An antibiotic policy to prevent emergence of resistant bacilli

Lancet. 2000 Mar 18;355(9208):973-8. doi: 10.1016/s0140-6736(00)90015-1.


Background: Fear of infection in neonatal intensive care units (NICUs) often leads to early use of empiric broad-spectrum antibiotics, a strategy that selects for resistant bacteria. We investigated whether the emergence of resistant strains could be halted by modifying the empiric antibiotic regimens to remove the selective pressure that favours resistant bacteria.

Methods: Two identical NICUs were assigned to different empiric antibiotic regimens. On unit A, penicillin G and tobramycin were used for early-onset septicaemia, flucloxacillin and tobramycin were used for late-onset septicaemia, and no broad-spectrum beta-lactam antibiotics, such as amoxicillin and cefotaxime were used. In unit B, intravenous amoxicillin with cefotaxime was the empiric therapy. After 6 months of the study the units exchanged regimens. Rectal and respiratory cultures were taken on a weekly basis.

Findings: There were 436 admissions, divided equally between the two regimens (218 in each). Three neonates treated with the penicillin-tobramycin regimen became colonised with bacilli resistant to the empirical therapy used versus 41 neonates on the amoxicillin-cefotaxime regimen (p<.0001). The relative risk for colonisation with strains resistant to the empirical therapy per 1000 patient days at risk was 18 times higher for the amoxicillin-cefotaxime regimen compared with the penicillin-tobramycin regimen (95% CI 5.6-58.0). Enterobacter cloacae was the predominant bacillus in neonates on the amoxicillin-cefotaxime regimen, whereas Escherichia coli predominated in neonates on the penicillin-tobramycin regimen. These colonisation patterns were also seen when the units exchanged regimens.

Interpretation: Policies regarding the empiric use of antibiotics do matter in the control of antimicrobial resistance. A regimen avoiding amoxicillin and cefotaxime restricts the resistance problem.

MeSH terms

  • Amoxicillin / pharmacology
  • Amoxicillin / therapeutic use*
  • Cefotaxime / pharmacology
  • Cefotaxime / therapeutic use*
  • Cephalosporins / pharmacology
  • Cephalosporins / therapeutic use*
  • Cross-Sectional Studies
  • Drug Resistance, Microbial
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacterial Infections / drug therapy*
  • Humans
  • Infant, Newborn
  • Intensive Care Units, Neonatal* / organization & administration
  • Organizational Policy
  • Penicillins / pharmacology
  • Penicillins / therapeutic use*
  • Prospective Studies
  • Sepsis / drug therapy*


  • Cephalosporins
  • Penicillins
  • Amoxicillin
  • Cefotaxime