Impact of Antimicrobial Resistance on Treatment Regimens for Meningitis

Development of resistance to ^-lactam antibiotics, including penicillins and cephalosporins, has significantly impacted the management of bacterial meningitis. Approximately 17% of U.S. pneumococcal CSF isolates are resistant to penicillin, and

3.5% of CSF isolates are resistant to cephalosporins. The Clinical and Laboratory Standards Institute (CLSI) has set a lower ceftriaxone susceptibility breakpoint for pneumococcal CSF isolates (1 mg/L) than for isolates from non-CNS sites (2 mg/L). Increasing pneumococcal resistance to penicillin G has changed empirical treatment regimens to the combination of a third-generation cephalosporin plus vancomycin. Recognition of relative and high-level resistance to N. meningitidis in the laboratory, as well as in clinical treatment failures, has led to greater use of third-generation ceph-

alosporins for empirical therapy of meningococcal meningitis. Traditionally, ampi-cillin was the cornerstone of treatment for H. influenzae meningitis. Now, treatment of suspected or proven ^-lactamase-mediated Hib meningitis requires a third-generation cephalosporin. Increasing rates of methicillin-resistant S. aureus (about one-third of staphylococcal CSF isolates) and coagulase-negative staphylococci require the use of vancomycin for empirical therapy when these pathogens are suspected. 9 As previously mentioned, hospitalized patients, especially those residing in an intensive care unit, are at risk for developing meningitis secondary to gram-negative pathogens. The emergence and continued rise of multidrug resistant strains of gram-negative organisms such as Pseudomonas aeruginosa, Acinetobacter species, AmpC and extended spectrum ^-lactamase (ESBL)-producing strains of Enterobacteraciae have become a recognized threat nationally. Global and local resistance patterns should be taken into account and combined with optimized pharmacodynamic dosing strategies when designing empirical treatment regimens for bacterial meningitis.

Suspicion Of bacterial meningitis11

I Ves

Immunocompromised. history of CMS d sease, new onset seizure, papilledema, altered consciousn&ss, or focal neurologic deficit, or delay in performance ol diagnostic lumbar puncture

Blood cuUures and lumbar puncture STAT

Blood cuUures and lumbar puncture STAT

Empiric antimicrobial! therapy^' + Dexamettia^e'1

CSF findings consistent witft bacterial meningilis


Posiiive CSF Gram stain

Blood cultures STAT

empiric affllrn icrobiai tnerapy^ + Dej(ametna&onec

Negative CT scan ol Ihe head

Perform lumbar puncitire

Posiiive CSF Gram stain



Empine antinnicroDiai therapy*

Targeted antimicrobial Iherapy*'



FIGURE 70-2. Management algorithm for adults with suspected bacterial meningitis. a Management algorithm is similar for infants and children with suspected bacterial meningitis. See Table 70-1 for empirical treatment recommendations. c See text for specific recommendations for use of adjunctive dexamethasone in adults with bacterial meningitis. d See Table 70-3 for pathogen-based definitive treatment recommendations. (Adapted, with permission, from Ref. 14.)

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