Choice of empiric antibiotics in adults with possible community-acquired bacterial meningitis with reported past hypersensitivity reactions to beta-lactam antibiotics

Past beta-lactam reaction	Initial regimen	Comments
Mild cutaneous reactions to a penicillin (eg, mild drug eruptions, with or without pruritus, immediate or delayed), including isolated mild hives to a penicillin without other signs of anaphylaxis, especially if the reaction occurred in childhood and/or >10 years ago.	Ceftriaxone or cefotaxime plus Vancomycin	If Listeria coverage is required (eg, patients >50 years of age and/or immunocompromised hosts), trimethoprim-sulfamethoxazole should be initiated. Immunocompromised patients generally require expanded gram-negative coverage (eg, cefepime or meropenem instead of ceftriaxone or cefotaxime).* If meropenem is used, it provides sufficient coverage for Listeria when used as part of an initial empiric regimen.
Isolated mild hives to a cephalosporin without other signs of anaphylaxis (especially if the reaction occurred in childhood and/or >10 years ago) Or Mild delayed type reactions to cephalosporins.	Meropenem plus Vancomycin	Meropenem provides sufficient coverage for Listeria and Pseudomonas aeruginosa when used as part of an initial empiric regimen.*
Severe immediate allergy (eg, anaphylaxis) to a penicillin and/or cephalosporin Or SJS/TEN, DRESS, or AGEP with any beta-lactam other than aztreonam.	Moxifloxacin^¶ plus Vancomycin	If Listeria coverage is required (eg, patients >50 years of age and/or immunocompromised hosts), trimethoprim-sulfamethoxazole should be initiated. Immunocompromised patients generally require expanded gram-negative coverage.* If expanded gram-negative coverage is required, aztreonam should be added as long as there is no history of serious allergy (eg, anaphylaxis, SJS/TEN, DRESS, AGEP) to aztreonam itself or an immediate or IgE-mediated allergy to ceftazidime.
Other uncommon forms of hypersensitivity	Initial regimen	Comments
Interstitial nephritis^Δ, or drug-induced liver disease^Δ◊, or drug-induced cytopenia^Δ, or serum sickness^Δ	Ceftriaxone or cefotaxime plus Vancomycin	If Listeria coverage is required (eg, patients >50 years of age and/or immunocompromised hosts), trimethoprim-sulfamethoxazole should be initiated. Immunocompromised patients generally require expanded gram-negative coverage (eg, cefepime or meropenem instead of ceftriaxone or cefotaxime).* If meropenem is used, it provides sufficient coverage for Listeria when used as part of an initial empiric regimen.

This table discusses empiric antibiotic selection for the initial regimen in patients with a beta-lactam allergy. Once the organism is identified, therapy should then be tailored to the best available agent. If the most appropriate treatment was not initiated due to a beta-lactam allergy, the patient should be managed in conjunction with a drug allergy specialist to see if the type of past allergy is amenable to rechallenge or desensitization.

IV: intravenous; SJS/TEN: Stevens-Johnson syndrome/toxic epidermal necrolysis; DRESS: drug reaction with eosinophilia and systemic symptoms; AGEP: acute generalized exanthematous pustulosis.
* Refer to the topic that discusses initial selection of antibiotics for treatment of bacterial meningitis for a more detailed discussion of which patients require expanded gram-negative coverage and regimen selection in this setting.
¶ Patients with a severe immediate allergy (eg, anaphylaxis) to a penicillin or cephalosporin can usually tolerate meropenem, because cross-reactivity rates between penicillins or cephalosporins and carbapenems for patients with proven immediate allergy are <1%. However, in such patients, meropenem should be administered using a test dose procedure. Thus, to avoid delays in initiating treatment, it is reasonable to administer moxifloxacin for the initial dose in an emergency room setting, and then transition to meropenem while awaiting the final culture results. Test dose protocols are reviewed in the topic that discusses the use of antibiotics in penicillin-allergic hospitalized patients.
Δ Interstitial nephritis, drug-induced liver disease, drug-induced cytopenias, and serum sickness (as well as serum sickness-like reactions) tend to be drug specific. This type of reaction to a penicillin in the past would not necessitate avoidance of cephalosporins.
◊ Commonly implicated drugs are amoxicillin-clavulanate in North America and flucloxacillin in Europe.

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Choice of empiric antibiotics in adults with possible community-acquired bacterial meningitis with reported past hypersensitivity reactions to beta-lactam antibiotics