Bum Sik Chin, et al. M 1 2 3 4 5 6 7 M M 8 9 10 11 12 M 800 - 250 - 200 - 100 - 50 - 800 - 500 - 400 - 250 - 200 - 100 - 50 - A B Fig. 1. Pulsed field gel clectrophoresis (PFGE) analysis of metallo-β- lactamase (MBL)-producing Pseudomonas aeruginosa (A) and Acineto- bacter baumannii (B). Two isolates of Pseudomonas aeruginosa (case no. 1 and no. 2) revealed identical patterns. One of them was an inpatient and the other an outpatient of the same center. The numbers on top of each fig- ure refer to the case numbers described in Table 1. Lane M, molecular weight marker (kb). (56.6% vs. 25%, p = 0.034) were more frequent in the INMNP group. Exposure to antibiotics was also more fre- quent in the INMNP group (76.2% vs. 41.7%, p = 0.015). In the analysis of individual antibiotics, exposure to piper- acillin/tazobactam was significantly more frequent in the INMNP group. Therefore, it was not possible to identify significant risk factor related with MP acquisition among imipenem nonsusceptible isolate acquired patients. Twenty- eight-day and in-hospital case-fatalities after imipenem nonsusceptible isolates acquisition revealed no difference between MPs and INMNPs. With regard to the susceptibilities to the six antibiotics which were frequently used for treatment of PA and AB other than carbapenem (Table 3), the proportions of suscep- tible isolates were higher in the MP group for more than half of the analyzed drugs, and those of piperacillin/tazo- bactam and fluoroquinolones showed statistically signifi- cant differences. Regarding to ceftazidime, only one strain (8.3%) was susceptible among MPs, and this proportion was significantly lower than that of INMNPs (61.7%), which is comparable with previous report.12 However, the aztreonam susceptibility which is known to be uniquely spared among β-lactams against MBL was preserved in only 2 isolates (16.7%) among MPs, and it was not more frequent than that of INMNPs (23.2%). As mentioned above, the clinical data concerning risk factors and treatment outcomes of infections caused by MBL-producing strains are sparse. Analysis of the antimi- crobial chemotherapy administrated before isolation of MPs often revealed that many patients had not been admin- istered with carbapenems, but fluoroquinolones3,13 and β-lactam antibiotics.3,14,15 Other reports suggested carbapen- em use, ICU stay > 20 days,15 underlying neurologic disor- der, urinary tract infection, renal failure,3 and neutropenia14 as contributing factors. However, all of the above men- tioned studies compared an MP group with an MNP group irrespective of the susceptibility to carbapenems, which are now considered as a key drug for the treatment of gram- negative bacilli due to the apparently high barrier to resis- tance acquisition. Therefore, we chose to compare an MP group with an INMNP group rather than with a mere MNP group that includes carbapenem susceptible isolates. Al- though we failed to identify any significant risk factor, this result might be related to the limited number of MPs in our study population. Further investigation is required to ex- plain this aspect. We could not investigate the MP acquisition-related mor- tality because our cases included not only clinical infec- tions, but also colonization. Some authors2,4,5 have reported higher mortality in an MP group. However, they compared the group with MNPs irrespective of carbapenem sensitivi- ty. Although Laupland, et al.16 observed higher mortality in MBL-producing PA infected patients than in the MBL-non- producing carbapenem resistant group, more data are re- quired to ascertain the impact of MBL acquisiton on mor- tality. In a recent study, for example, carbapenem resistance, advanced age, and severity of underlying disease were sug- gested as independent risk factors for mortality, but not VIM-1 type MBL production among Klebsiella pneumoni- ae bloodstream infection patients.17 As regards to the susceptibility of antibiotics other than imipenem, aztreonam is generally an exception, while MBL production results in high-level resistance to most β-lactam antibiotics. However, equivalent resistance profiles for az- treonam have been observed between the MP group and the MNP group in previous reports.3,18,19 Our study also revealed higher percentage of resistance to aztreonam in the MP group. Resistance to aztreonam in MPs might be explained by extended spectrum β-lactamases (ESBL),20,21 AmpC β-lactamases,22-24 or other non-enzymatic mechanisms23 as described before. Therefore, aztreonam may not be an ex- ceptionally useful β-lactam antibiotic for the treatment of MPs in current clinical settings. The portion of strains showing susceptibility for piper- 354 Yonsei Med J http://www.eymj.org Volume 52 Number 2 March 2011