Practice Guidelines
Management of Bacterial Meningitis: New Guidelines from the IDSA
The Infectious Diseases Society of America (IDSA) has issued new guidelines for the diagnosis and treatment of bacterial meningitis. Recommendations are based on results from clinical trials and data from animal experimentation published through May 2004. The guidelines were published in the November 1 issue of Clinical Infectious Diseases, and can be accessed online at http://www.journals.uchicago.edu/CID/journal/issues/v39n9/34796/34796.text.html. Definitions of strength of recommendations and quality of evidence are listed in Table 1.
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TABLE 1 IDSA-United States Public Health Service Grading System for Ranking Recommendations in Clinical Guidelines |
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Initial Management Steps
When a patient presents with suspected acute bacterial meningitis, the physician should begin antimicrobial therapy as soon as possible. Bacterial meningitis is a neurologic emergency; progression to more severe disease reduces the patient's likelihood of a full recovery.
A blood culture and lumbar puncture should be performed immediately to confirm the diagnosis. Because complications associated with lumbar puncture include life-threatening brain herniation, at-risk patients (e.g., those who are immunocompromised, had a seizure within the previous week [adults only], have papilledema, or have a specific neurologic abnormality) should have a computed tomographic (CT) scan before undergoing the procedure (B-II). Lumbar puncture also may be delayed pending CT scan results if it may be likely that symptoms are caused by increased intracranial pressure from, for example, a central nervous system mass lesion. Blood samples still should be obtained from patients immediately, and appropriate empiric therapy administered. Once a negative CT scan result is obtained, patients can proceed to lumbar puncture.
Empiric therapy. Empiric therapy should begin as soon as bacterial meningitis is thought likely. Widespread resistance to penicillins and sulfonamides has forced a consideration of new agents for the treatment of bacterial meningitis, such as cephalosporins, vancomycin (Vancocin), rifampin (Rifadin), carbapenems, and fluoroquinolones. Choice of agents for empiric therapy should be determined by the patient's age and the presence of predisposing conditions, and should assume antimicrobial resistance. Recommendations are listed in Table 2 (A-III).
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TABLE 2 Recommendations for Empiric Antimicrobial Therapy for Purulent Meningitis Based on Patient Age and Specific Predisposing Condition |
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Adjunctive Dexamethasone Therapy. The addition of dexamethasone also should be considered. Adjunctive dexamethasone can reduce the subarachnoid space inflammatory response-a major factor in morbidity and mortality caused by bacterial meningitis-and may therefore alleviate many of the pathologic consequences of bacterial meningitis (e.g., cerebral edema, cerebral vasculitis, change in cerebral blood flow, increase in intracranial pressure, neuronal injury). There is some concern that adjunctive dexamethasone therapy may inhibit the efficacy of cerebrospinal fluid (CSF) vancomycin and would therefore be harmful to patients with penicillin- or cephalosporin-resistant strains. However, in the absence of data from clinical trials, adjunctive dexamethasone is recommended for all adults with suspected or proven pneumococcal meningitis, and in infants and children with Haemophilus influenzae type b meningitis (A-I), even if the isolate subsequently is found to be highly resistant to penicillin or a cephalosporin. Patients should be observed closely in follow-up to check for any adverse outcomes. Recommended dosage of dexamethasone is 0.15 mg per kg administered every six hours for two to four days, beginning 10 to 20 minutes before (or at least concomitant with) the first antimicrobial dose (A-I). Patients receiving adjunctive dexamethasone for the treatment of suspected pneumococcal meningitis may benefit from the addition of rifampin to the combination of vancomycin and a third-generation cephalosporin.
The use of dexamethasone in infants and children with pneumococcal meningitis is controversial, and there are insufficient data to support its use in neonates or in adults with meningitis caused by other pathogens. Patients who already have received antimicrobial therapy should not be given dexamethasone therapy, as it is unlikely to improve their outcome (A-I). Dexamethasone therapy should be continued following test results only if gram-positive diplococci are found in the CSF Gram stain, or if cultures reveal Streptococcus pneumoniae.
Diagnosis
Diagnosis of bacterial meningitis is dependent on CSF examination following lumbar puncture. In bacterial meningitis, opening pressure generally is between 200 and 500 mm H2O (lower in children); white blood cell count and protein concentration are elevated; glucose concentration may be low; and there may be a neutrophil or lymphocyte predominance.
Because determining the bacterial etiology can take up to 48 hours with CSF cultures, an alternative diagnostic test should be considered.
Gram stain examination of CSF is recommended for all patients in whom meningitis is suspected (A-III). It is fast, inexpensive, and accurate in 60 to 90 percent of patients, although misinterpretation and contamination may cause false-positive results.
Polymerase Chain Reaction (PCR) is useful for excluding a diagnosis of bacterial meningitis and may eventually, with further refinement, be used for determining etiology (B-II).
Latex agglutination, while quick, simple, and sensitive, is not recommended for routine use as pathogens cannot be ruled out by a negative test result (D-II). It is most useful for patients who have begun therapy and have negative Gram stain and CSF culture results.
Limulus lysate assay, though sensitive, also is not recommended for routine use (D-II) as it does not distinguish between organisms or rule out gram-negative meningitis, and it is not widely available.
When CSF findings suggest bacterial meningitis but CSF Gram stain and culture results are negative, a combination of laboratory tests is necessary to distinguish bacterial from viral meningitis. (Although there is a validated CSF result model, its clinical utility has not yet been proven, and it should not be used to determine initiation of antimicrobial therapy.) The most strongly recommended tests are PCR, which is more sensitive than viral culture and faster than cell culture for the detection of enterovirus, and determination of C-reactive protein (CRP) concentration, which has a high negative predictive value for bacterial meningitis when results are normal (B-II).
Lactate concentration is not recommended (D-III) since results generally are nonspecific and may be confounded by other factors (although a CSF lactate concentration of 4.0 mmol per L or greater may be used as an indication for empirical therapy in postoperative neurosurgical patients [B-II]).
Procalcitonin concentration measurement is useful, but cannot be recommended until it becomes more widely available (C-II).
Management
Targeted antimicrobial therapy can begin in adults following a positive CSF Gram stain result. (Note that empiric antibiotic therapy should not be delayed pending the results of Gram stain or other diagnostic tests.) Children should not be given targeted therapy until blood culture results confirm the diagnosis, since CSF Gram stain interpretation is subject to expertise. In the meantime, they should receive empiric therapy with vancomycin plus either ceftriaxone (Rocephin) or cefotaxime (Claforan). Patients whose Gram stain result is negative also should continue with empiric therapy.
Antimicrobial therapy should be
modified as soon as the pathogen has been isolated and in vitro tests have been
performed. Duration of therapy depends on individual patient response, though
generalized guidelines according to the responsible pathogen are as follows:
Neisseria meningitidis
or H. influenzae, seven days;
S. pneumoniae, 10 to 14 days;
Streptococcus agalactiae,
14 to 21
days; aerobic gram-negative bacilli, 21 days (two weeks beyond the first
sterile CSF culture in neonates); Listeria
monocytogenes, 21 days or longer. Intravenous therapy is recommended
throughout to maintain sufficient CSF concentrations.
In neonates with meningitis caused by gram-negative bacilli, the duration of therapy should be determined in part by repeated lumbar punctures documenting CSF sterilization (A-III). Patients who have not responded clinically after 48 hours of appropriate therapy also should be monitored with repeated CSF analysis (A-III), particularly those with meningitis caused by resistant strains and those who have received adjunctive dexamethasone therapy. Repeated CSF analysis is not recommended on a routine basis.
Because any complications of
bacterial meningitis usually occur within the first two or three days of
treatment, carefully selected patients may be eligible for outpatient
management, with close follow-up. Criteria for outpatient therapy are inpatient
antimicrobial therapy for six or more days; no fever for at least
24 to 48
hours; no significant neurologic dysfunction, focal findings, or seizure
activity; stable or improving condition; ability to take fluids by mouth; safe
environment with access to a telephone, a refrigerator, food, utilities, and
home health nursing; reliable intravenous line and infusion device, if
necessary; physician available daily; and an established plan for physician and
nurse visits, laboratory monitoring, and emergencies.
Antimicrobial Agents
Cephalosporins. Third-generation cephalosporins (cefotaxime or ceftriaxone) are recommended for the treatment of childhood bacterial meningitis (A-I) and for pneumococcal and meningococcal meningitis caused by penicillin-resistant strains (A-III). They are the drugs of choice for empiric therapy in the treatment of H. influenzae type b meningitis, because resistance to chloramphenicol has developed. Third-generation cephalosporins have shown greater efficacy than chloramphenicol (Chloromycetin) and the second-generation cephalosporin cefuroxime (Ceftin). They are effective in meningitis caused by aerobic gram-negative bacilli (A-II), but increasing resistance makes in vitro susceptibility testing crucial. Ceftazidime (Ceptaz) has proved effective in the treatment of Pseudomonas meningitis (A-II). Cefepime (Maxipime), a fourth-generation cephalosporin, has proved safe and effective in the treatment of infants and children with bacterial meningitis, and has been used successfully in patients with bacterial meningitis caused by Enterobacter species and Pseudomonas aeruginosa (A-II).
Vancomycin. The use of vancomycin is not recommended in patients with bacterial meningitis caused by non-resistant strains (E-II). In patients with meningitis caused by penicillin- or cephalosporin-resistant strains it may be used in combination with a third-generation cephalosporin but should not be used alone (A-III). If a patient is unresponsive to parenteral administration, intrathecal administration may be considered.
Rifampin. Rifampin should be used only in combination with other antimicrobial agents as resistance develops rapidly when it is used alone. It has been used in combination with a third-generation cephalosporin with or without vancomycin for treatment of pneumococcal meningitis caused by penicillin- or cephalosporin-resistant strains, though data on its efficacy are lacking. The addition of rifampin is recommended only if clinical or bacteriologic response to a susceptible pathogen is delayed (A-III).
Carbapenems. Imipenem (Primaxin) has proved successful, but is not recommended for treatment of meningitis in most patients because of the potential for seizure activity (D-II). Meropenem (Merrem) has less potential for seizure and is recommended as an alternative to cefotaxime and ceftriaxone in the treatment of patients with bacterial meningitis (A-I), and for use in the treatment of meningitis caused by certain gram-negative bacilli (A-III). Although meropenem is effective in treating patients with pneumococcal meningitis caused by penicillin- or cephalosporin-resistant strains, the prevalence of strains with shared resistance may undermine its usefulness (D-II).
Fluoroquinolones. The use of fluoroquinolones in the treatment of bacterial meningitis is recommended when patients are unresponsive to or cannot be given standard antimicrobial therapy, or when meningitis is caused by gram-negative bacilli that are resistant to multiple agents (A-III). Newer fluoroquinolones, such as gatifloxacin (Tequin) and moxifloxacin (Avelox), potentially are useful in treating bacterial meningitis, but should be used only as alternative agents until more evidence is produced (B-II). There are no data on the use of these agents in newborns and children, although they may be considered in these patients when standard therapy is ineffective. Trovafloxacin (Trovan) no longer is used owing to possible liver toxicity.
Practice Guideline Briefs
Improving the Quality of Care for Patients with Hypertension
The Agency for Healthcare Research and Quality (AHRQ) of the U.S. Department of Health and Human Services has published a technical review on improving the quality of care for patients with hypertension. "Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies. Volume 3 - Hypertension Care” (AHRQ Publication no. 04-0051-3) was released in January 2005 and is available online at http://www.ahrq.gov/clinic/evrptpdfs.htm#qualgap2.
The authors searched MEDLINE, the Cochrane Effective Practice and Organisation of Care Review Group registry, and other databases, and hand searched bibliographies and articles for experimental evaluation of quality-improvement interventions in the care of nonpregnant patients with primary hypertension.
Quality improvement targets included measures of blood pressure screening (i.e., strategies to increase the awareness of hypertension in undiagnosed patients) and control (i.e., the percentage of diagnosed patients whose blood pressure is within the range recommended by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure [less than 120/80 mm Hg]). Sixty-three articles met the inclusion criteria. The strategies assessed in the studies were organizational change, education of patients and health care professionals, facilitated relay of clinical data, audit and feedback, promotion of self-management, reminders for physicians and patients, and financial incentives.
The authors' findings suggest that quality improvement strategies are associated with improved detection and control of hypertension, but they could not discern which strategies have the greatest effect. Studies that involved organizational change appeared to have the largest positive effect; however, there were some methodologic concerns about confounding because of study size, and the authors note that organizational change may be only an indication of high levels of administrative support or funding. Patient education also appeared to have a large positive effect, but the results were confounded by study size. Studies that focused on improving physician adherence to recommendations for hypertension management had less effect. The authors noted that there may be several reasons for this, including rapidly changing recommendations and time and resource constraints.
The authors concluded that the most noticeable finding was the need for more high-quality research to clarify the best strategies with which to improve the care of patients with hypertension.
Use of Antiretrovirals to Prevent HIV Infection from a Nonoccupational Source
The Centers for Disease Control and Prevention has published a recommendation report on the use of antiretroviral drugs to prevent human immunodeficiency virus (HIV) infection after injection-drug use, sexual, and accidental exposure. "Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States” was released January 21, 2005, and is available online at http://www.cdc.gov/mmwr/mmwr_rr.html. The report summarizes information about the use of nonoccupational postexposure prophylaxis and lists guidelines for its use.
Recent data from human and animal studies, case reports, and documentation of the use of nonoccupational postexposure prophylaxis prompted the U.S. Department of Health and Human Services to update its recommendation for the use of nonoccupational postexposure prophylaxis in patients who seek treatment within 72 hours of high-risk exposure to a person known to be HIV positive.
According to the authors, when highly active antiretroviral therapy (HAART) is prescribed within 48 to 72 hours of nonoccupational exposure to HIV and continued for 28 days, the likelihood of transmission may be reduced. The earlier the nonoccupational postexposure prophylaxis is administered, the higher the chance that it will interrupt transmission.
The authors state that no specific antiretroviral medication or combination is optimal for nonoccupational postexposure prophylaxis. However, preferred regimens include efavirenz and lamivudine or emtricitabine with zidovudine or tenofovir (as a nonnucleoside-based regimen) and lopinavir and ritonavir (co-formulated in one tablet) and zidovudine with either lamivudine or emtricitabine. No evidence suggests that a three-drug HAART regimen is more effective than a two-drug regimen. When the source person is available for interview, his or her medication history and most recent viral load measurement should be considered when choosing medications for nonoccupational postexposure prophylaxis. This could help prevent prescription of medications to which the virus is already resistant.
According to the report, all patients seeking treatment after HIV exposure should be tested for antibodies at baseline, four to six weeks, three months, and six months. Patients should be informed about the signs and symptoms of acute retroviral infection and should be asked to return for evaluation if these occur. Physicians who provide nonoccupational postexposure prophylaxis also should monitor patients' liver function, renal function, and hematologic parameters.
When a patient's risk of transmission from contact is small or when more than 72 hours have passed since exposure, nonoccupational postexposure prophylaxis is not recommended. However, when a patient seeks treatment more than 72 hours after exposure, but the risk of virus transmission is severe, physicians may decide that the potential benefit of nonoccupational postexposure prophylaxis is greater than the potential risk of complications from antiretroviral therapy.
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| Copyright © 2005 by the American
Academy of Family Physicians. |
