The test accurately detects cryptococcal infections more than 95% of the time. Antifungal medicine treats meningitis in those who have it, and can prevent meningitis in those who do not. . Drug acquisition costs are high for antifungal therapies administered for 612 months. Patients with symptoms need treatment. The differential . Michael S. Saag, Richard J. Graybill, Robert A. Larsen, Peter G. Pappas, John R. Perfect, William G. Powderly, Jack D. Sobel, William E. Dismukes, Mycoses Study Group Cryptococcal Subproject, Practice Guidelines for the Management of Cryptococcal Disease, Clinical Infectious Diseases, Volume 30, Issue 4, April 2000, Pages 710718, Benefits and harms. Appropriate antimicrobials should be given promptly if bacterial meningitis is suspected, even if the evaluation is ongoing. In patients with more severe disease, amphotericin B should be used until symptoms are controlled, then an oral azole agent, preferably fluconazole, can be substituted (BIII). Costs. Aggressive management of elevated intracranial pressure is perhaps the most important factor in reducing mortality and minimizing morbidity of acute cryptococcal meningitis. Classic signs of meningeal irritation commonly are absent on physical examination, and routine laboratory assessment is rarely revealing. These patients, as well as those coinfected with human immunodeficiency virus, should be managed in consultation with an infectious disease subspecialist when available. Cookies used to make website functionality more relevant to you. In selected cases, susceptibility testing of the C. neoformans isolate may be beneficial to patient management, particularly if a comparison can be determined between baseline and sequential isolates. Preventing relapse of cryptococcosis reduces mortality and morbidity and slows the progression of HIV disease. Objectives. The desired outcome is resolution of symptoms, such as cough, shortness of breath, sputum production, chest pain, fever, and resolution or stabilization of abnormalities (infiltrates, nodules, masses, etc.) Relapse rates were 2% for fluconazole and 17% for amphotericin B. Vancomycin hydrochloride, alone or in combination with rifampin, may be used if resistant strains of bacteria are identified. The content is unchanged. The desired outcome is resolution of symptoms such as cough, shortness of breath, sputum production, chest pain, fever, and resolution or stabilization of abnormalities (infiltrates, nodules, or masses) on chest radiograph. Chemoprophylaxis of close contacts is helpful in preventing additional infections. Specific recommendations for the treatment of non-HIV-associated cryptococcal meningitis are summarized in table 1. HIV-infected patients with elevated intracranial pressure do not differ clinically from those with normal opening pressure, except that neurological manifestations of disease are more severe among those with higher pressures [21, 22]. Three potential options exist for antifungal maintenance therapy: fluconazole, itraconazole, and weekly or biweekly amphotericin B. Outcomes. Meningitis is an inflammatory process involving the meninges. Copyright 2023 American Academy of Family Physicians. When the CSF pressure is normal for several days, the procedure can be suspended. Systemic complications of acute bacterial meningitis must be treated, including the following: Hypotension or shock Hypoxemia Hyponatremia (from syndrome of inappropriate antidiuretic hormone. After the 2-week period of successful induction therapy, consolidation therapy should be initiated with fluconazole (400 mg orally once daily) administered for 8 weeks or until CSF cultures are sterile [11] (AI). Amphotericin B (0.71 mg/kg given iv daily for 2 weeks) combined with flucytosine, 100 mg/kg given orally in 4 divided doses per day, is the initial treatment of choice [11, 13, 18, 29] (AI). The cause determines if it is contagious. Early, appropriate treatment of HIV-associated cryptococcal meningitis significantly reduces both the morbidity and mortality associated with this disorder. CDC supports various activities to reduce illness and death from cryptococcal meningitis including: CDC has developed training materials to help educate physicians, nurses, HIV/AIDS counselors, pharmacists, and patients about the diagnosis, management, and prevention of cryptococcal disease. Fluconazole should be continued for life. Bacterial meningitis classically has a very high and predominantly neutrophilic pleocytosis, low glucose level, and high protein level. Fluconazole consolidation therapy may be continued for as along as 612 months, depending on the clinical status of the patient. Door-to-antibiotic time lapse of more than six hours has an adjusted odds ratio for mortality of 8.4.37 If CSF results are more consistent with aseptic meningitis, antibiotics can be discontinued, depending on the severity of the presentation and overall clinical picture. If you need to go back and make any changes, you can always do so by going to our Privacy Policy page. The most common forms of immunosuppression other than human immunodeficiency virus (HIV) include glucocorticoid therapy, biologic modifiers, the use of some tyrosine kinase inhibitors (eg, ibrutinib), solid organ transplantation, cancer (particularly hematologic malignancy), and conditions such as . You will be subject to the destination website's privacy policy when you follow the link. Thus, itraconazole should be used in cases where the patient is intolerant of fluconazole or has failed fluconazole therapy (BI). The symptoms of CM usually come on slowly. Abstract. Your Guide to Salmonella Meningitis and How to Spot It, Group B Streptococcal (GBS) Meningitis: Symptoms, Treatment, Outlook, and More. Cryptococcus gattii is a ubiquitous fungal pathogen that causes meningitis and pneumonia. The organism has a strong predilection for infecting the CNS; however, infection has been reported in virtually every organ in the body. Common manifestations in this setting include papilledema, hearing loss, loss of visual acuity, pathological reflexes, severe headache, and abnormal mentation. In cases where flucytosine cannot be administered, amphotericin B alone (administered at the same doses listed above) is an acceptable alternative [13] (BI). CNS disease usually presents as meningitis and on rare occasions as single or multiple focal mass lesions (cryptococcomas). There are 2 key elements in preventing relapse of cryptococcal meningitis: (1) control of HIV replication by means of potent HAART and (2) the use of chronic antifungal therapy to prevent microbial relapse. Aggressive management of elevated intracranial pressure has not been employed consistently in HIV-negative patients with cryptococcal meningitis, and its impact on outcome is unclear. An alternative regimen for AIDS-associated cryptococcal meningitis is amphotericin B (0.71 mg/kg/d) plus 5-flucytosine (100 mg/kg/d) for 610 weeks, followed by fluconazole maintenance therapy. Owing to the intense fungal burden and large amount of replication in patients with HIV disease, adjunctive steroid therapy is not recommended for HIV-infected patients (DIII). Microscopy of cerebrospinal fluid With the advent of polyene antifungal agents, particularly amphotericin B, successful outcomes were achieved in as much as 60%70% of patients with cryptococcal meningitis, depending on the status of the host at the time of presentation [1]. Amphotericin B, flucytosine, and fluconazole are antifungal medications shown to improve survival in patients with cryptococcal infections. Patient information: See related handout on meningitis, written by the authors of this article. Treatment decisions should not be based routinely or exclusively on cryptococcal polysaccharide antigen titers in either the serum or CSF [31, 34] (AI). Recommendations. Meningitis is inflammation of the subarachnoid space, the fluid bathing the brain (between the arachnoid and the pia mater; figure above). The prevalence of cryptococcosis in these studies was too low to provide direct evidence or confirm that antiretroviral therapy affects cryptococcal disease, but there is no biological basis to suspect that control of cryptococcosis in AIDS patients would not be improved by the use of HAART. Options. During the early 1970s, flucytosine was established as an orally bioavailable agent with potent activity against C. neoformans; however, this activity was lost rapidly because of the development of resistance when the drug was used as monotherapy [2]. Drug acquisition costs are high for antifungal therapies administered for life. There are two meningitis vaccines available in the US, and both are proven safe. The Advisory Committee on Immunization Practices recently added a category B recommendation (individual clinical decision making) for consideration of vaccination with serogroup B vaccines in healthy patients 16 to 23 years of age (preferred age of 16 to 18 years).60,61 The serogroup B vaccines are not interchangeable, so care should be taken to ensure completion of the series with the same brand that was used for the initial dose. Treatment with chemoprophylactic antibiotics should be given to close contacts7,62,63 (Table 89,14,6468 ). Cryptococcal meningitis is a common opportunistic infection in AIDS patients, particularly in Southeast Asia and Africa. One-fourth of the patients had opening pressures >350 mm H2O [22]. One large cohort study found a 4.5% mortality rate and a 30.9% rate of complications, such as developmental delay, seizure disorder, or hearing loss, for childhood encephalitis and meningitis combined.50 Tuberculous meningitis also has a higher mortality rate (19.3%) with a higher risk of neurologic disease in survivors (53.9%).51 A recent prospective cohort study also found that males had a higher risk of unfavorable outcomes (odds ratio = 1.34) and death (odds ratio = 1.47).52, Complications from bacterial meningitis also vary by age (Table 71,11,12,46,5356 ). This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. In response to important new evidence that became available in 2021, these new guidelines strongly recommend a single high dose of liposomal amphotericin B as part of the preferred induction regimen for the treatment of cryptococcal meningitis in people . Youll probably switch to taking only fluconazole for about eight weeks. Immunocompetent patients who are asymptomatic and who have a culture of the lung that is positive for C. neoformans may be observed carefully or treated with fluconazole, 200400 mg/d for 36 months [3, 4, 6, 7] (AIII; see article by Sobel [8] for definitions of categories reflecting the strength of each recommendation for or against its use and grades reflecting the quality of evidence on which recommendations are based). This trial was terminated by an independent data safety monitoring board after preliminary results revealed a CSF culture relapse rate of 4% among patients receiving fluconazole (200 mg/d), compared with 24% relapse among itraconazole (200 mg/d) recipients [17]. St George's, University of London. Objectives. Example of Safe Donning and Removal of PPE, U.S. Department of Health & Human Services, Acute diarrhea with a likely infectious cause in an incontinent or diapered patient, Contact Precautions (pediatrics and adult), Droplet Precautions for first 24 hours of antimicrobial therapy; mask and face protection for intubation, Contact Precautions for infants and children, Rash or Exanthems, Generalized, Etiology Unknown, Droplet Precautions for first 24 hours of antimicrobial therapy, Airborne plus Contact Precautions; Contact Precautions only if Herpes simplex, localized zoster in an immunocompetent host or vaccinia viruses most likely, Maculopapular with cough, coryza and fever, Cough/fever/upper lobe pulmonary infiltrate in an HIV-negative patient or a patient at low risk for human immunodeficiency virus (HIV) infection, Airborne Precautions plus Contact precautions, Cough/fever/pulmonary infiltrate in any lung location in an HIV-infected patient or a patient at high risk for HIV infection, Cough/fever/pulmonary infiltrate in any lung location in a patient with a history of recent travel (10-21 days) to countries with active outbreaks of SARS, avian influenza, Respiratory infections, particularly bronchiolitis and pneumonia, in infants and young children. Ketoconazole is not effective as maintenance therapy [30] (DII). Elevated intracranial pressure is defined as opening pressure >200 mm H2O, measured with the patient in a reclining (lateral decubitus) position. Benefits and harms. It is clear that all HIV-infected patients require treatment, since they are at high risk for disseminated infection. Toxic side effects of amphotericin B are common and include nausea, vomiting, chills, fever, and rigors, which can occur with each dose. CSF results can be variable, and decisions about treatment with antibiotics while awaiting culture results can be challenging. Induction therapy. A fungus called C. neoformans causes most cases of CM. However, cryptococcal meningitis is still a major problem where HIV prevalence is high and where access to healthcare may be limited. Owing to its inherent toxicity and difficulty of administration, this therapy is recommended only in this salvage setting [14] (CII). Recommendations. Cryptococcal meningitis specifically occurs after Cryptococcus has spread from the lungs to the brain. You can review and change the way we collect information below. Bacterial meningitis is a medical emergency that requires prompt recognition and treatment. You can learn more about how we ensure our content is accurate and current by reading our. Delayed initiation of antibiotics can worsen mortality. Your doctor may also test your blood. The toxicity of amphotericin B limits its utility as a desired agent in the treatment of mild-to-moderate pulmonary disease among immunocompetent hosts. By this definition, almost three-fourths of 221 HIV-infected patients in a recent NIAID-sponsored Mycoses Study Group trial had elevated intracranial pressure at baseline. Although all asymptomatic patients with positive cultures should be considered for treatment, many immunocompetent patients with positive sputum cultures have done well without therapy [5]. Costs. Droplet Precautions plus Contact Precautions, with face/eye protection, emphasizing safety sharps and barrier precautions when blood exposure likely. Viral meningitis (non-HSV) management is focused on supportive care. Add Droplet Precautions for the first 24 hours of appropriate antimicrobial therapy if invasive Group A streptococcal disease is suspected, Centers for Disease Control and Prevention. Elevated intracranial pressure is an important contributor to morbidity and mortality of cryptococcal meningitis. Costs. Treatment options for cryptococcal disease in HIV-infected patients. According to the U.S. Centers for Disease Control and Prevention (CDC), infections by C. neoformans occur yearly in about 0.4 to 1.3 cases per 100,000 people in the general healthy population. Latent Tuberculosis Infection Treatment: Still a Long Road Ahead, A Systematic Review and Meta-Analysis of Tuberculous Preventative Therapy Adverse Events, Efficacy of a 4-Antigen Staphylococcus aureus Vaccine in Spinal Surgery: The STRIVE Randomized Clinical Trial, Durlobactam, a Broad-Spectrum Serine -lactamase Inhibitor, Restores Sulbactam Activity Against Acinetobacter Species, The Pharmacokinetics/Pharmacodynamic Relationship of Durlobactam in Combination With Sulbactam in In Vitro and In Vivo Infection Model Systems Versus Acinetobacter baumannii-calcoaceticus Complex, Mycoses Study Group Cryptococcal Subproject, About the Infectious Diseases Society of America, Guidelines for the Treatment of Cryptococcosis in Patients without HIV Infection, Guidelines for the Treatment of Pulmonary and CNS Cryptococcosis in Patients with HIV Infection, Guidelines from the Infectious Diseases Society of America, Receive exclusive offers and updates from Oxford Academic, Antifungal Therapy and Management of Complications of Cryptococcosis due to, Identification of Patients with Acute AIDS-Associated Cryptococcal Meningitis Who Can Be Effectively Treated with Fluconazole: The Role of Antifungal Susceptibility Testing, Early Mycological Treatment Failure in AIDS-Associated Cryptococcal Meningitis. As a result, most clinicians are uncertain about which agents to use for which underlying disease state, in what combination, and for what duration. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. A lab will test this fluid to find out if you have CM. HIV-negative, immunocompromised hosts should be treated in the same fashion as those with CNS disease, regardless of the site of involvement. If you need to go back and make any changes, you can always do so by going to our Privacy Policy page. As the overall incidence of cryptococcal disease has increased so has the number of treatment options available to treat the disease. CSF antigen titers are higher and the India ink smear is more frequently positive among patients with elevated opening pressure than among patients with normal opening pressure. This combination helps treat the condition quicker. U.S. Centers for Disease Control and Prevention (CDC),,,,, Bacterial, Viral, and Fungal Meningitis: Learn the Difference, Recurrent Meningitis: A Rare but Serious Condition, Understanding the Meningitis Vaccine: What It Is and When You Need It. Theyll look for the symptoms associated with this disease. People with advanced HIV should be tested early for cryptococcal infection. Fluconazole (400800 mg/d) plus flucytosine (100150 mg/kg/d) for 6 weeks is an alternative to the use of amphotericin B, although toxicity with this regimen is high. Serum procalcitonin, serum C-reactive protein, and CSF lactate levels can be useful in distinguishing between aseptic and bacterial meningitis.2833 C-reactive protein has a high negative predictive value but a much lower positive predictive value.28 Procalcitonin is sensitive (96%) and specific (89% to 98%) for bacterial causes of meningitis.29,30 CSF lactate also has a high sensitivity (93% to 97%) and specificity (92% to 96%).3133 CSF latex agglutination testing for common bacterial pathogens is rapid and, if positive, can be useful in patients with negative Gram stain if LP was performed after antibiotics were administered. Aseptic meningitis is the most common form. Search dates: October 1, 2016, and March 13, 2017. Three percent of fluconazole patients and 37% of placebo patients relapsed at any site. Prospective clinical trials and carefully conducted observational studies show that potent antiretroviral therapy reduces the incidence of opportunistic infections [2527]. Owing to its inherent toxicity and difficulty of administration, it is recommended only in a salvage setting [14] (CII). Measuring stigma associated with hepatitis B virus infection in Sierra Leone: Validation of an abridged Berger HIV stigma scale. INTRODUCTION. Optimal initial management with amphotericin and flucytosine improves survival against alternative therapies, although amphotericin is difficult to administer and flucytosine is not available in middle or low income countries, where cryptococcal meningitis is most prevalent. It is notable that, despite the relatively short time AIDS has been in existence, more data now exist on the treatment of AIDS-associated cryptococcal meningitis than on the treatment of any other form of cryptococcal infection. Patients with a positive culture at 2 weeks may require a longer course of induction therapy. Most people who develop CM already have severely compromised immune systems. In addition, the Infectious Diseases Society of America, the National Institute for Health and Care Excellence, and the American Academy of Pediatrics guidelines were reviewed. The choice of treatment for disease caused by Cryptococcus neoformans depends on both the anatomic sites of involvement and the host's immune status. The goal of treatment is control of the infection and prevention of dissemination of disease to the CNS. The clinicians index of suspicion should be guided by the prevalence of specific conditions in the community, as well as clinical judgment. Additional costs are accrued for monthly monitoring of therapies associated with most of the recommended regimens. Sputum fungal culture, blood fungal culture, and a serum cryptococcal antigen test are appropriate laboratory studies in any HIV-infected patient with pneumonia and a CD4+ T lymphocyte count <200 cells/mL. Youll probably also take flucytosine, another antifungal medication, while youre taking the amphotericin B. Despite the absence of controlled clinical trial data from HIV-negative populations of patients, a frequently used alternative treatment for cryptococcal meningitis in immunocompetent patients is an induction course of amphotericin B (0.51 mg/kg/d) with flucytosine (100 mg/kg/d) for 2 weeks, followed by consolidation therapy with fluconazole (400 mg/d) for an additional 810 weeks [7] (BIII). Cryptococcal meningitis is a fungal infection of the tissues covering the brain and spinal cord. Surgery should be considered for patients with persistent or refractory pulmonary or bone lesions. Pilot studies that have investigated fluconazole with flucytosine as initial therapy yielded unsatisfactory outcomes [7]. Dexamethasone in Cryptococcal Meningitis N Engl J Med. Drug acquisition costs are high for antifungal therapies administered for life. When flucytosine was added to amphotericin B as combination therapy, overall outcome of therapy was improved and the duration of treatment could be reduced from 10 weeks to 46 weeks, depending on the status of the host [1, 3]. In addition, the test doesnt require costly laboratory equipment and expertise, making it ideal for low-resource settings. To treat a Cryptococcus infection, doctors may use any of the following antifungal medications: amphotericin B (Fungizone) flucytosine (Ancobon) fluconazole (Diflucan) For a Histoplasma infection,. Before 1950, disseminated cryptococcal disease was uniformly fatal. The most troublesome toxic side effect is renal injury, including elevation of the serum creatinine, hypokalemia, hypomagnesemia, and renal tubular acidosis. This was demonstrated in a placebo-controlled, double-blind, randomized trial evaluating the effectiveness of fluconazole for maintenance therapy after successful primary treatment with either amphotericin B alone or in combination with flucytosine in patients with AIDS [23]. All information these cookies collect is aggregated and therefore anonymous. Patients typically present with fever and/or headache of gradual onset, which becomes progressively more debilitating. Aseptic meningitis is the most common form of meningitis with an annual incidence of 7.6 per 100,000 adults. Cryptococcal meningitis. Lateral flow assay is a reliable, rapid, and inexpensive test that can be used on a small sample of blood or spinal fluid to detect cryptococcal antigen. Some HIV-infected patients present with isolated cryptococcemia or a positive serum cryptococcal antigen titer (>1 : 8) without evidence of clinical disease. An 8-person subcommittee of the National Institute of Allergy and Infectious Diseases (NIAID) Mycoses Study Group evaluated available data on the treatment of cryptococcal disease. This test cannot be used to rule out bacterial meningitis.7. Early, appropriate treatment of non-CNS pulmonary and extrapulmonary cryptococcosis reduces morbidity and prevents progression to potentially life-threatening CNS disease. Cryptococcus neoformans is a fungus that lives in the environment throughout the world. CM usually occurs in people who have a compromised immune system. Occasionally patients who present with extremely high opening pressures (>400 mm H2O) may require a lumbar drain, especially when frequent lumbar punctures are required to or fail to control symptoms of elevated intracranial pressure. However, this is not possible in many areas of high incidence, and it should not delay diagnosis. An alternative to this regimen is amphotericin B (0.71 mg/kg/d) plus 5-flucytosine (100 mg/kg/d) for 2 weeks, followed by fluconazole (400 mg/day) for a minimum of 10 weeks. See additional information. Yet, because of the potentially grave consequences of overlooking this illness, it is imperative to assess AIDS patients with pneumonia for possible fungal infection. In contrast to non-CNS disease, several studies have been performed that specifically evaluate outcomes among HIV-negative patients with cryptococcal meningitis. These cookies may also be used for advertising purposes by these third parties. Toxicity associated with use of fluconazole/flucytosine combination therapy is substantial [15]. Maintain isolation precautions as necessary with bacterial meningitis. Several treatment options exist for managing elevated intracranial pressure (table 3) including intermittent CSF drainage by means of sequential lumbar punctures, insertion of a lumbar drain, or placement of a ventriculoperitoneal shunt. As is true for other systemic mycoses, treatment of disease due to C. neoformans have improved dramatically over the last 2 decades. Itraconazole appears less active than fluconazole [17, 33]. Intravenous antibiotics should be used to complete the full treatment course, but outpatient management can be considered in persons who are clinically improving after at least six days of therapy with reliable outpatient arrangements (i.e., intravenous access, home health care, reliable follow-up, and a safe home environment).7, Corticosteroids are traditionally used as adjunctive treatment in meningitis to reduce the inflammatory response. Fever, headache, neck stiffness, and altered mental status are classic symptoms of meningitis, and a combination of two of these occurs in 95% of adults presenting with bacterial meningitis.12 However, less than one-half of patients present with all of these symptoms.12,13, Presentation varies with age. Introduction: Cryptococcal Meningitis (CM) remains a high-risk clinical condition, and many patients require emergency department (ED) management for complications and stabilization. Dexamethasone should be administered to children and adults with suspected bacterial meningitis before or at the time of initiation of antibiotics. Mortality remains high despite the introduction of vaccinations for common pathogens that have reduced the incidence of meningitis worldwide. Learn how it can, Recurrent meningitis is a rare condition that happens when meningitis goes away and comes back again. These cases are often viral, and enterovirus is the most common pathogen in immunocompetent individuals.2,4 The most common etiology in U.S. adults hospitalized for meningitis is enterovirus (50.9%), followed by unknown etiology (18.7%), bacterial (13.9%), herpes simplex virus (HSV; 8.3%), noninfectious (3.5%), fungal (2.7%), arboviruses (1.1%), and other viruses (0.8%).5 Enterovirus and mosquito-borne viruses, such as St. Louis encephalitis and West Nile virus, often present in the summer and early fall.4,6 HSV and varicella zoster virus can cause meningitis and encephalitis.2, Causative bacteria in community-acquired bacterial meningitis vary depending on age, vaccination status, and recent trauma or instrumentation7,8 (Table 29 ). Durable Viral Suppression Among Young Adults Living with HIV Receiving Ryan White Services in New York City. Options. Routine studies should include the following: measurement of CSF opening pressure (with the patient in the lateral recumbent position); collection of sufficient CSF for fungal culture (3 mL); and the measurement of CSF cryptococcal antigen titer, glucose level, protein level, and cell count with differential (5 mL total). Let's discuss when to get it and possible side effects: Learn how COVID-19 could lead to meningitis in rare cases and what it may mean for your treatment and outlook. If you do not allow these cookies we will not know when you have visited our site, and will not be able to monitor its performance. In infants and young children, the presentation is often nonspecific. on chest radiograph. Cookies used to enable you to share pages and content that you find interesting on through third party social networking and other websites. Patients should initially undergo daily lumbar punctures to maintain CSF opening pressure in the normal range. Diagnosis is clinical and microscopic, confirmed by culture or fixed . Patients with the syndromes or conditions listed below may present with atypical signs or symptoms (e.g.neonates and adults with pertussis may not have paroxysmal or severe cough). However, failing eradication, which is common in HIV disease, long-term control of infection and resolution of clinical evidence of disease are the principal goals. Cookies used to track the effectiveness of CDC public health campaigns through clickthrough data. Its usually found in soil that contains bird droppings. Some of the treatment regimens currently in use have not been studied in randomized clinical trials, but rather are used on the basis of anecdotal reports or open-label phase II studies. Among patients with normal baseline opening pressure (<200 mm H2O), a repeat lumbar puncture should be performed 2 weeks after initiation of therapy to exclude elevated pressure and to evaluate culture status. All patients should be monitored closely for evidence of elevated intracranial pressure and managed in a fashion similar to HIV-positive patients (see below). CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. In the most recent large comparative study of this disease, the overall mortality was 6%; in contrast, previous treatment studies experienced mortality rates of 14%25% [11, 13].