ACUTE INFECTIONS OF THE CENTRAL NERVOUS SYSTEM
Acute Bacterial Meningitis
Aseptic Meningitis: Mixed Cellular Response
Viral and Granulomatous Meningitis: Lymphocytic Response
Ruptured Brain Abscess
Infections of the central nervous system (CNS) are associated with mortality and neurologic sequelae. Many are treatable by medical or combined medical and surgical measures. Invasive techniques may also play a diagnostic role. Acute CNS infections can be categorized as meningitis, encephalitis, or mass lesions (Table 33-1). They may differ significantly in clinical presentation, bacteriology, and clinical and laboratory assessment.
Table 33-1. Acute central nervous system infections
Table 33-2 presents recommendations for the initial evaluation of patients with acute CNS infections. Most patients present with a history of headache and fever. Nausea and vomiting are frequent complaints. The history provides data about the acuteness of presentation, acquisition status (e.g., community or nosocomial), and associated complaints. An epidemiologic history must be obtained, with attention to travel, animal and insect exposures, HIV risks, and recent immunizations. Intrathecal contrast dyes, ibuprofen, and antimicrobials such as trimethoprim-sulfamethoxazole (TMP-SMX) and isoniazid can cause acute meningeal reactions in the absence of infection. Knowledge of underlying illness provides important information about potential pathogens. Alcoholism (Streptococcus pneumoniae, Listeria monocytogenes), T cell-mediated immunosuppression such as AIDS (Toxoplasma gondii, Cryptococcus neoformans), cerebrospinal fluid (CSF) leaks (S. pneumoniae), and trauma (enteric gram- negative bacilli) are examples.
Table 33-2. Evaluation of acute central nervous system infections
Patients with HIV/AIDS present a special challenge, as the diseases that may manifest as acute CNS infections are diverse and significantly different from those seen in an immunocompetent population. In some instances, an acute CNS presentation is the initial manifestation of AIDS. Table 33-3 presents the most notable acute CNS diagnoses in patients with AIDS. These have important implications for diagnosis and management. Physical examination provides evidence of focal neurologic abnormalities and non-CNS foci of infection that can act as primary sites for spread. Ear, nose, and throat and cardiopulmonary abnormalities should be sought carefully. Rashes may be manifestations of bacteremia or Rocky Mountain spotted fever.
Table 33-3. Acute central nervous system infections in patients with AIDS
Routine laboratory data include a CBC, determination of electrolytes, and assessment of renal and hepatic function. Such information may provide evidence for a specific cause of the CNS disease (e.g., Reye’s syndrome, leptospirosis, hyponatremia) and baseline values against which to gauge changes resulting from disease or therapy. Blood cultures should be obtained in all patients. Suspected foci should be cultured and roentgenography performed as clinically indicated.
Lumbar puncture (LP) should be performed in most patients unless contraindicated by evidence of substantial elevations of intracerebral pressure. Fluid from an LP should be submitted for Gram’s stain and culture (tube 1), glucose and protein analysis (tube 2), and cell count and differential (tube 3). Usually, at least one additional tube should be retained should other tests be needed. These might include Venereal Disease Research Laboratory (VDRL) tests and counterimmunoelectrophoresis (CIE) or latex particle agglutination tests for bacterial antigens, cryptococcal antigen testing, Lyme serology, smears, cultures for mycobacteria and fungi, viral cultures or polymerase chain reaction (PCR) studies, and cytocentrifugation for malignancy. Patients with AIDS may present with a multiplicity of unusual organisms that include C. neoformans, HIV, T. gondii, and other opportunists. In geographic areas with significant populations of patients with HIV/AIDS, routine CSF testing for cryptococcal antigen and VDRL tests should be performed.
Typical symptoms of meningitis are fever, headache, nausea and vomiting, and nuchal rigidity. Many patients may not experience all these, especially early in the course of disease. Nuchal rigidity is most often associated with acute bacterial meningitis or tuberculous meningitis. Acute or subacute meningitis present for less than 7 days has numerous potential causes, and the prognosis may be improved by prompt diagnosis, particularly if the disease is bacterial. Focal neurologic defects may be noted with “uncomplicated” disease in up to 28% of patients; however, assessment for a mass lesion should be undertaken. The LP may provide specific diagnostic information.
Patients with bacterial meningitis who are not immunosuppressed generally demonstrate CSF leukocytosis. Classic categories for elevations of CSF leukocyte counts are as follows: polymorphonuclear, mixed cellular, and lymphocytic response. Although attempts to classify causes by type of cellular response may be useful, much overlap exists. Additionally, in the granulocytopenic patient, bacterial meningitis may develop with symptoms of fever and obtundation but without significant abnormalities of CSF WBC count. Similarly, in the patient with AIDS and cryptococcal meningitis or other opportunistic infections, the WBC response may be small or absent despite the presence of active infection.
Acute Bacterial Meningitis
Recent data suggest that acute bacterial meningitis has an annual incidence of about 4/100,000. In cases of community-acquired disease, Neisseria meningitidis, S. pneumoniae, and L. monocytogenes are most prevalent. Variations among age groups exist, with N. meningitidis more common among younger persons and S. pneumoniae and L. monocytogenes most common among the elderly. Seizures occur in about 10% of cases and are more frequent with pneumococcal meningitis. Mortality rates for bacterial meningitis in adults remain at approximately 20% but rise to at least 40% among those over age 60.
For patients without prior antibiotic therapy, CSF leukocytosis with counts above 1,000/mm3 is usual, results of Gram’s stains are positive in 50% to 75% of cases, and results of cultures are positive at least about 90% of the time. Prior antibiotics decrease rates of positivity of both Gram’s stain and culture. When cell counts are below 500/mm3, many patients with bacterial meningitis may demonstrate lymphocytic responses, at least early in the course. Hypoglycorrhachia and elevated protein are anticipated; however, a recent study demonstrated that only 50% of patients had the former. In at least 20% of cases of meningitis caused by N. meningitidis, cell counts are below 100/mm3. Culture-positive pyogenic meningitis associated with normal LP results has been rarely reported.
When the Gram’s stain is negative, CSF antigen-detection tests should be performed. These have the capacity to detect bacterial antigen in the absence of viable organisms. S. pneumoniae, H. influenzae type B, most strains of N. meningitidis, and group B streptococci may be detected in this manner. False-negative reactions occur, and gram-negative enteric bacilli and L. monocytogenes cannot currently be identified in this fashion.
Recently, bacterial meningitis associated with the use of epidural catheters for treatment of pain has been described. Risk for infection is associated with length of surgery for catheter placement and probably with duration of catheter placement. In these circumstances, meningitis may occur in association with other focal infections, including muscle abscess, and therapy includes removal of the catheter, drainage of collections, and administration of appropriate antibiotics. Organisms most commonly encountered are Staphylococcus aureus, coagulase-negative staphylococci, and other skin flora.
Gram-negative bacillary meningitis is associated with surgical or nonsurgical trauma and comprises about 5% of all cases of bacterial meningitis. In the absence of such risks, nosocomial fever and mental status changes should not indicate the need for LP. Organisms most commonly implicated are Escherichia coli and species of Klebsiella. Acute purulent meningitis may be the initial manifestation of acute infective endocarditis. S. aureus is often a cause, and septic emboli are usually implicated. Drugs, intrathecal contrast dyes, and exploration of the posterior fossa have also been reported to cause such a response.
Therapy for acute bacterial meningitis requires bactericidal antimicrobials that are effective against the likely pathogens and capable of crossing the inflamed blood– brain barrier. Antibiotics meeting these qualifications include most third-generation cephalosporins, ampicillin, aqueous penicillin G, and TMP-SMX. Chloramphenicol is bactericidal against most strains of H. influenzae, meningococci, and some strains of S. pneumoniae, but bacteriostatic against L. monocytogenes and most enteric gram-negative bacilli.
Changing trends in S. pneumoniae resistance have dramatically altered the antibiotic recommendations for empiric treatment of bacterial meningitis. For suspected pneumococcal meningitis, or in the absence of a positive Gram’s stain or antigen detection, a third-generation cephalosporin (2 g of cefotaxime every 8 hours, or 2 to 4 g of ceftriaxone every 24 hours) plus vancomycin (1 g given intravenously every 12 hours) is now recommended pending organism identification and susceptibility testing. Aqueous penicillin G (24 million units per day) will treat infections caused by penicillin-sensitive S. pneumoniae or N. meningitidis, and L. monocytogenes. The need to add an aminoglycoside for the latter agent has been poorly substantiated. Four grams of chloramphenicol per day given intravenously is an acceptable alternative in patients with pneumococcal or meningococcal meningitis who cannot tolerate b-lactam antimicrobials.
Third-generation cephalosporins in full parenteral doses for 2 to 3 weeks have revolutionized the therapy of gram-negative bacillary meningitis caused by susceptible pathogens. They are now widely considered to be the drugs of choice for this condition. However, Enterobacter organisms often acquire resistance to these agents after only several days, and the agent of choice in this case is probably TMP-SMX (20 mg of TMP equivalent per kilogram per day in two to four divided doses).
The use of ineffective agents or antimicrobials in suboptimal quantities results in higher mortality. Repeated LPs to document the efficacy of treatment are not necessary if the clinical condition is improving.
The length of therapy for bacterial meningitis is controversial. Meningococcal meningitis can usually be managed with 7 days of therapy. Disease caused by H. influenzae, L. monocytogenes, and S. pneumoniae should be treated for 10 to 14 days. Gram-negative bacillary meningitis usually requires up to 3 weeks of treatment. Outpatient IV antimicrobial therapy can be employed for clinically stable patients to complete the course of treatment.
The efficacy of corticosteroids in adults with meningitis remains unproven. This author would use them in patients with meningococcal disease and shock.
Aseptic Meningitis: Mixed Cellular Response
“Aseptic” meningitis usually presents with CSF pleocytosis and 40% to 60% polymorphonuclear leukocytes, and negative results on Gram’s stains and routine cultures. CSF glucose is typically normal. The course ranges from acute to chronic. Major differential diagnoses include (a) partially treated bacterial meningitis, (b) parameningeal foci (including emboli from infective endocarditis), (c) syphilitic, Lyme borreliosis, and leptospiral meningitis, and (d) early viral or granulomatous meningitis. Noninfectious conditions include heavy metal encephalopathy, seizures, and carcinomatous meningitis. The clinical approach depends on the status of the patient and pertinent historical and clinical information. If evidence of mass lesions is lacking and the illness is not fulminant, a repeated LP after 6 to 12 hours is indicated. At that time, a change toward either a lymphocytic or polymorphonuclear response may be seen, and CSF glucose may decline. A second LP is especially helpful for patients who may have partially treated bacterial meningitis or viral meningitis. However, some authorities recommend routine treatment of possible bacterial meningitis with subsequent discontinuation of drugs after 48 to 72 hours if assessment is negative.
Viral and Granulomatous Meningitis: Lymphocytic Response
A lymphocytic pleocytosis of fewer than 500 cells per cubic millimeter is most commonly seen in viral or granulomatous meningitis. However, some patients with bacterial meningitis may also present with this formula. Granulomatous meningitis (tuberculous, fungal, sarcoid) is often associated with hypoglycorrhachia, which is uncommon in viral meningitis. Tuberculous and fungal meningitis should be considered especially in patients with appropriate epidemiologic histories (including HIV risk factors), evidence of other foci of infection, and hypoglycorrhachia. Cryptococcal antigen tests and smears and cultures for acid-fast bacilli and fungi are indicated. Therapy for tuberculous meningitis may be necessary if other diagnoses cannot be rapidly proved. Intense lymphocytic pleocytosis with cell counts above 5,000/mm3 may be seen with lymphocytic choriomeningitis.
Cryptococcal meningitis is the most common type of meningitis in patients with AIDS and is not generally noted with CD4 counts above 100/mm3. Presentation is often headache, and initial LP results may demonstrate clear fluid and fewer than 10 cells. In areas endemic for AIDS, cryptococcal antigen testing should be performed routinely on CSF specimens.
Acute encephalitis represents inflammation of brain tissue and may occur concurrently with meningeal irritation (“meningoencephalitis”). Approximately 20,000 cases occur annually in the United States, representing 3.5 to 7.4 cases per 100,000 patient-years, and most are mild. Acute encephalitis is clinically characterized by fever, headache, and altered state of consciousness. Focal neurologic defects, seizures, and autonomic abnormalities may also occur. Herpes simplex encephalitis characteristically is associated with early behavioral disorders because the virus tends to localize in the temporal lobes. Seizures occur early in the course in about half of cases.
In the United States, most encephalitis in non-AIDS patients is viral. Isolated cases are most likely caused by herpes simplex virus or mumps virus but may also be seen with varicella-zoster virus, Epstein-Barr virus (often cerebellar), or rubeola virus. The incidence of herpes simplex is 1/250,000 to 500,000 persons per year, and about 2,000 cases occur annually. It is most common below age 20 or above age 50 and is associated with significant mortality (70%) and neurologic sequelae (almost 100%) if untreated. Thus, it must not be overlooked. When acute encephalitis is encountered with no obvious etiology, empiric therapy for herpes simplex is often warranted. Warm-weather outbreaks are often associated with enteroviruses (coxsackievirus, echovirus, and poliovirus) and togaviruses (equine encephalitis virus).
Nonviral and potentially treatable causes of encephalitis include Rocky Mountain spotted fever, malaria, brucellosis, amebic (Naegleria) infection, syphilis, Lyme borreliosis, and toxoplasmosis. The last is an important consideration when encephalitis presents in AIDS patients. Occasionally, chronic meningitides, such as those caused by Mycobacterium tuberculosis and C. neoformans, may be associated with encephalitis because of hydrocephalus. Measles and rabies vaccines can cause encephalitis. Reye’s syndrome, which often follows viral influenza and chickenpox, is a clinical condition that affects children primarily and can cause hepatic dysfunction.
Evaluation of encephalitis requires a comprehensive history, physical examination, and LP. Computed tomography (CT) with contrast or magnetic resonance imaging (MRI) with contrast is generally needed. Initial assessment should rule out treatable diseases, including herpes simplex. With the latter, LP usually reveals an “aseptic” or lymphocytic process with normal or depressed CSF glucose and elevated protein. RBCs in the CSF are often seen. Herpes simplex encephalitis should be suspected if behavioral disorders (often associated with seizures) accompany an episodic illness. The treatment of choice is 10 to 12 mg of acyclovir per kilogram given intravenously every 8 hours for 10 to 14 days.
The approach to diagnosis depends on locally available facilities. MRI defines brain lesions earlier in the course than CT and is preferred. PCR to detect herpes simplex viral DNA in CSF is now known to be highly sensitive and specific and should be considered the strategy of choice when herpes simplex encephalitis is considered. Used in patients with various clinical presentations, it has demonstrated a wider spectrum of disease associated with herpes simplex than originally suspected. Empiric therapy with acyclovir is indicated pending results of this study unless alternative diagnoses have been identified. Table 33-4 depicts other treatable diagnoses to consider.
Table 33-4. Treatable diseases that mimic herpes simplex encephalitis
T. gondii is the most common cause of encephalitis in patients with AIDS; such cases most commonly present as mental status changes. The diagnosis is suspected when numerous space-occupying lesions are found in a patient with a CD4 count below 100. Results of tests for serum Toxoplasma antibody are positive in more than 95% of cases; thus, a negative test result suggests alternative diagnoses.
Localized CNS infections may present clinically as mass lesions and be confused with tumors or “strokes.”
Brain abscess is a focal intracerebral collection of pus that often presents as a mass lesion, with focal neurologic defects related to the area involved. Nonspecific headache is often noted, but fever is variable. Mortality has declined in some series to under 10% as a result of earlier diagnosis. Risk factors for mortality and neurologic sequelae include rapid progression and abnormal mental status on presentation. Suspicion of brain abscess necessitates diagnostic CT or MRI with contrast. LP may be hazardous, especially with lesions that impinge on the ventricles. In some series, 15% to 40% of patients with brain abscess die within 24 to 48 hours of diagnostic LP. Evidence of infection, especially in the ear, nose, and throat and cardiopulmonary system, should be carefully sought. However, approximately 20% of patients demonstrate no antecedent focus of infection. Only 10% of patients have positive results on blood cultures.
Causative organisms include most commonly oral anaerobes and other oropharyngeal flora. The importance of S. aureus is controversial, but abscess associated with staphylococcal bacteremia is regularly encountered. Prior antimicrobial therapy may sterilize lesions. Although there have been reports of successful medical management, most authorities recommend drainage of the lesion(s) unless they are inaccessible. CT-guided drainage is now considered the procedure of choice and can be repeated in cases of re-collection or multiple lesions. Materials should be sent for Gram’s stain and culture (aerobic and anaerobic). Length of antibiotic therapy is at least 4 weeks but often should proceed to 6 to 8 weeks; this can be guided by CT response to treatment. Medical therapy alone requires at least 6 to 8 weeks of parenteral treatment. It should be reserved for patients in whom surgery is medically contraindicated or those with numerous or surgically inaccessible lesions. Lesions abutting on ventricles should be drained because of the risk for rupture.
Antimicrobial therapy usually consists of penicillin G (24 million units daily) plus 500 mg of metronidazole three times daily in lieu of chloramphenicol, which had been historically recommended. A third-generation cephalosporin (cefotaxime or ceftriaxone) in full therapeutic doses may be employed instead of penicillin G if considerations include Haemophilus, enteric gram-negative bacilli, or HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) organisms. Specific therapy for other pathogens depends on culture and sensitivity results. For clinically stable patients, much of the treatment can be accomplished through outpatient IV antimicrobial therapy.
The subdural space lies between the dura mater and arachnoid. Infection usually arises as a complication of sinusitis. Less likely origins include otitis media, or surgical or nonsurgical trauma. A male predominance has been noted; the reason is unknown. The presentation may mimic that of brain abscess, although progression from headache with fever to focal (and often extensive) neurologic defects may be rapid and involve an entire cerebral hemisphere. Seizures are common. Enhanced CT or MRI without LP is indicated, and neurosurgical drainage (generally by burr hole) is mandatory.
Antimicrobial therapy is guided by Gram’s stain and culture from drained pus. If the condition is secondary to sinusitis or otitis media, strategies similar to those for brain abscess are reasonable. If it occurs after neurosurgery, coverage of both S. aureus and enteric gram-negative bacilli should be initiated. Suitable treatment alternatives include nafcillin-oxacillin or ceftriaxone plus chloramphenicol or metronidazole in full therapeutic doses pending culture results. The length of therapy is at least 1 month, and this can be guided by repeated imaging studies.
Ruptured Brain Abscess
Brain abscesses may rupture into the ventricular system, resulting in acute purulent meningitis. The patient is critically ill, and mortality approaches 100%. LP may be necessary in this circumstance because meningitis cannot be ruled out. “Meningitis” associated with focal neurologic lesions should prompt suspicion of this condition. Symptoms are those of acute purulent meningitis. Gram’s stain, however, may demonstrate numerous organisms, an unusual observation in other types of meningitis. Therapy consists of high-dose parenteral antimicrobials (based on Gram’s stain results), intensive support, and sometimes neurosurgical intervention. (R.B.B.)
Dill SR, Cobbs CG, McDonald CK. Subdural empyema: analysis of 32 cases and review. Clin Infect Dis 1995;20:372–386.
The authors categorize cases of subdural empyema as secondary to sinusitis, secondary to trauma, or miscellaneous. Sinusitis was the most common cause and was generally associated with streptococci and anaerobes. Cases resulting from trauma (including neurosurgery) were more likely to harbor gram-negative bacilli or S. aureus. Surgical drainage plus at least 1 month of antibiotics is considered appropriate therapy.
Dominiques RB, et al. Evaluation of the range of clinical presentations of herpes simplex encephalitis by using polymerase chain reaction assay of cerebrospinal fluid samples. Clin Infect Dis 1997;25:86–91.
Forty-nine patients with various neurologic presentations were studied with PCR for herpes simplex DNA. These studies demonstrate that in patients with more subtle forms of encephalitis, herpes simplex virus may still be the cause. However, temporal lobe localization is often noted.
Durand ML, et al. Acute bacterial meningitis in adults. N Engl J Med 1993;328:21–28.
This is a review of almost 500 cases of acute bacterial meningitis seen during a 26-year period at a single tertiary-care hospital. S. pneumoniae (37%), N. meningitidis (13%), and L. monocytogenes (10%) were the most common causes of community-acquired disease. Overall, 40% of cases were nosocomial, and enteric gram-negative bacilli were often noted. Recurrent meningitis was seen in 9% of cases and was often associated with CSF leaks. Advanced age, mental status changes on admission, and seizures within 24 hours of admission were adverse prognostic indicators for patients with community-acquired disease. Mortality for this population was 25%.
Lakeman FD, Whitley RJ, the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. J Infect Dis 1995;171:857–863.
This important study documents the role of PCR in identifying herpes simplex viral DNA from CSF. Sensitivity and specificity were 98% and 94%, respectively. Test results were positive in 98% of patients with biopsy-proven herpes simplex encephalitis. The test can be performed on CSF aliquots and obviates the need for brain biopsy in most cases. In cases of encephalitis of undetermined etiology, empiric therapy with acyclovir could be initiated and then discontinued based on the results of this test and clinical response.
Lebel MH, et al. Dexamethasone therapy for bacterial meningitis. N Engl J Med 1988;319:964–971.
Although this investigation was carried out in children, it provides insights into the pathophysiology of bacterial meningitis. The authors present compelling data from two prospective, randomized, double-blinded studies that document the efficacy of dexamethasone (in addition to antimicrobial therapy) in preventing sensorineural hearing loss in children with bacterial meningitis. In most cases, disease was caused by H. influenzae, and other parameters of response (time to become afebrile and CSF indices) were enhanced in the group that received corticosteroids. The results of this study may not be applicable to adults.
Mathisen GE, Johnson JP. Brain abscess. Clin Infect Dis 1997;25:763–781.
The authors review recent literature on the pathophysiology, diagnosis, and treatment of brain abscess. Chloramphenicol is less frequently employed, and most cases can now be treated without craniotomy. CT and MRI have revolutionized the diagnosis of this condition, and CT can generally be used to guide percutaneous drainage. Therapy should be continued for 6 to 8 weeks in most instances, and progress can be documented by radiographic follow-up. Currently, the role of oral antibiotics is limited, but outpatient parenteral antibiotic therapy is valuable once stability has been achieved.
Pegues DA, Carr DB, Hopkins CC. Infectious complications associated with temporary epidural catheters. Clin Infect Dis 1994;19:70–72.
This is one of several articles that deal with the potential for severe infections following the use of catheters for pain control. Risk is related to length of procedure for implantation, and probably to duration of use. Meningitis occurs, often in conjunction with focal muscle or other deep-tissue abscess. Skin flora organisms are most commonly noted, but gram-negative bacilli may also be involved. Therapy consists of drainage, catheter removal, and administration of appropriate antibiotics.
Powers WJ. Cerebrospinal fluid lymphocytosis in acute bacterial meningitis. Am J Med 1985;79:216–220.
The author reviewed the CSF characteristics of 103 cases of acute bacterial meningitis and noted 14 patients in whom more than 50% lymphocytes/monocytes were noted on CSF cell count. Thirty-two percent of patients with fewer than 1,000 cells per cubic millimeter had lymphocytosis. It was associated with pathogens that included S. pneumoniae, N. meningitidis, and H. influenzae. Most cases were in neonates, but lymphocytosis was observed in all age groups.
Quagliarello V, Scheld WM. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med 1992;327:864–872.
This comprehensive review of mechanisms of pathogenesis and pathophysiology in bacterial meningitis explores virulence factors of bacteria, immunology of the CNS, features of the blood–brain barrier, and overall host-bacterial interactions. The authors recommend adjunctive corticosteroid therapy for adults (as well as children) with bacterial meningitis that is associated with positive smears on Gram’s stain (indicative of high organism load), especially if accompanied by evidence of increased intracranial pressure.
Seyjdoux Ch, Francioli P. Bacterial brain abscesses: factors influencing mortality and sequelae. Clin Infect Dis 1992;15:394–401.
The authors retrospectively assess 39 patients with confirmed brain abscess in the CT era to document reasons for mortality and neurologic sequelae. All cases were treated within 24 hours of hospitalization. Risk factors for adverse outcome include mental status changes on admission, neurologic abnormalities on admission, and short duration between first symptoms and presentation (rapid progression). Overall, mortality was 13%, and neurologic sequelae were seen in 22% of survivors.
Talan DA, et al. Role of empiric parenteral antibiotics prior to lumbar puncture in suspected bacterial meningitis: state of the art. Rev Infect Dis 1988;10:365–376.
If LP must be delayed, patients with suspected bacterial meningitis should receive empiric IV antimicrobials. CSF cell count, sugar, and protein determinations are unlikely to be affected, but results of Gram’s stain and culture are less likely to be positive. The authors feel that other studies, such as blood cultures or antigen-detection tests, may still allow a bacteriologic diagnosis.
Tunkel AR, Wispelwey B, Scheld WM. Bacterial meningitis: recent advances in pathophysiology and treatment. Ann Intern Med 1990;112:610–623.
Provides an excellent review of pathophysiologic mechanisms required and responsible for bacterial meningitis. Bacterial virulence factors, the role of the blood–brain barrier, and requirements for antimicrobials used in treatment are reviewed in depth. Several tables are provided with recommendations for antimicrobial use based on patient age and likely pathogens.
Whitley RJ. Viral encephalitis. N Engl J Med 1990;323:242–250.
This represents a recent and concise overview of encephalitis in the United States. Most cases are viral, with pathogenetic mechanisms that include acute, postinfectious, slow-viral, and chronic degenerative disease. Most infections result from either hematogenous or neuronal spread. Herpes simplex viral encephalitis comprises 10% of all cases and is the most amenable to treatment. An excellent table of diseases mimicking herpes simplex encephalitis is provided.
Wolff MA, Young CL, Ramphal R. Antibiotic therapy for Enterobacter meningitis: a retrospective review of 13 episodes and review of the literature. Clin Infect Dis 1993;16:772–777.
The authors appropriately identify problems with the use of cephalosporins in managing Enterobacter meningitis. Treatment with cephalosporins resulted in clinical resistance in 40% of episodes. TMP-SMX, in doses similar to those employed for the management of Pneumocystis carinii pneumonia in AIDS patients, appears to be the agent of choice. Mortality with the use of this agent was lower than that seen with cephalosporins.