From November 1991 through April 1992, 8 infants developed systemic infections due to antibiotic multiple resistant Klebsiellaa (MRK). All were premature and 6 of the 8 weighed less than 1100 g; 7 of the 8 had received previous antibiotic therapy. Five infections occurred during the first week of life. MRK were isolated from blood (8 cases), tracheal secretions (TS-6), stool (3), and CSF (1). All Klebsiella blood isolates were resistant to ampicillin, mezlocillin, and cefotaxime, 7 of 8 to ceftazidime and amikacin, and 4 of 7 to aztreonam; all isolates were sensitive to quinolones and imipenem. Four infants died. In all 4 of the isolates, they were sensitive only to quinolones and imipenem, and the empiric therapy used for suspected sepsis proved to be inappropriate. The outbreak was terminated by temporary closure of NICU in May 1992. Strict hand washing practices were reemphasized, and the previous empiric antibiotic protocol used for suspected sepsis (mezlocillin plus amikacin, and lately ceftazidime plus amikacin) was changed to imipenem and amikacin in the risk population. At closure, 5 additional infants had MRK in stools and/or tracheal suction specimens. Development of MRK organisms should dictate a rational use of empiric antibiotics for neonatal infections in NICU.