Nosocomial Multiply Resistant Klebsiella pneumoniae : Epidemiology of an Outbreak of Apparent Index Case Origin

Abstract

A nosocomial epidemic of multiply resistant (MR) Klebsiella pneumoniae characterized by resistance to gentamicin, tobramycin, kanamycin, cephalothin, chloramphenicol, and ampicillin occurred in a Veterans Administration hospital from 1975 to 1977. A total of 66 infected or colonized patients were observed in a 2-year period; there were 43 urinary tract infections, 13 wound or soft tissue infections, 8 pneumonias, and 6 patients with only asymptomatic stool colonization. Four patients had both pneumonia and a urinary tract infection. There were five secondary bacteremias. The majority of MR K. pneumoniae strains were type 30, but types 17, 21, and 23 and nontypable organisms were also recovered. Other gram-negative bacilli with the same antibiotic resistance pattern were isolated from 14 patients. Seven MR K. pneumoniae and three resistant Escherichia coli isolates were shown to transfer resistance to E. coli K-12. MR K. pneumoniae-infected patients were seriously ill, had long hospitalization times (mean, 67 days), and were in close geographic proximity to other cases. Compared with controls, cases more frequently had prior antibiotic treatment and urinary catheters, but not respiratory instrumentation, nasogastric tubes, or antacid treatment. The apparent source of the outbreak was traced to an index case who entered the hospital with an MR K. pneumoniae urinary tract infection. Asymptomatic gastrointestinal carriage without infection elsewhere was infrequent (1.6% of cultured patients), but 78% of patients with MR K. pneumoniae infections at other sites also had the organism in their stools. Hospital antibiotic usage was unchanged before and during the outbreak. The identification of an index case and relative lack of asymptomatic stool carriers are unique features of this plasmid-mediated MR K. pneumoniae epidemic. Although this MR K. pneumoniae outbreak appeared to be controlled by the use of isolation techniques, a simultaneous increase in gentamicin resistance among other gram-negative organisms was observed.Klebsiella pneumoniae is the most common cause of nosocomial respiratory tract infections and the second most frequent cause of gramnegative bacteremias and urinary tract infections (4, 10). Certain aspects of the epidemiology of these infections seem clear. Intestinal colonization often precedes clinical evidence of infection, and bacteria in intestinal tracts of patients may serve as an important reservoir for Klebsiella within a hospital (18). How outbreaks due to multiple-drug-resistant (MR) Klebsiella originate is not clear. Increased use of broad-spectrum antibiotics was an associated factor in several instances, but a cause-and-effect relationship was not well established (6,12). In other outbreaks, no changes in selective antibiotic pressures were observed, and the source of the epidemic strain was not determined.During the summer of 1975 the hospital epidemiologist at the 800-bed Minneapolis Veterans Administration Hospital first noted gentamicin resistance among Klebsiella isolates from patie...

Frequency of aminoglycoside 6'-N-acetyltransferase among Serratia species during increased use of amikacin in the hospital

“…Widespread resistance of gram-negative bacilli (GNB) to the aminoglycosides first became apparent at the Minneapolis Veterans Administration Medical Center (MVAMC), a 700-bed acute-care medical-surgical hospital, in the mid1970s (5). Much like the MVAMC experience, increased resistance among GNB at other institutions has been reported to be associated with outbreaks of infection (3,5,7,14).…”

Hospital distribution, persistence, and reintroduction of related gentamicin R plasmids

“…It is unclear whether the continued presence of index-related plasmids at the hospital is due to their ongoing maintenance at the MVAMC since their introduction in 1975 (5,13,14) or to repeated reintroduction of index-related plasmids during the study period. These possibilities are not mutually exclusive.…”

“…Epidemiological studies of gentamicin resistance plasmids have proven that individual plasmids can be responsible for large nosocomial outbreaks of resistant organisms (1-3, 7, 9, 11, 13, 14, 16, 17). A single index plasmid species was responsible for an epidemic of gentamicin-resistant enteric gram-negative bacilli between 1975 and 1976 at the Minneapolis Veterans Administration Medical Center (MVAMC) (5,13,14). The index plasmid first isolated during the 1975 to 1976 outbreak had a mass of about 60 megadaltons (13,14) and encoded resistance to ampicillin, cephalothin, chloramphenicol (most strains), sulfathiazole, kanamycin, neomycin, and tobramycin in addition to gentamicin (5).…”

“…A single index plasmid species was responsible for an epidemic of gentamicin-resistant enteric gram-negative bacilli between 1975 and 1976 at the Minneapolis Veterans Administration Medical Center (MVAMC) (5,13,14). The index plasmid first isolated during the 1975 to 1976 outbreak had a mass of about 60 megadaltons (13,14) and encoded resistance to ampicillin, cephalothin, chloramphenicol (most strains), sulfathiazole, kanamycin, neomycin, and tobramycin in addition to gentamicin (5). Since the initial reports, we have shown that plasmids very similar to the index plasmid that was responsible for the 1975 to 1976 outbreak were present at the MVAMC as late as 1983 and that the population of R plasmids related to the index was stably polymorphic with respect to several DNA rearrangements (8).…”

Evaluation of a Commercial Microdilution System for Quantitative Susceptibility Testing of Aminoglycosides Against Multidrug-Resistant, Gram-Negative Bacilli

“…The MMS method is simple to perform and has been shown to be reproducible and comparable to the International Collaborative Study Group macrodilution broth technique (2). We have compared the MMS method with the agar dilution method and with disk diffusion susceptibility on 168 isolates of gram-negative bacteria isolated from patients in an institution with numerous multidrug-resistant bacteria (7). The system performed well in comparison to standard methods when susceptibility testing of aminoglycosides was evaluated.…”