The production of carbapenem hydrolyzing enzymes as well as producing a polysaccharide matrix in respiratory infections is one of the most significant mechanisms for resistance to carbapenems in P. aeruginosa strains (14, 15). However, not only the sputum isolates of this study were resistant to all antibiotics tested, but also 11 (42.3%) of them were detected as MDR. On the other hand, our clinical isolates had a relatively low resistance rate (< 40%) against all antibiotics tested, except gentamicin, as well as other Iranian studies (3, 16). However, the studies conducted by Radan et al. in 2016, and Mirsalehian et al. in 2017, reported the higher antibiotic resistance rate (5, 13), may be due to the type of samples, as all isolates collected from burn sections. Since patients with burns may be exposed to broad-spectrum antibiotics pressure, high antibiotic resistance rate observes in these wards (13). In another study conducted in Hamedan, as in our study, the lowest antibiotic resistance of the P. aeruginosa clinical isolates was reported against piperacillin-tazobactam (17). It seems that this antibiotic is still one of the effective drugs against this bacterium in Iran.
In the present study, the resistance rate against imipenem (28%) was similar to other studies in Iran (6, 18). On the other hand, the resistance towards imipenem and doripenem in the present study was less than meropenem. According to our assessment, the use of meropenem for the treatment of infections caused by this bacterium in our investigated hospitals was more than imipenem, while the doripenem is not widely used in the treatment of these infections. In another Iranian study conducted in 2017, the resistance to imipenem (8.4%) and meropenem (9.5%) was higher than that of penicillin (7.4%) (3). Also, in some studies, colistin has reported as an effective drug against multidrug-resistant as well as carbapenem-resistant P. aeruginosa (13), while 26% of our isolates detected as colistin-resistant. However, 8 (20%) MDR isolates in our study were resistant to colistin. The rate of colistin-resistance in clinical isolates of P. aeruginosa in other studies conducted in Iran and Iraq have reported as 11% and 18.2%, respectively (17, 19).
In the present study, out of 43 carbapenem-resistant isolates, 33 (76.74%) isolates were CDT positive consistent with some studies conducted in Iran and other countries (12, 20). According to the recent studies, we are witnessing an increasing prevalence of MBLs in clinical isolates of P. aeruginosa. The rate of MBLs in Kerman was negative in 2008 (21), while in 2015, it was 48% in Isfahan (7), however, in another study conducted in India, 37.5% of the P. aeruginosa clinical isolates have reported as MBL-producer (22). IMP is one of the most important Metallo-beta-lactamases causing resistance to beta-lactams and carbapenems (23), whereas in this study, all three isolates carrying the IMP gene were resistant to the carbapenems. In an Iranian study conducted in 2019, 4.7% of the isolates contained the IMP gene (6), while in another study conducted in India, out of all CDT positive isolates, 3% of them were carrying the IMP gene (20). Studies in Asian, African, and North American countries such as South Korea, India, Egypt, and Canada (9, 20, 24, 25) have reported an IMP gene prevalence of between 2 and 8%, indicating that the prevalence of this gene is low as well as our results.
On the other hand, some studies in Iran and other countries reported no SPM positive P. aeruginosa (7, 8, 26), however, Azimi et al. in 2018 reported a prevalence of 5.6% and 15.6% of the SPM and IMP gene, respectively, while all of their isolates collected from children admitted to the burn ward (27). The absence of the SPM gene and the low prevalence of the IMP gene in this study indicate that other mechanisms such as increased expression of efflux pumps, decreased expression of outer membrane proteins, and production of other carbapenemases may have involved in the development of carbapenem-resistant strains in this region. Considering the importance of carbapenem-resistant, colistin-resistant, and MDR isolates of Pseudomonas aeruginosa, routine antibiotic susceptibility testing and using more modern phenotypic tests such as Modified Hodge test and CarbaNP test are essential for the initial identification of carbapenemase-producing P. aeruginosa.
Limitations
The present study had some limitations. Lack of information about other carbapenemase encoding genes belonging to MBL group and genetic relationship between the resistant strains are not determined.