Background.Organisms of theEnterobacterspp.,Serratia marcescens,Citrobacter freundii, indole-positiveProteusspp.,Providenciaspp. andMorganella morganii(ESCaPPM) group are a common cause of hospital-acquired bacteremia and share the potential to develop beta-lactam resistance during therapy. The emergence of such resistance may have adverse consequences, but the frequency with which this occurs has not been studied in children. It has been suggested that such organisms should be treated with combination antimicrobials or carbapenems, but the optimal regimen is uncertain.Aim.To determine the frequency with which beta-lactam resistance develops during ESCaPPM sepsis in children and the optimal treatment of such sepsis.Methods.A review of the case notes and microbiologic records of all cases of ESCaPPM bacteremia and meningitis managed at a tertiary children’s hospital during a 6-year period.Results.Fifty-eight cases were identified, and in three (5%) cases beta-lactam resistance emerged during treatment, with adverse clinical consequences in two cases. Clinical and microbiologic outcome was similar in those treated with carbapenems and in those treated with a beta-lactam and aminoglycoside combination. Cefotaxime resistance was found in 57, 30, 24 and 7% of children who had received carbapenems, cephalosporins, penicillins or no/other antimicrobials in the month before ESCaPPM sepsis, respectively.Conclusions.The emergence of beta-lactam resistance during treatment of ESCaPPM sepsis is uncommon in our hospital but can have adverse consequences. Where isolates are reported as susceptible to both classes of drugs, an extended spectrum penicillin in combination with an aminoglycoside may be preferable first line treatment of ESCaPPM sepsis to a carbapenem or quinolone.