of-a-kind drug,’ said Dr. Bennett Roth, chief of gastroenterology at the University of California, Los Angeles, Medical Center. ‘It doesn’t work for everybody, but in those for whom it works, it gets pretty good results.’”
      WebMD (3/31, Zwillich) also reported on Zelnorm’s removal from the U.S. market.