Because of recurrent colonization by Klebsiella pneumoniae strains producing type SHV-4 extended-spectrum beta-lactamases (ESBLs), a case-control study was conducted in an intensive care unit to investigate the risk of acquisition, with special reference to antibiotic therapy and resuscitation procedures. Fifty-one patients colonized or infected by ESBL-producing K. pneumoniae (cases) were matched with 51 noncolonized patients (controls). Duration of intubation was significantly longer for cases than for controls, while duration of beta-lactamase inhibitor therapy was significantly shorter. By means of multivariate analysis, intubation was the only risk factor identified (odds ratio [OR] = 1.19), while beta-lactamase inhibitor therapy was shown to be a protective factor (OR = 0.849). During outbreaks of SHV-4 type ESBL-producing K. pneumoniae in intensive care units, preferential use of beta-lactamase inhibitors may help control the emergence and spread of these pathogens even if essential hand washing and isolation procedures are adhered to.