Page 925 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

656 PART 5: Infectious Disorders

TABLE 71-5 Recommended Doses of Antibiotics for Intracranial Infections which accounted for approximately 25% to 33% of all isolates in the
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in Adults With Normal Renal Function United States. Chloramphenicol resistance has also been reported in
the United States (<1% of isolates) and Spain (≥50% of isolates). In
Antibiotic Total Daily Dose in Adults (Dosing Interval) addition, a study found chloramphenicol to be bacteriologically and
Amikacin a 15 mg/kg (q8h) clinically inferior to certain β-lactam antibiotics (ampicillin, ceftriax-
one, and cefotaxime) in childhood bacterial meningitis, and most of
Ampicillin 12 g (q4h)
these cases were due to H influenzae type b. From these findings and
Aztreonam 6-8 g (q6-8h) those of other studies, the third-generation cephalosporins (eg, cefo-
Cefepime 6 g (q8h) taxime and ceftriaxone) seem to be at least as effective as ampicillin plus
chloramphenicol for therapy of H influenzae meningitis. Cefuroxime, a
Cefotaxime 8-12 g (q4-6h)
second-generation cephalosporin, has also been evaluated for therapy of
Ceftazidime 6 g (q8h) H influenzae meningitis. A prospective randomized study of ceftriaxone
Ceftriaxone 4 g (q12-24h) versus cefuroxime for the treatment of childhood bacterial meningitis
Ciprofloxacin 800-1200 mg (q8-12h) documented the superiority of ceftriaxone; patients receiving this drug
had milder hearing impairment and more rapid CSF sterilization than
Gentamicin, tobramycin a 5 mg/kg (q8h) did those receiving cefuroxime. We currently recommend a third-
a
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Meropenem 6 g (q8h) generation cephalosporin for empirical therapy when H influenzae is
Metronidazole 30 mg/kg (q6h) considered a likely infecting pathogen. Cefepime has similar in vitro
activity and cure rates for bacterial meningitis caused by H influenzae,
Nafcillin, oxacillin 9-12 g (q4h)
N meningitidis, and S pneumoniae; in a prospective randomized trial
Rifampin 600 mg (q24h) comparing cefepime to cefotaxime for the treatment of bacterial menin-
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Trimethoprim-sulfamethoxazole 10-20 mg/kg (q6-12h) gitis in infants and children, cefepime was found to be safe and thera-
b
peutically equivalent to cefotaxime.
Vancomycin c 30-60 mg/kg (q8-12h)
The treatment of bacterial meningitis in adults that is caused by gram-
a Need to monitor peak and trough serum concentrations. negative enteric bacilli has been revolutionized by the third-generation
b Dosage based on trimethoprim component. cephalosporins, 21,29 with cure rates of 78% to 94%. Ceftazidime or
c Maintain serum trough concentrations of 15-20 µg/mL. cefepime are also active against P aeruginosa meningitis; ceftazidime,
alone or in combination with an aminoglycoside, resulted in cure of 19
of 24 patients with Pseudomonas meningitis in one report. Intrathecal
even when patients are receiving adjunctive dexamethasone as long or intraventricular aminoglycoside therapy should be considered if
as appropriate dosages of vancomycin are administered; in one study there is no response to systemic therapy, although this therapy is now
of 14 patients, administration of intravenous vancomycin (15 mg/kg rarely needed. The fluoroquinolones (eg, ciprofloxacin or pefloxacin)
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loading dose, followed by a continuous infusion of 60 mg/kg per day) have been used in some patients with gram-negative bacillary men-
led to mean CSF concentrations of 7.2 µg/mL. Some investigators ingitis, but at this time they can be considered only for patients with
have recommended the addition of rifampin (if the organism is sus- meningitis due to multidrug-resistant gram-negative bacilli or for
ceptible) to the combination of vancomycin plus the third-generation patients in whom conventional therapy has failed. Given the emergence
cephalosporin for the treatment of meningitis caused by highly resistant of strains of gram-negative bacilli that are resistant to third-generation
pneumococcal strains, 21,29,32 although there are no firm data to support cephalosporins, use of other intravenous agents, with or without intra-
this. Meropenem, a carbapenem antimicrobial agent, yields microbio- ventricular administration, may need to be considered. 13,32 Especially in
logic and clinical outcomes similar to those of cefotaxime or ceftriaxone patients with meningitis caused by multidrug-resistant Acinetobacter
in the treatment of patients with bacterial meningitis. The newer fluo- species, empiric therapy should be meropenem, with or without an
roquinolones (eg, moxifloxacin) have in vitro activity against resistant aminoglycoside administered by the intraventricular or intrathecal
pneumococci and have shown activity in experimental animal models route. Colistin (usually formulated as colistimethate sodium) should be
of resistant pneumococcal meningitis, 21,29,32 but should not be used substituted for meropenem if the organism is found to be resistant to
as first-line therapy in patients with bacterial meningitis, pending carbapenems, and may also need to be administered by the intraven-
results of ongoing clinical trials. Trovafloxacin was shown to be thera- tricular or intrathecal route.
peutically equivalent to ceftriaxone with or without vancomycin for the The third-generation cephalosporins are inactive against meningitis
treatment of pediatric bacterial meningitis, although this agent is no caused by L monocytogenes, an important meningeal pathogen; this is a
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longer used because of concerns of liver toxicity. The combination of major drawback of these agents. Therapy in this situation should consist
moxifloxacin plus either vancomycin or a third-generation cephalospo- of ampicillin or penicillin G; addition of an aminoglycoside should be
rin may emerge as a treatment option for patients with pneumococcal considered in documented infection, at least for the first several days of
meningitis. treatment. 18,19,21,29,32 Alternatively, trimethoprim sulfamethoxazole can
-
Meningococcal strains that are relatively resistant to penicillin have be used. In one retrospective series, the combination of trimethoprim-
also been reported from several areas (in particular Spain); however, sulfamethoxazole plus ampicillin was associated with a lower failure rate
most patients harboring these strains have recovered with standard and fewer neurologic sequelae than the combination of ampicillin plus
penicillin therapy, so their clinical significance is unclear. In addition, in an aminoglycoside, although more data are needed before this combi-
one study in Ontario, there was no association between invasive menin- nation can be recommended. Patients with S aureus meningitis should
gococcal disease in decreased susceptibility to penicillin and mortality, be treated with nafcillin or oxacillin; vancomycin should be reserved
although there was a marked increase in mortality associated with for patients allergic to penicillin and patients with suspected or proven
infection caused by serogroups B and C. In the United States, approxi- disease caused by methicillin-resistant organisms. 21,22,29,32 Linezolid has
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mately 3% of meningococcal strains have shown intermediate suscep- been successfully utilized in some patients with MRSA CNS infections,
tibility to penicillin. 21,29,32 Some authorities would treat meningococcal and the combination of daptomycin plus rifampin was successful in
meningitis with a third-generation cephalosporin (cefotaxime or ceftri- some patients with MRSA meningitis. Infection with S epidermidis, the
axone) pending results of in vitro susceptibility testing. most likely isolate in a patient with a CSF shunt, should be treated with
Treatment of H influenzae type b meningitis has been hampered vancomycin, with rifampin added if the patient fails to improve. 13,29
by the emergence of β-lactamase–producing strains of the organism, Shunt removal is often essential to optimize therapy.

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