Physicians' Press - Innovative Medical Publishing - Antibiotic Essentials Self Assessment & Review

a.    Neisseria meningitidis
b.    Hemophilus influenzae
c.    Streptococcus pneumoniae
d.    Staphylococcus aureus
e.    Escherichia coli

Answer: More than 80% of community-acquired acute bacterial meningitis (ABM) in the United States is caused by three pathogens—Neisseria meningitidis, Hemophilus influenzae, or Streptococcus pneumoniae. S. aureus and E. coli are common causes of nosocomial ABM and ABM associated with CNS shunts (S. aureus: ventriculoatrial shunt; E. coli: ventriculoperitoneal shunt), but not community-acquired ABM. (Answer: a, b, c)

a.    Ceftriaxone 2 gm (IV) q12h x 2 weeks
b.    Cefotaxime 3 gm (IV) q6h x 2 weeks
c.    Ceftizoxime 3 gm (IV) q6h x 2 weeks
d.    Chloramphenicol 500 mg (PO) q6h x 2 weeks
e.    Cefuroxime 1.5 gm (IV) q8h

Answer: Ceftriaxone, cefotaxime, or ceftizoxime have good CNS penetration and are effective forms of therapy for community-acquired acute bacterial meningits in the doses described. Oral chloramphenicol is also effective against common ABM pathogens and may be considered as part of IV-to-PO switch therapy or as initial therapy. Although cefuroxime is active against common ABM pathogens, it does not penetrate the CSF well and therefore should not be used for therapy. (Answer: e)

a.    Staphylococcus aureus
b.    Staphylococcus epidermidis
c.    Listeria monocytogenes
d.    Escherichia coli
e.    Klebsiella pneumoniae

Answer: ABM pathogens in elderly or cancer patients include usual pathogens in normal hosts plus Listeria monocytogenes, a gram-positive, aerobic, bacillus. With Listeria meningitis, CSF cultures are positive in 100%, but CSF gram stain is negative in 50%. CSF cell count is < 1000/mm³ in 75% of patients and is predominantly neutrophilic. Listeria may be mistaken for diphtheroids isolated from CSF based on gram stain; such "diphtheroids" should be speciated to rule out Listeria: Listeria are hemolytic on blood agar, diphtheroids are not. Empiric therapy for community-acquired ABM in elderly or cancer patients requires coverage for usual pathogens in normal hosts plus Listeria. (Answer: c)

a.    Ampicillin 2 gm (IV) q4h x 2 weeks
b.    TMP-SMX 5 mg/kg (IV) q6h x 2 weeks
c.    Chloramphenicol 500 mg (IV) q6hx 2 weeks
d.    Ceftriaxone 2 gm (IV) q12h x 2 weeks

Answer: Listeria is the most common ABM pathogen in patients with malignancies, and is a common cause of community-acquired AMB in the elderly. Empiric therapy of ABM in these patients includes coverage of Listeria plus other common pathogens in normal hosts (N. meningitidis, H. influenzae, S. pneumoniae). Specific monotherapy can be administered once the organism is known, including ampicillin, TMP-SMX, or chloramphenicol. Ceftriaxone and other third-generation cephalosporins are not active against Listeria. (Answer: a, b, c)

a.    WBC count of 100-5000 cells/mm³
b.    Opening pressure > 300 mm H₂O
c.    Protein levels > 100 mg/dL
d.    Lactic acid levels > 6 mmol/L
e.    Positive CSF gram stain in > 95%

Answer: CSF analysis is an important diagnostic tool in the approach to the patient with suspected CNS infection. Typical findings in acute bacterial meningitis include a WBC count of 100-5000 cells/mm³ (predominantly PMNs), elevated opening pressure (< 300 mm H₂O in 70%; >300 mm H₂O in 30%), elevated protein levels in 95% (> 200 mg/dL in 50%), elevated lactic acid levels (> 6 mmol/L), and a positive CSF gram stain in 60-90%, depending on the organism. If the WBC count is extremely high (> 20,000 cells/mm³), a CT/MRI should be obtained to exclude brain abscess with rupture into the ventricular system. (Answer: a, c, d)

a.    Always perform lumbar puncture before obtaining a CT scan, even if a suppurative intracranial process is of primary concern
b.    Stiff neck on physical examination is sensitive and specific for the diagnosis
c.    Recurrent fever during the 1st week of H. influenzae meningitis is often due to subdural effusion and requires surgical drainage
d.    On gram stain, S. pneumoniae may be mistaken for H. influenzae, and Listeria may be mistaken for S. pneumoniae

Answer: If ABM is suspected, lumbar puncture should always be performed before obtaining a CT scan, since early antibiotic therapy is critical to prognosis. However, if a mass lesion or suppurative intracranial process is of primary concern, CT/MRI should be obtained before lumbar puncture (but after blood cultures) to avoid herniation. A stiff neck on physical exam has limited diagnostic value in the elderly, since nuchal rigidity may occur without meningitis (e.g., cervical arthritis), and meningitis may occur without nuchal rigidity. Recurrence of fever during the first week of H. influenzae meningitis is commonly due to subdural effusion, which usually resolves spontaneously over several days. On gram stain, S. pneumoniae may be mistaken for H. influenzae, and Listeria may be mistaken for S. pneumoniae. (Answer: d)

a.    Meningeal antibiotic dosing can be reduced as the patient improves
b.    Lumbar puncture should be repeated if the patient is not responding to antibiotics after 48 hours
c.    For S. pneumoniae meningitis, obtain penicillin MICs on all CSF isolates
d.    Dexamethasone 0.15 mg/kg (IV) q6h x 4 days is of proven value in adults to reduce the incidence/severity of neurologic sequelae

Answer: Meningeal antibiotic dosing should not be reduced as the patient improves, since clinical improvement is associated with reduced CSF inflammation and drug penetration. Repeat lumbar puncture is indicated if the patient is not responding to antibiotics after 48 hours; lack of response may be due to therapeutic failure, relapse, or a non-infectious CNS disorder. For S. pneumoniae meningitis, penicillin MICs should be obtained on all CSF isolates. Nearly all penicillin-resistant strains have relatively low MICs (2-5 mcg/mL) and are susceptible to meningeal doses of beta-lactam antibiotics (e.g., ceftriaxone), and all but the most highly penicillin-resistant pneumococci can be effectively treated with meningeal doses of beta-lactams. Highly resistant pneumococcal strains (rare in the CSF) may be treated for 2 weeks with meropenem, cefepime, or linezolid. Dexamethasone 0.15 mg/kg (IV) q6h x 4 days may be given to children with ABM to reduce the incidence/severity of neurologic sequelae. The value of steroids in adult ABM is unclear; if used, dexamethasone should be given 30 minutes before the initial antibiotic dose. (Answer: b, c)

a.    HSV (Herpes simplex virus) meningitis is indistinguishable clinically from other causes of viral meningitis
b.    EBV (Ebstein Barr virus) meningitis is usually associated with clinical/laboratory features of EBV infectious mononucleosis
c.    VZV (Varicella zoster virus) meningitis is infrequently associated with cutaneous zoster
d.    LCM (lymphocytic chorimeningitis) begins as a "flu-like" illness usually in the fall after hamster contact
e.    Enterovirus meningitis is often associated with a maculopapular rash, non-exudative pharyngitis, and diarrhea

Answer: Acute viral meningitis presents with headache, low-grade fever, mild meningismus, and photophobia. Diagnosis is made by specific serological tests and viral culture. HSV-1 causes a variety of CNS infections, including meningitis, meningoencephalitis, or encephalitis (most common). HSV meningitis is indistinguishable clinically from other causes of viral meningitis. EBV meningitis is usually associated with clinical/laboratory features of EBV infectious mononucleosis; suspect the diagnosis in a patient with a positive monospot and unexplained meningoencephalitis. VZV meningitis is typically associated with cutaneous vesicular lesions (H. zoster), and usually does not require additional therapy beyond that given for shingles. LCM meningitis begins as a "flu-like" illness usually in the fall after hamster contact, and may have low CSF glucose. Enterovirus meningitis is often associated with a maculopapular rash, non-exudative pharyngitis, diarrhea, and rarely low CSF glucose. Among these causes of viral meningitis, only HSV has specific therapy (acyclovir, valacyclovir, or famciclovir). Without neurological deficits, full recovery is the rule. (Answer: all are true)

a.    Most patients present with fevers, headache, nausea and cranial nerve abnormalities, spanning over weeks
b.    Evidence of M. tuberculosis infection is often present elsewhere in the body
c.    CSF findings consist of lymphocytosis, low glucose levels, and positive acid-fast bacilli (AFB) smears in most
d.    If multiresistant strains are unlikely, treatment consists of INH 300 mg (PO) q24h plus rifampin 600 mg (PO) q24h x 6-9 months
e.    Full neurological recovery is the rule

Answer: TB (Mycobacterium tuberculosis) meningitis presents with subacute onset of nonspecific symptoms, including fever, headache, nausea, vomiting. Acute presentation and cranial nerve palsies are uncommon. The diagnosis is made by CSF AFB smear/culture, but smears are positive in < 40% (polymerase chain reaction [PCR] of CSF is sensitive and specific). CSF analysis may be normal, but often shows lymphocytosis, low glucose, increased protein, RBCs, and increased lactic acid. CSF may have PMN predominance early, before developing typical lymphocytic predominance. Eosinophils in CSF is not a feature of TB, and should suggest another diagnosis. Look for TB elsewhere, as chest x-ray may show active or prior disease in 50%, and sputum may be positive in 10-20%. Treatment consist of INH 300 mg (PO) q24h plus rifampin 600 mg (PO) q24h x 6-9 months. If a multiresistant strain is likely, ethambutol 15 mg/kg (PO) q24h and pyrizinamide 25 mg/kg (PO) q24h should be added for 6-9 months. TB meningitis is associated with mortality in 10% and persistent neurological deficits in one-third. Proteinaceous TB exudates may obstruct the ventricles and cause hydrocephalus, which is diagnosed by CT/MRI and may require shunting. (Answer: b, d)

a.    Mental status changes, cranial nerve abnormalities and nuchal rigidity are more common in cryptococcal meningitis than TB meningitis
b.    The majority of patients are abnormal hosts (e.g., AIDS, chronic steroid therapy, lymphoreticular malignancies)
c.    India ink smears of CSF are useful for initial infection, but should not be relied on to diagnose recurrent episodes
d.    Treatment consists of amphotericin B plus 5-FC x 6 weeks, followed by fluconazole x 10 weeks

Answer: Cryptococcal meningitis usually presents with the insidious onset (over weeks-to-months) of nonspecific symptoms, most commonly headache, at times with intervening asymptomatic periods. Acute manifestations are more common in AIDS, chronic steroid therapy, or lymphoreticular malignancies. Mental status changes, cranial nerve abnormalities and nuchal rigidity are less common in cryptococcal meningitis than TB meningitis. Fifty-80% of patients with cryptococcal meningitis are abnormal hosts. C. neoformans is the most common cause of fungal meningitis, and the only encapsulated yeast in the CSF to cause meningitis. Diagnosis is made by CSF India ink cryptococcal latex antigen/culture. Patients with cryptococcal meningitis should be tested for HIV and other underlying immunosuppressive diseases. India ink smears of CSF are useful for initial infection, but should not be relied on to diagnose recurrent episodes, since smears may be positive despite negative CSF cultures (dead cryptococci may remain in CSF for years). Diagnosis of recurrences rests on CSF culture. Treatment consists of amphotericin B plus 5-FC x 6 weeks, followed by fluconazole x 10 weeks (until CSF is sterile or initial CSF latex antigen titer is zero or remains near zero on serial lumbar punctures). Amphotericin B lipid formulations may be used if amphotericin B cannot be tolerated. HIV patients require life-long suppressive therapy with fluconazole 200 mg (PO) q24h. Poor prognostic factors include no CSF pleocytosis, many organisms in CSF, or altered consciousness on admission. (Answer: a)

MENINGITIS PITFALLS

PITFALL: TRANSITION FROM IV CEFTRIAXONE TO ORAL 2^nd OR 3^rd GENERATION CEPHALOSPORINS FOR ACUTE BACTERIAL MENINGITIS IN NORMAL HOSTS

ABM in normal hosts is caused by Neisseria meningitidis, Hemophilus influenzae, or Streptococcus pneumoniae, and is usually fatal without therapy. Ceftriaxone 2 gm (IV) q12h is the preferred treatment for ABM, given for a full two-week IV course. Some patients may be started on IV ceftriaxone then switched to oral antibiotics to complete 2 weeks of total therapy. However, transition from IV ceftriaxone to a PO cephalosporin should be avoided, due to the limited ability of oral 2^nd or 3^rd generation cephalosporins to penetrate the blood brain barrier. On the other hand, oral chloramphenicol has excellent (90%) penetration into the CSF, and can be used to treat ABM at a dose of 500 mg (PO) q6h.

PITFALL: DECREASING THE DAILY DOSE OF PENICILLIN IN PNEUMOCOCCAL MENINGITIS AS THE PATIENT IMPROVES CLINICALLY

CSF antibiotic penetration depends on blood brain barrier permeability (degree of meningeal inflammation), which quickly abates with therapy. With penicillin, CSF penetration varies significantly with the degree of meningeal inflammation (CSF penetration is 5% with inflamed meninges and < 1% with noninflamed meninges). To ensure therapeutic penicillin concentrations in the CSF for duration of therapy, meningeal doses of penicillin (4 mu IV q4h) should be maintained and not decreased.

PITFALL: USE OF IV VANCOMYCIN FOR STAPHYLOCOCCAL MENINGITIS

Staphylococcus aureus/epidermidis are very sensitive IV vancomycin, which is commonly used to treat a variety of staphylococcal infections. However, IV vancomycin penetrates the blood brain barrier poorly—CSF penetration in inflamed meninges is only 20%—and should not be used as sole therapy for staphylococcal meningitis. For methicillin-sensitive S. aureus/epidermidis (MSSA/MSSE), useful agents include cefotaxime, ceftizoxime, cefepime, or meropenem. For methicillin-resistant S. aureus/epidermidis (MRSA/MRSE), useful agents include linezolid (IV or PO) or minocycline (PO). If vancomycin is used, it should be administered both IV and intrathecal (IT) to ensure therapeutic concentrations into the CSF. The IT dose of vancomycin is 20 mg, delivered in preservative-free NaCl.