Penicillin hypersensitivity regimens for the empirical treatment of meningitis in adults and children 2 months or older

The following empirical regimens are intended for the treatment of meningitis in adults and children 2 months or older in whom the pathogen has not been identified, or susceptibility results are not available. These regimens are for patients who have had a hypersensitivity reaction to a penicillin. In patients with risk factors for Listeria monocytogenes or Streptococcus pneumoniae, add on therapy is required – regimens are included below.

For the empirical treatment of meningitis in adults and children 2 months or older who have had a nonsevere (immediate or delayed) hypersensitivity reaction to a penicillin, use:

1ceftriaxone 2 g (child: 50 mg/kg up to 2 g) intravenously, 12-hourly¹ ceftriaxone ceftriaxone ceftriaxone

1cefotaxime 2 g (child: 50 mg/kg up to 2 g) intravenously, 6-hourly. For dosage adjustment in adults with kidney impairment, see cefotaxime dosage adjustment cefotaxime cefotaxime cefotaxime

PLUS with either of the above regimens

dexamethasone 10 mg (child: 0.15 mg/kg up to 10 mg) intravenously, preferably starting before the first dose of antibiotic, then 6-hourly for 4 days² ³. dexamethasone dexamethasone dexamethasone

For patients who have had a severe immediate⁴ hypersensitivity reaction to a penicillin, ceftriaxone or cefotaxime can be considered if a beta-lactam antibiotic is strongly preferred (for considerations, see Severe immediate hypersensitivity: Implications of cross-reactivity between penicillins and cephalosporins).

For patients who have had a severe immediate⁴ hypersensitivity reaction to a penicillin in whom ceftriaxone or cefotaxime is not used, or for patients who have had a severe delayed⁵ hypersensitivity reaction to a penicillin, use:

moxifloxacin 400 mg (child: 10 mg/kg up to 400 mg) intravenously, daily⁶ ⁷. For dosage adjustment in adults with kidney impairment, see moxifloxacin dosage adjustment moxifloxacin moxifloxacin moxifloxacin

PLUS

dexamethasone 10 mg (child: 0.15 mg/kg up to 10 mg) intravenously, preferably starting before the first dose of antibiotic, then 6-hourly for 4 days² ³.

Listeria monocytogenes infection should be treated empirically in patients at risk of infection, including patients who:

are older than 50 years
have immune compromise
are pregnant
have a history of hazardous alcohol consumption.

Benzylpenicillin is the preferred drug for Listeria infection because L. monocytogenes is intrinsically resistant to cephalosporins. However, benzylpenicillin may not be appropriate for patients who have penicillin hypersensitivity. For patients who report penicillin hypersensitivity, carefully assess the nature and severity of the reaction (see Clinical history for initial assessment of patients reporting penicillin hypersensitivity) and consider whether use of benzylpenicillin is precluded.

If benzylpenicillin is used, see Standard regimens for the empirical treatment of meningitis in adults and children 2 months or older.

If benzylpenicillin is not used, add trimethoprim+sulfamethoxazole to either of the above regimens:

trimethoprim+sulfamethoxazole (adult and child 1 month or older) 5+25 mg/kg up to 480+2400 mg intravenously, 8-hourly. For dosage adjustment in adults with kidney impairment, see trimethoprim+sulfamethoxazole dosage adjustment. trimethoprim + sulfamethoxazole trimethoprim+sulfamethoxazole trimethoprim+sulfamethoxazole

Vancomycin is added to the above regimens to ensure that empirical therapy is adequate for S. pneumoniae isolates that have reduced susceptibility or resistance to penicillin or cephalosporins. Add vancomycin if:

gram-positive diplococci are seen on Gram stain
pneumococcal antigen assay of cerebrospinal fluid (CSF) is positive
the patient has known or suspected otitis media or sinusitis
the patient has been recently treated with a beta-lactam antibiotic.

Also consider adding vancomycin if:

gram-positive cocci resembling staphylococci are seen on Gram stain
CSF tests are not possible because lumbar puncture is contraindicated.

Add:

vancomycin intravenously vancomycin vancomycin vancomycin

adult: 25 mg/kg (actual body weight) rounded up to nearest 125 mg, up to 3 g, as a loading dose. See Calculated vancomycin loading dosage in critically ill adults for calculated weight-based loading doses. Subsequent doses are dependent on weight and kidney function; see Intermittent vancomycin dosing for critically ill adults

child: for initial dosing, see Intermittent vancomycin dosing for young infants and children.

If vancomycin is used, administer it after ceftriaxone, cefotaxime or moxifloxacin due to the long infusion time required.

¹ In children, a single daily dose of ceftriaxone (100 mg/kg up to 4 g intravenously, daily) is used in some centres. A single daily dose of ceftriaxone may also be used when patients complete their course of treatment at home in an ambulatory antimicrobial therapy program.Return

² If dexamethasone is not available, hydrocortisone (200 mg [child: 4 mg/kg up to 200 mg] intravenously) may be used for the initial dose.Return

³ If the pathogen is known to be Neisseria meningitidis or Streptococcus agalactiae (group B streptococcus), steroids should not be given because steroid therapy is of no benefit.Return

⁴ Severe immediate hypersensitivity reactions include anaphylaxis, compromised airway, airway angioedema, hypotension and collapse.Return

⁵ Severe delayed hypersensitivity reactions include cutaneous adverse drug reactions (eg drug rash with eosinophilia and systemic symptoms [DRESS], Stevens–Johnson syndrome/toxic epidermal necrolysis [SJS/TEN], severe blistering or desquamative rash), and significant internal organ involvement (eg acute interstitial nephritis).Return

⁶ Moxifloxacin is not licensed for use in children on the basis of animal studies that showed an adverse effect on cartilage development with quinolone use; however, clinical trial data suggest that adverse musculoskeletal events are usually mild and short term, similar to those observed in adults. Moxifloxacin can be used in children when it is the drug of choice.Return

⁷ If gram-positive cocci resembling streptococci are seen on Gram stain, vancomycin does not need to be added to moxifloxacin because moxifloxacin provides adequate empiric cover for Streptococcus pneumoniae isolates that have reduced susceptibility or resistance to penicillin or cephalosporins.Return