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Antimicrobial resistance in carbapenem non-susceptible Acinetobacter baumannii (CNSAb) is a major public health concern globally. This study determined the antibiotic resistance and molecular epidemiology of CNSAb isolates from a referral burn center in Tehran, Iran. Sixty-nine CNSAb isolates were tested for susceptibility to antimicrobial agents using the E test methodology. Multiple locus variable number tandem repeat analysis (MLVA), Multilocus sequence typing (MLST) and multiplex PCR were performed. PCR assays tested for ambler classes A, B, and D β-lactamases. Detection of ISAba1, characterization of integrons, and biofilm formation were investigated. Fifty-three (77%) isolates revealed XDR phenotypes. High prevalence of blaOXA-23-like (88%) and blaPER-1 (54%) were detected. ISAba1 was detected upstream of blaADC, blaOXA-23-like and blaOXA51-like genes in, 97, 42, and 26% of isolates, respectively. Thirty-one (45%) isolates were assigned to international clone (IC) variants. MLVA identified 56 distinct types with six clusters and 53 singleton genotypes. Forty previously known MLST sequence types forming 5 clonal complexes were identified. The Class 1 integron (class 1 integrons) gene was identified in 84% of the isolates. The most prevalent (33%) cassette combination was aacA4-catB8-aadA1. The IC variants were predominant in the A. baumannii lineage with the ability to form strong biofilms. The XDR-CNSAb from burned patients in Iran is resistant to various antimicrobials, including tigecycline. This study shows wide genetic diversity in CNSAb. Integrating the new Iranian A. baumannii IC variants into the epidemiologic clonal and susceptibility profile databases can help effective global control measures against the XDR-CNSAb pandemic.

Emerging antimicrobial resistance in burn wound bacterial pathogens is a serious therapeutic challenge for clinicians. In the present study, most of the isolates were MDR. This finding indicated an alarming spread of resistant isolates and suggested that infection control strategies should be considered. Resistance to carbapenems is influenced by several factors, not all of which were evaluated in our study; however, the results showed that production of MBLs and overexpression of the mexB gene were the most frequent mechanisms in carbapenem-resistant isolates.

Two different mechanisms of resistance to colistin in Acinetobacter baumannii have been described. The first involves the total loss of lipopolysaccharide (LPS) due to mutations in the lpxACD operon, which is involved in the lipid A biosynthesis pathway. The second entails the addition of ethanolamine to the lipid A of the LPS resulting from mutations in the PmrAB two-component system. To evaluate the impact of colistin resistance-associated mutations on antimicrobial resistance and virulence properties, four pairs of clinical and laboratory-evolved colistin-susceptible/colistin-resistant (ColS/ColR) A. baumannii isolates were used. Antimicrobial susceptibility, surface motility, in vitro and in vivo biofilm-forming capacity, in vitro and in vivo expression levels of biofilm-associated genes, and in vitro growth rate were analyzed in these strains. Growth rate, in vitro and in vivo biofilm formation ability, as well as expression levels of biofilm-associated gene were reduced in ColR LPS-deficient isolate (the lpxD mutant) when compared with its ColS partner, whereas there were not such differences between LPS-modified isolates (the pmrB mutants) and their parental isolates. Mutation in lpxD was accompanied by a greater reduction in minimum inhibitory concentrations of azithromycin, vancomycin, and rifampin than mutation in pmrB. Besides, loss of LPS was associated with a significant reduction in surface motility without any change in expression of type IV pili. Collectively, colistin resistance through loss of LPS causes a more considerable cost in biological features such as growth rate, motility, and biofilm formation capacity relative to LPS modification. Therefore, ColR LPS-modified strains are more likely to spread and transmit from one patient to another in hospital settings, which results in more complex treatment and control.

BackgroundThe prevalence of pulmonary disease caused by nontuberculous mycobacteria (NTM) is reportedly on the rise in the world. Some of the species are resistant to various antibiotics; hence, limited treatment options are available. The aims of this study were to investigate the prevalence of NTM and to determine the effect of d-cycloserine against Mycobacterium fortuitum and Mycobacterium abscessus isolated from clinical specimens to find out the synergistic effect of d-cycloserine and clarithromycin.MethodsA total of 95 nonduplicate pulmonary isolates of NTM were collected from three major Regional Tuberculosis (TB) Centers. NTM isolates were identified by conventional tests and PCR sequence analysis of the rpoB gene. PCR sequencing of erm-41 was performed for detecting the inducible resistance to macrolides. In vitro susceptibilities and activities of d-cycloserine-clarithromycin combinations were accessed using the broth microdilution method.ResultsAmong 714-positive acid-fast bacilli from TB-suspected cases, 95 isolates were identified as NTM (13.3%). The prevalence of identified isolates was as follows: M. fortuitum 46 (48.4%), Mycobacterium simiae 16 (16.8%), Mycobacterium kansasii 15 (15.7%), M. abscessus 7 (7.3%), Mycobacterium thermoresistibile 4 (4.2%), Mycobacterium elephantis 3 (3.2%), Mycobacterium porcinum 2 (2.1%), and Mycobacterium chimaera 2 (2.1%). In addition, rpoB sequence analysis could identify all NTM isolates. The effect of d-cycloserine was better than that of clarithromycin. The synergistic effect of d-cycloserine with clarithromycin was observed for six (100%) and five (71.5%) strains of M. fortuitum and M. abscessus, respectively.ConclusionIn the present study, we demonstrated a wide range of NTM in processed samples from different provinces of Iran. Our observations indicated that d-cycloserine was very active against M. abscessus and M. fortuitum; hence, d-cycloserine, either alone or in combination with clarithromycin, may be promising for the treatment of M. abscessus- and M. fortuitum-associated diseases.