In Papua New Guinean (PNG) children with acute bacterial meningitis (ABM), all Haemophilus influenzae isolates were resistant to chloramphenicol. Although Streptococcus pneumoniae isolates had a median chloramphenicol MIC of 3 μg/ml, it was ≥4 μg/ml in 42.8%, and the likelihood of an area under the 24-hour concentration-time curve/MIC ratio of >100 h at a MIC of ≥4 μg/ml was approximately 50%. All isolates were ceftriaxone sensitive. These data support ceftriaxone rather than conventional chloramphenicol for all PNG children with suspected ABM.