Is OmpK35 Specific for Ceftazadime Penetration?

In a recent article, Rasheed et al. postulated that OmpK35 in Klebsiella pneumoniae is specific for ceftazadime penetration (2). The conclusion is based on kinetic data from their study and an observation from a previous study by Martínez-Martínez et al. (1).

According to the kinetic data reported by Rasheed et al., the relative hydrolytic efficiency of cefotaxime was approximately 15 times greater than that of ceftazidime; cefotaxime resistance was therefore thought to be higher than that of ceftazidime due to the higher affinity. Unpredictably, the MICs of ceftazidime and cefotaxime for K. pneumoniae K6 were 32 and 8 μg/ml, respectively. Subsequently, the authors found ompK35 was not expressed in K. pneumoniae K6. Rasheed et al. thought that porin loss may help explain why the MIC of ceftazidime is higher that of cefotaxime. The study by Martínez-Martínez et al. was cited in support of this conclusion. My principal objection to this explanation is that Martínez-Martínez et al. never discussed the contribution of ceftazidime resistance due to OmpK35 loss (1). In that study, an OmpK36 gene carrier was cloned back into an OmpK35- and ompK36-deficient strain, and a reduction in the MIC of cefotaxime was observed. Although the MIC of ceftazdime had not changed, SHV-5 production in the deficient strain cannot be excluded. In addition, the MIC of cefotaxime remained at 4 μg/ml for the cloned strain, suggesting that SHV-5 plays an important role in resistance. Rasheed et al. state that SHV-5 is thought to have little effect on the hydrolysis of cefotaxime but is necessary for resistance to ceftazidime. Therefore, conclusions about OmpK35 are premature, since production of the extended-spectrum β-lactamase cannot be excluded. Secondly, for a transconjugant (HB101 TC-K6/1) of an SHV-18 carrier, the MICs of cefotaxime and ceftazidime were 1 and 8 μg/ml, respectively (2). A 16-fold reduction in the MIC of cefotaxime for TC-K6/1 was observed compared to the original K6. On the other hand, a fourfold reduction in the MIC of ceftazidime was detected. If OmpK35 is specific for ceftazidime, the MIC of ceftazidime should be significantly reduced and the MIC of cefotaxime should not be affected much. Further experimental work should be conducted.