Risk factors and clinical responses of pneumonia patients with colistin-resistant Acinetobacter baumannii-calcoaceticus

BACKGROUND Nosocomial infections with carbapenem-resistant Acinetobacter baumanniicalcoaceticus complex(ABC)strains are great problem for intensive care units.ABC strains can develop resistance to all the antibiotics available.Carbapenem resistance is common and colistin resistance is rare in our country.Knowing the risk factors for colistin resistance is important since colistin seems to be the only remaining therapeutic option for the patients with pneumonia due to extensively drug resistant ABC for our country.AIM To investigate the comparison of clinical responses and outcomes between pneumonia patients with colistin-susceptible and-resistant Acinetobacter sp.Strains.METHODS During the study period,108 patients with pneumonia due to colistin-susceptible strains and 16 patients with colistin-resistant strains were included retrospectively.Continuous variables were compared with the Mann-Whitney U test,and categorical variables were compared using Pearson’s chi-square test or Fisher’s Exact chi-square test for two groups.A binary logistic regression model was developed to identify the potential independent factors associated with colistin resistance in patients with colistin-resistant strains.RESULTS High Acute Physiology and Chronic Health Evaluation II scores(OR=1.9,95%CI:1.4-2.7;P<0.001)and prior receipt of teicoplanin(OR=8.1,95%CI:1.0-63.3;P=0.045)were found to be independent risk factors for infection with colistin-resistant Acinetobacter sp.Different combinations of antibiotics including colistin,meropenem,ampicillin/sulbactam,amikacin and trimethoprim/sulfamethoxazole were used for the treatment of patients with colistin-resistant strains.Although the median duration of microbiological cure(P<0.001)was longer in the colistin-resistant group,clinical(P=0.703),laboratory(P=0.277),radiological(P=0.551),microbiological response(P=1.000)and infection related mortality rates(P=0.603)did not differ between the two groups.Among the patients with infections due to colistin-resistant strains,seven were treated with antibiotic combinations that included sulbactam.Clinical(6/7)and microbiological(5/7)response rates were quite high in these patients.CONCLUSION The optimal therapy regimen is unclear for colistin-resistant Acinetobacter sp.infections.Although combinations with sulbactam seems to be more effective in our study patients,data supporting the usefulness of combinations with sulbactam is very limited.     

Evaluation of sulbactam and colistin/sulbactam efficacy against multiple resistant Acinetobacter baumannii blood isolates

PurposeWe aimed to compare the results of the BD Phoenix (TM) M50 ID/AST system and the gold standard broth microdilution method. We also evaluated the potential of a new therapeutic combination (colistin/sulbactam) for colistin resistance among Acinetobacter baumanni strains.MethodsGrowth in blood samples was detected with the BACTEC (BD Becton Dickinson, ABD) continuous monitoring blood culture system. Strains were identified by Phoenix (BD Phoenix? M50, ABD) automated bacterial identification system and antimicrobial susceptibility results were obtained. A total of 92 A. baumannii complex isolates showing resistance to at least three antibiotic classes were included in the study. Colistin susceptibility results (both susceptible and resistant strains) detected by the Phoenix device were confirmed by the reference method, the liquid microdilution method. The concentration index (FIC) was used to determine the efficacy of fractional inhibitor drug combinations, the efficacy of colistin/sulbactam combination against 50 multiresistant A. baumannii complex strains was investigated using the checkerboard method.Results10 (10.9%) of 92 isolates were resistant to colistin and 80 (86.9%) to sulbactam. With the automation system, only 2 of 10 isolates were found resistant to colistin, while 8 isolates were susceptible. For this reason, the very major error rate of the Phoenix M50 automatic system among resistant isolates was determined as 8/10. It was determined that 6 (12%) of the colistin/sulbactam combination had a synergistic effect and 44 (88%) had an additive interaction. No antagonistic interaction was detected with the colistin–sulbactam combination in this study.ConclusionA. baumannii strains should be confirmed by the broth microdilution method, which is the reference method, against the MIC results detected by automated systems. It was concluded that the use of colistin alone should be avoided in the treatment of A. baumannii infections.     

Emergence of colistin resistance in Enterobacter aerogenes from Croatia

A colistin-resistant Enterobacter aerogenes [study code 12264] was isolated from the tracheal aspirate of a 71-year-old male patient in the General Hospital [GH] in Pula, Croatia. The patient was previously treated in University Hospital Centre in Rijeka with colistin in order to eradicate Acinetobacter baumannii isolate, susceptible only to colistin and tigecycline. Genes encoding ESBLs [bla_TEM, bla_SHV, bla_CTX-M, bla_PER-1] were screened by PCR. The strain was shown to possess bla_CTX-M-15 and bla_TEM-1 genes. To asses genes possibly involved in resistance to colistin the chromosomal enconding mgrB gene and the plasmid-mediated mcr-1 and mcr-2 genes were screened as described previously. Mcr-1 and mcr-2 genes were not detected and mgrB gene presented a wild-type sequence. PCR-based Replicon typing method [PBRT] conducted on an E. aerogenes isolate, showed that the strain carried an IncN plasmid. Adaptive mechanisms such as changes of the bacterial cell outer membrane that cause porin decrease or presence of an efflux pump, due to selection pressure exerted by the therapeutic administration of colistin, could be responsible for the development of colistin resistance in our strain, as recently reported in E. aerogenes from France. Due to effective infection control measures, the colistin-resistant strain did not spread to other patients or hospital wards. This is the first report of an ESBL-producing, colistin-resistant E. aerogenes in clinically relevant samples such as endotracheal aspirate and blood culture, showing the presence of this rare resistance profile among Gram-negative bacteria.     

Potentialization of β-lactams with colistin: in case of extended spectrum β-lactamase producing Escherichia coli strains isolated from children with urinary infections

Five strains producing extended-spectrum β-lactamases (ESBL) bacteria, identified as Escherichia coli, were isolated from children with urinary infections hospitalized at Roubaix hospital in the north of France. The DNA genotypes of these non-nosocomial isolates were determined by Random Amplified Polymorphic DNA (RAPD) method. Further, their DNA plasmids content revealed the presence of two distinct plasmids for S1, S2, S3 and one plasmid for S4 and S5. The antibacterial susceptibility of these ESBL bacteria was tested mainly against antibiotics of β-lactams family. The ESBL producing bacteria were resistant to ticarcillin and cefotaxime but the combination of these antibiotics with colistin has dropped the MIC of ticarcillin below its breakpoint (isolates S2, S3 and S4), and has almost reached the breakpoint for cefotaxime (isolate S2). Thus, kill curves analyses carried out with only isolates S1 and S2, strengthened the bactericidal activity of the combinations of colistin-ticarcillin and colistin-cefotaxime against ESBL E. coli. Indeed, reduction of 3 log₁₀ colony count were observed after 24 h of incubation.     

Determination of synergy between sulbactam,meropenem and colistin in carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii isolates and correlation with the molecular mechanism of resistance

Treatment of infections with carbapenem-resistant Gram negative organism is a major challenge especially among intensive care patients. Combinations of sulbactam, meropenem and colistin was studied for its synergistic activity against 100 invasive isolates of carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii-calcoaceticus complex by checkerboard assay and time kill assay (TKA). In addition, presence of carbapenemase production was determined by multiplex PCR. Time kill assay detected more synergy than checkerboard assay. Good bactericidal activity of 70–100% was noted with the combinations tested. Among K. pneumoniae, isolates producing NDM carbapenemase alone showed significantly more synergy than isolates producing OXA-48-like carbapenemases. In treatment of infection with carbapenem-resistant organisms, the site of infection and the type of carbapenemase produced may help to determine the most effective combination of antimicrobials.