Infectious Diseases Society of America Guidelines on Healthcare-Associated Ventriculitis and Meningitis

Diagnosis

IDSA guidelines on the diagnosis of healthcare-associated ventriculitis and meningitis are as follows^[60]:

New headache, fever, evidence of meningeal irritation, seizures, and/or worsening mental status suggest ventriculitis or meningitis in the setting of recent trauma or neurosurgery.
Fever, in the absence of another clear source of infection, suggests CNS infection in the setting of recent head trauma or neurosurgery.
New headache, nausea, lethargy, and/or change in mental status suggest CSF shunt infection.
Erythema and tenderness over the subcutaneous shunt tubing suggest CSF shunt infection.
Symptoms and signs of peritonitis or abdominal tenderness in patients with ventriculoperitoneal shunts, in the absence of another clear etiology, indicate CSF shunt infection.
Demonstration of bacteremia in a patient with a ventriculoatrial shunt, in the absence of another clear source of bacteremia, is evidence of CSF shunt infection.
Symptoms and signs of pleuritis in patients with ventriculopleural shunts, in the absence of another clear etiology, indicate CSF shunt infection.
Single or multiple positive CSF culture results in patients with CSF pleocytosis and/or hypoglycorrhachia, or an increasing cell count, and clinical symptoms suspicious for ventriculitis or meningitis, indicates CSF drain infection.
CSF cultures are the most important test to establish the diagnosis of healthcare-associated ventriculitis and meningitis.
If initial CSF culture results are negative in patients with CSF shunts or drains with suspected infection, cultures should be held for at least 10 days in an attempt to identify organisms such as P acnes.
Blood cultures are recommended in patients with suspected ventriculoatrial shunt infections.
CSF and blood cultures in selected patients should be obtained before the administration of antimicrobial therapy; a negative CSF culture result in the setting of previous antimicrobial therapy does not exclude healthcare-associated ventriculitis and meningitis.
CSF pleocytosis with a positive culture result and symptoms of infection indicate a diagnosis of healthcare-associated ventriculitis or meningitis.
CSF cultures that grow S aureus or aerobic gram-negative bacilli indicate infection.
CSF cultures that grow a fungal pathogen indicate infection.
Neuroimaging is recommended in patients with suspected healthcare-associated ventriculitis and meningitis.
MRI with gadolinium enhancement and diffusion-weighted imaging is recommended for detecting abnormalities in patients with healthcare-associated ventriculitis and meningitis.
In patients with infected ventriculoperitoneal shunts and abdominal symptoms (eg, pain or tenderness), ultrasonography or CT scanning of the abdomen is recommended to detect CSF loculations at the shunt terminus.

Treatment

IDSA guidelines on the treatment of healthcare-associated ventriculitis and meningitis are as follows^[60]:

Vancomycin plus an anti-pseudomonal beta-lactam (eg, cefepime, ceftazidime, or meropenem) is recommended as empiric therapy for healthcare-associated ventriculitis and meningitis; the choice of empiric beta-lactam agent should be based on local in vitro susceptibility patterns.
In seriously ill adult patients with healthcare-associated ventriculitis and meningitis, the vancomycin trough concentration should be maintained at 15-20 μg/mL in those who receive intermittent bolus administration.
For patients with healthcare-associated ventriculitis and meningitis who have experienced anaphylaxis to beta-lactam antimicrobial agents and in whom meropenem is contraindicated, aztreonam or ciprofloxacin is recommended for gram-negative coverage.
For treatment of infection caused by methicillin-susceptible S aureus (MSSA), nafcillin or oxacillin is recommended. If the patient cannot receive beta-lactam agents, the patient can be desensitized or may receive vancomycin as an alternative agent.
For treatment of infection caused by methicillin-resistant S aureus (MRSA), vancomycin is recommended as first-line therapy, with consideration for an alternative antimicrobial agent if the vancomycin minimal inhibitory concentration (MIC) is ≥1 μg/mL.
Infections caused by S aureus or gram-negative bacilli with or without significant CSF pleocytosis, CSF hypoglycorrhachia, or clinical symptoms or systemic features should be treated for 10-14 days (strong, low); some experts suggest treatment of infection caused by gram-negative bacilli for 21 days.
For treatment of infection caused by coagulase-negative staphylococci, the recommended therapy should be similar to that for S aureus and based on in vitro susceptibility testing.
Rifampin is recommended as part of combination therapy for any patient with intracranial or spinal hardware such as a CSF shunt or drain.
For treatment of patients with healthcare-associated ventriculitis and meningitis caused by staphylococci in whom beta-lactam agents or vancomycin cannot be used, linezolid, daptomycin, or trimethoprim-sulfamethoxazole is recommended, with selection of a specific agent based on in vitro susceptibility testing.
For treatment of infection caused by P acnes, penicillin G is recommended.
Infections caused by a coagulase-negative Staphylococcus or P acnes with no or minimal CSF pleocytosis, normal CSF glucose, and few clinical symptoms or systemic features should be treated for 10 days.
Infections caused by a coagulase-negative Staphylococcus or P acnes with significant CSF pleocytosis, CSF hypoglycorrhachia, or clinical symptoms or systemic features should be treated for 10-14 days.
For treatment of infection caused by gram-negative bacilli susceptible to third-generation cephalosporins, ceftriaxone or cefotaxime is recommended.
For treatment of infection caused by Pseudomonas species, the recommended therapy is cefepime, ceftazidime, or meropenem; recommended alternative antimicrobial agents are aztreonam or a fluoroquinolone with in vitro activity.
For treatment of infection caused by Acinetobacter species, meropenem is recommended; for strains that demonstrate carbapenem resistance, colistimethate sodium or polymyxin B (either agent administered by the intravenous and intraventricular routes) is recommended.
Prolonged infusion of meropenem (each dose administered over 3 hours) may be successful in treating resistant gram-negative organisms.
For treatment of infection caused by Candida species, based on in vitro susceptibility testing, liposomal amphotericin B, often combined with 5-flucytosine, is recommended; once the patient shows clinical improvement, therapy can be changed to fluconazole if the isolated species is susceptible.
For treatment of infection caused by Aspergillus or Exserohilum species, voriconazole is recommended.
When antimicrobial therapy is administered via a ventricular drain, the drain should be clamped for 15-60 minutes to allow the agent to equilibrate throughout the CSF.
Dosages and intervals of intraventricular antimicrobial therapy should be adjusted based on CSF antimicrobial concentrations to 10-20 times the MIC of the causative microorganism, ventricular size, and daily output from the ventricular drain.
In patients with repeatedly positive CSF cultures on appropriate antimicrobial therapy, treatment should be continued for 10-14 days after the last positive culture.

Medication

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Media Gallery

Pneumococcal meningitis in a patient with alcoholism. Courtesy of the CDC/Dr. Edwin P. Ewing, Jr.
Acute bacterial meningitis. This axial nonenhanced computed tomography scan shows mild ventriculomegaly and sulcal effacement.
Acute bacterial meningitis. This axial T2-weighted magnetic resonance image shows only mild ventriculomegaly.
Acute bacterial meningitis. This contrast-enhanced, axial T1-weighted magnetic resonance image shows leptomeningeal enhancement (arrows).
Chronic mastoiditis and epidural empyema in a patient with bacterial meningitis. This axial computed tomography scan shows sclerosis of the temporal bone (chronic mastoiditis), an adjacent epidural empyema with marked dural enhancement (arrow), and the absence of left mastoid air.
Subdural empyema and arterial infarct in a patient with bacterial meningitis. This contrast-enhanced axial computed tomography scan shows left-sided parenchymal hypoattenuation in the middle cerebral artery territory, with marked herniation and a prominent subdural empyema.

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Table 1. Most Common Bacterial Pathogens on Basis of Age and Predisposing Risks

Risk or Predisposing Factor	Bacterial Pathogen
Age 0-4 weeks	Streptococcus agalactiae (GBS) Escherichia coli K1 Listeria monocytogenes
Age 4-12 weeks	S agalactiae E coli Haemophilus influenzae Streptococcus pneumoniae Neisseria meningitidis
Age 3 months to 18 years	N meningitidis S pneumoniae H influenzae
Age 18-50 years	S pneumoniae N meningitidis H influenzae
Age >50 years	S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli
Immunocompromised state	S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli
Intracranial manipulation, including neurosurgery	Staphylococcus aureus Coagulase-negative staphylococci Aerobic gram-negative bacilli, including Pseudomonas aeruginosa
Basilar skull fracture	S pneumoniae H influenzae Group A streptococci
CSF shunts	Coagulase-negative staphylococci S aureus Aerobic gram-negative bacilli Propionibacterium acnes
CSF = cerebrospinal fluid; GBS = group B streptococcus.

Table 2. Infectious Agents Causing Aseptic Meningitis

Category	Agent
Bacteria	Partially treated bacterial meningitis Listeria monocytogenes Brucella spp Rickettsia rickettsii Ehrlichia spp Mycoplasma pneumoniae Borrelia burgdorferi Treponema pallidum Leptospira spp Mycobacterium tuberculosis Nocardia spp
Parasites	Naegleria fowleri Acanthamoeba spp Balamuthia spp Angiostrongylus cantonensis Gnathostoma spinigerum Baylisascaris procyonis Strongyloides stercoralis Taenia solium (cysticercosis) Toxocara spp
Fungi	Cryptococcus neoformans Coccidioides immitis Blastomyces dermatitidis Histoplasma capsulatum Candida spp Aspergillus spp
Viruses	Enterovirus	Poliovirus Echovirus Coxsackievirus A Coxsackievirus B Enterovirus 68-71
	Herpesvirus (HSV)	HSV-1 and HSV-2 Varicella-zoster virus Epstein-Barr virus Cytomegalovirus HHV-6 and HHV-7
	Paramyxovirus	Mumps virus Measles virus
	Togavirus	Rubella virus
	Flavivirus	West Nile virus Japanese encephalitis virus St Louis encephalitis virus
	Bunyavirus	California encephalitis virus La Crosse encephalitis virus
	Alphavirus	Eastern equine encephalitis virus Western equine encephalitis virus Venezuelan encephalitis virus
	Reovirus	Colorado tick fever virus
	Arenavirus		LCM virus
	Rhabdovirus		Rabies virus
	Retrovirus		HIV
HHV = human herpesvirus; HSV = herpes simplex virus; LCM = lymphocytic choriomeningitis.

Table 3. Causes of Chronic Meningitis

Category	Agent
Bacteria	Mycobacterium tuberculosis Borrelia burgdorferi Treponema pallidum Brucella spp Francisella tularensis Nocardia spp Actinomyces spp
Fungi	Cryptococcus neoformans Coccidioides immitis Blastomyces dermatitidis Histoplasma capsulatum Candida albicans Aspergillus spp Sporothrix schenckii
Parasites	Acanthamoeba spp Naegleria fowleri Angiostrongylus cantonensis Gnathostoma spinigerum Baylisascarisprocyonis Schistosoma spp Strongyloides stercoralis Echinococcus granulosus

Table 4. Changing Epidemiology of Acute Bacterial Meningitis in United States*

Bacteria	1978-1981	1986	1995	1998-2007
Haemophilus influenzae	48%	45%	7%	6.7%
Listeria monocytogenes	2%	3%	8%	3.4%
Neisseria meningitidis	20%	14%	25%	13.9%
Streptococcus agalactiae (group B streptococcus)	3%	6%	12%	18.1%
Streptococcus pneumoniae	13%	18%	47%	58%
*Nosocomial meningitis is not included; these data include only the 5 major meningeal pathogens.

Other Exposures and Organisms Associated with Meningitis

Animal exposure	Organism associated with meningitis
Dog	Brucella B henselae C canimorus C cynodegmi Leptospira M avium P multocida Rabies
Cat	B henselae C canimorsus C cynodegmi M avium P multocida
Cow	B anthracis Brucella C fetus C burnetii Leptospira M bovis
Sheep	Brucella C fetus C burnetii
Pig	Brucella Leptospira M avium M bovis P multocida S suis
Goat	Brucella C fetus C burnetiid S equi
Horse	Leptospira M avium S equi
Rabbits/squirrel	F tularensis Leptospira M avium Yersinia pestis
Fish	Streptococcus iniae
Rodents (hamster, rats, mice)	Lymphocytic choriomeningitis virus
Mosquito	Yellow fever Plasmodium sp ( Malaria ) Japanese encephalitis West Nile Virus St Louis California encephalitis group of viruses Dengue virus Chikungunya virus Zika virus
Bats	Rabies Australian Bat Lyssavirus Nipah Virus
Ticks	Borrelia burgdorferi (Lyme’s disease) Ehrlichia Rocky Mountain spotted fever Anaplasma Powassan virus Coltivirus (Colarado tick fever)
Sandflies	Toscana virus

Table 6. CSF Findings in Meningitis by Etiologic Agent

Agent	Opening Pressure (mm H₂O)	WBC count (cells/µL)	Glucose (mg/dL)	Protein (mg/dL)	Microbiology
Bacterial meningitis	200-300	100-5000; >80% PMNs	< 40	>100	Specific pathogen demonstrated in 60% of Gram stains and 80% of cultures
Viral meningitis	90-200	10-300; lymphocytes	Normal, reduced in LCM and mumps	Normal but may be slightly elevated	Viral isolation, PCR assays
Tuberculous meningitis	180-300	100-500; lymphocytes	Reduced, < 40	Elevated, >100	Acid-fast bacillus stain, culture, PCR
Cryptococcal meningitis	180-300	10-200; lymphocytes	Reduced	50-200	India ink, cryptococcal antigen, culture
Aseptic meningitis	90-200	10-300; lymphocytes	Normal	Normal but may be slightly elevated	Negative findings on workup
Normal values	80-200	0-5; lymphocytes	50-75	15-40	Negative findings on workup
LCM = lymphocytic choriomeningitis; PCR = polymerase chain reaction; PMN = polymorphonuclear leukocyte; WBC = white blood cell.

Table 7. Comparison of CSF Findings by Type of Organism

Normal Finding	Bacterial Meningitis	Viral Meningitis*	Fungal Meningitis**
Pressure (mm H₂O) 50-150	Increased	Normal or mildly increased	Normal or mildly increased in tuberculous meningitis; may be increased in fungal; AIDS patients with cryptococcal meningitis have increased risk of blindness and death unless kept below 300 mm H₂O
Cell count (mononuclear cells/µL) Preterm: 0-25 Term: 0-22 >6 months: 0-5	No cell count result can exclude bacterial meningitis; PMN count typically in 1000s but may be less dramatic or even normal (classically, in very early meningococcal meningitis and in extremely ill neonates); lymphocytosis with normal CSF chemistries seen in 15-25%, especially when cell counts < 1000 or with partial treatment; ~90% of patients with ventriculoperitoneal shunts who have CSF WBC count >100 are infected; CSF glucose is usually normal, and organisms are less pathogenic; cell count and chemistries normalize slowly (over days) with antibiotics	Cell count usually < 500, nearly 100% mononuclear; up to 48 hours, significant PMN pleocytosis may be indistinguishable from early bacterial meningitis; this is particularly true with eastern equine encephalitis; presence of nontraumatic RBCs in 80% of HSV meningoencephalitis, though 10% have normal CSF results	Hundreds of mononuclear cells
Microscopy No organisms	Gram stain 80% sensitive; inadequate decolorization may mistake Haemophilus influenzae for gram-positive cocci; pretreatment with antibiotics may affect stain uptake, causing gram-positive organisms to appear gram-negative and decrease culture yield by average of 20%	No organism	India ink is 50% sensitive for fungi; cryptococcal antigen is 95% sensitive; AFB stain is 40% sensitive for tuberculosis (increase yield by staining supernatant from at least 5 mL CSF)
Glucose Euglycemia: >50% serum Hyperglycemia: >30% serum Wait 4 hr after glucose load	Decreased	Normal	Sometimes decreased; aside from fulminant bacterial meningitis, lowest levels of CSF glucose are seen in tuberculous meningitis, primary amebic meningoencephalitis, and neurocysticercosis
Protein (mg/dL) Preterm: 65-150 Term: 20-170 >6 months: 15-45	Usually >150, may be >1000	Mildly increased	Increased; >1000 with relatively benign clinical presentation suggestive of fungal disease
AFB = acid-fast bacillus; CSF = cerebrospinal fluid; HSV = herpes simplex virus; RBC = red blood cell; PMN = polymorphonuclear leukocyte. Some bacteria (eg, Mycoplasma, Listeria, Leptospira spp, Borrelia burgdorferi [Lyme], and spirochetes) produce spinal fluid alterations that resemble the viral profile. An aseptic profile also is typical of partially treated bacterial infections (>33% of patients have received antimicrobial treatment, especially children) and the 2 most common causes of encephalitis—the potentially curable HSV and arboviruses. *In contrast, tuberculous meningitis and parasites resemble the fungal profile more closely.

Table 7. Recommended Empiric Antibiotics for Suspected Bacterial Meningitis, According to Age or Predisposing Factors ^[40]

Age or Predisposing Feature	Antibiotics
Age 0-4 wk	Ampicillin plus either cefotaxime or an aminoglycoside
Age 1 mo-50 y	Vancomycin plus cefotaxime or ceftriaxone*
Age >50 y	Vancomycin plus ampicillin plus ceftriaxone or cefotaxime plus vancomycin*
Impaired cellular immunity	Vancomycin plus ampicillin plus either cefepime or meropenem
Recurrent meningitis	Vancomycin plus cefotaxime or ceftriaxone
Basilar skull fracture	Vancomycin plus cefotaxime or ceftriaxone
Head trauma, neurosurgery, or CSF shunt	Vancomycin plus ceftazidime, cefepime, or meropenem
CSF = cerebrospinal fluid. Add ampicillin if Listeria monocytogenes* is a suspected pathogen.

Table 8. Specific Antibiotics and Duration of Therapy for Acute Bacterial Meningitis

Bacteria	Susceptibility	Antibiotic(s)	Duration (days)
Streptococcus pneumoniae	Penicillin MIC ≤0.06 μg/mL	Recommended: Penicillin G or ampicillin Alternatives: Cefotaxime, ceftriaxone, chloramphenicol	10-14
	Penicillin MIC ≥0.12 μg/mL Cefotaxime or ceftriaxone MIC ≥0.12 μg/mL	Recommended: Cefotaxime or ceftriaxone Alternatives: Cefepime, meropenem
	Cefotaxime or ceftriaxone MIC ≥1.0 μg/mL	Recommended: Vancomycin plus cefotaxime or ceftriaxone Alternatives: Vancomycin plus moxifloxacin
Haemophilus influenzae	Beta-lactamase−negative	Recommended: Ampicillin Alternatives: Cefotaxime, ceftriaxone, cefepime, chloramphenicol, aztreonam, a fluoroquinolone	7
	Beta-lactamase−positive	Recommended: Cefotaxime or ceftriaxone Alternatives: Cefepime, chloramphenicol, aztreonam, a fluoroquinolone
	Beta-lactamase−negative, ampicillin-resistant	Recommended: Meropenem Alternatives: Cefepime, chloramphenicol, aztreonam, a fluoroquinolone
Neisseria meningitidis	Penicillin MIC < 0.1 μg/mL	Recommended: Penicillin G or ampicillin Alternatives: Cefotaxime, ceftriaxone, chloramphenicol	7
Neisseria meningitidis	Penicillin MIC ≥0.1 μg/mL	Recommended: Cefotaxime or ceftriaxone Alternatives: Cefepime, chloramphenicol, a fluoroquinolone, meropenem	7
Listeria monocytogenes	...	Recommended: Ampicillin or penicillin G Alternative: TMP-SMX	14-21
Streptococcus agalactiae	...	Recommended: Ampicillin or penicillin G Alternatives: Cefotaxime, ceftriaxone, vancomycin	14-21
Enterobacteriaceae	...	Recommended: Cefotaxime or ceftriaxone Alternatives: Aztreonam, a fluoroquinolone, TMP-SMX, meropenem, ampicillin	21
Pseudomonas aeruginosa	...	Recommended: Ceftazidime or cefepime Alternatives: Aztreonam, meropenem, ciprofloxacin	21
Staphylococcus epidermidis		Recommended: Vancomycin Alternative: Linezolid Consider addition of rifampin
MIC= minimal inhibitory concentration; TMP-SMX = trimethoprim-sulfamethoxazole.

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Author

Shikha S Vasudeva, MBBS Assistant Professor of Internal Medicine, Virginia Tech Carilion School of Medicine; Assistant Professor of Internal Medicine, Edward Via Virginia College of Osteopathic Medicine; Infectious Disease Consultant, Department of Medicine, Veterans Affair Medical Center

Shikha S Vasudeva, MBBS is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Rodrigo Hasbun, MD, MPH Associate Professor of Medicine, Section of Infectious Diseases, University of Texas Medical School at Houston

Disclosure: Received research grant from: Biofire<br/> Speaker for Biofire.

Acknowledgements

Suur Biliciler, MD Neuromuscular Fellow, Department of Neurology, Baylor College of Medicine