Rate Of Colistin Resistance Research Articles

A Systematic Review and Meta-Analysis of Molecular Characteristics on Colistin Resistance of Acinetobacter baumannii.

This study aimed to determine the molecular epidemiology of colistin-resistant A. baumannii in the last ten years and the frequency of gene regions related to pathogenesis, to compare the methods used to detect genes, and to confirm colistin resistance. This meta-analysis study was conducted under Preferred Reporting Items for Systematic Reviews and Meta-Analysis Guidelines. In the meta-analysis, research articles published in English and Turkish in electronic databases between January 2012 and November 2023 were examined. International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) Statistics for Macbook (Version 25.0. Armonk, NY, USA) was used for statistical analysis. The Comprehensive Meta-Analysis (CMA) (Version 3.0. Biostat, NJ, USA) program was used for heterogeneity assessment in the articles included in the meta-analysis. After evaluating the studies according to the elimination criteria, 18 original articles were included. Among colistin-resistant strains, blaOXA-51 positivity was 243 (19.61%), blaOXA-23 was 113 (9.12%), blaOXA-58 was 7 (0.56%), blaOXA-143 was 15 (1.21%), and blaOXA-72 was seen in two (0.16%) strains. The positivity rates of pmrA, pmrB, and pmrC were found to be 22 (1.77%), 26 (2.09%), and 6 (0.48%). The mcr-1 rate was found to be 91 (7.34%), the mcr-2 rate was 78 (6.29%), and the mcr-3 rate was 82 (6.61%). The colistin resistance rate in our study was found to be high. However, only some research articles report and/or investigate more than one resistance gene together. Additionally, it may be challenging to explain colistin resistance solely by expressing resistance genes without discussing accompanying components such as efflux pumps, virulence factors, etc.

Investigation of Colistin resistance and method comparison in Klebsiella pneumoniae strains

PurposeThis study aimed to assess the prevalence of colistin resistance in the study group and compare alternative methods with the gold standard. It sought to evaluate the prevalence of plasmid-mediated colistin resistance genes. Material and methodsThe colistin susceptibility of 151 K. pneumoniae strains was determined using Sensititre™, CBDE, ETEST®, and VITEK®2. Results were compared with BMD. The presence of the mcr gene was assessed using polymerase chain reaction. ResultsThe colistin resistance rate was 16,6 %. The categorical agreement of Sensititre™, CBDE, and ETEST® was 100 %. VITEK®2 had a CA of 98 %, a major error of 0.79 %, and a very major error of 8 %. Essential agreement for Sensititre™, ETEST®, and VITEK®2 was 92.7 %, 52.3 %, and 78.1 %, respectively. There were no mcr genes in any strains. ConclusionsDue to the difficulty of applying BMD, colistin resistance data are insufficient globally. Continuous epidemiological studies and validation of alternative methods are needed.

Polymyxin resistance in Enterobacter cloacae complex in Brazil: phenotypic and molecular characterization.

Enterobacter cloacae complex isolates have been reported as an important nosocomial multidrug resistance pathogen. In the present study, we investigated antimicrobial susceptibility and the colistin-resistance rates,their genetic determinants and clonality among clinical E. cloacae complex isolates from different Brazilian states. For this, an initial screening was carried out on 94 clinical isolates of E. clocacae complex received between 2016 and 2018 by LAPIH-FIOCRUZ, using EMB plates containing 4μg/mL of colistin, followed MIC determination, resulting in the selection of 26 colistin-resistant isolates from the complex. The presence of carbapenemases encoding genes (blaKPC, blaNDM and blaOXA-48), plasmidial genes for resistance to polymyxins (mcr1-9) and mutations in chromosomal genes (pmrA, pmrB, phoP and phoQ) described as associated with resistance to polymyxin were screened by PCR and DNA sequencing. Finally, the hsp60 gene was sequenced to identify species of the E. cloacae complex and genetic diversity was evaluated by PFGE and MLST. The results have shown that among 94 E. cloacae complex isolates, 19 (20.2%) were colistin-resistant. The resistant strains exhibited MIC ranging from 4 to 128µg / mL and E. hormaechei subsp. steigerwaltii was the prevalent species in the complex (31,6%), followed by E. cloacae subsp. cloacae (26,3%). The antimicrobials with the highest susceptibility rate were gentamicin (21%) and tigecycline (26%). Carbapenemases encoding genes (blaKPC n = 5, blaNDM n = 1) were detected in 6 isolates and mcr-9 in one. Among the modifications found in PmrA, PmrB, PhoP e PhoQ (two-component regulatory system), only the S175I substitution in PmrB found in E. cloacae subsp cloacae isolates were considered deleterious (according to the prediction of PROVEAN). By PFGE, 13 profiles were found among E. cloacae complex isolates, with EcD the most frequent. Furthermore, by MLST 10 ST's, and 1 new ST, were identified in E. cloacae. In conclusion, no prevalence of clones or association among carbapenemase production and polymyxin resistance was found between the E. cloacae. Thereby, the results suggest that the increased polymyxin-resistance is related to the selective pressure exerted by the indiscriminate use in hospitals. Lastly, this study highlights the urgent need to elucidate the mechanism involved in the resistance to polymyxin in the E. cloacae complex and the development of measures to control and prevent infections caused by these multiresistant bacteria.

An Intra-Hospital Spread of Colistin-Resistant K. pneumoniae Isolates-Epidemiological, Clinical, and Genetic Analysis.

Background and Objective: Klebsiella pneumoniae appears to be a significant problem due to its ability to accumulate antibiotic-resistance genes. After 2013, alarming colistin resistance rates among carbapenem-resistant K. pneumoniae have been reported in the Balkans. The study aims to perform an epidemiological, clinical, and genetic analysis of a local outbreak of COLr CR-Kp. Material and Methods: All carbapenem-resistant and colistin-resistant K. pneumoniae isolates observed among patients in the ICU unit of Military Medical Academy, Sofia, from 1 January to 31 October 2023, were included. The results were analyzed according to the EUCAST criteria. All isolates were screened for blaVIM, blaIMP, blaKPC, blaNDM, and blaOXA-48. Genetic similarity was determined using the Dice coefficient as a similarity measure and the unweighted pair group method with arithmetic mean (UPGMA). mgrB genes and plasmid-mediated colistin resistance determinants (mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5) were investigated. Results: There was a total of 379 multidrug-resistant K. pneumoniae isolates, 88% of which were carbapenem-resistant. Of these, there were nine (2.7%) colistin-resistant isolates in six patients. A time and space cluster for five patients was found. Epidemiology typing showed that two isolates belonged to clone A (pts. 1, 5) and the rest to clone B (pts. 2-4) with 69% similarity. Clone A isolates were coproducers of blaNDM-like and blaOXA-48-like and had mgrB-mediated colistin resistance (40%). Clone B isolates had only blaOXA-48-like and intact mgrB genes. All isolates were negative for mcr-1, -2, -3, -4, and -5 genes. Conclusions: The study describes a within-hospital spread of two clones of COLr CR-Kp with a 60% mortality rate. Clone A isolates were coproducers of NDM-like and OXA-48-like enzymes and had mgrB-mediated colistin resistance. Clone B isolates had only OXA-48-like enzymes and intact mgrB genes. No plasmid-mediated resistance was found. The extremely high mortality rate and limited treatment options warrant strict measures to prevent outbreaks.

Emergence of carbapenem resistant gram-negative pathogens with high rate of colistin resistance in Egypt: A cross sectional study to assess resistance trends during the COVID-19 pandemic

The current study investigated the temporal phenotypic and genotypic antimicrobial resistance (AMR) trends among multi-drug resistant and carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa recovered from Egyptian clinical settings between 2020 and 2021. Bacterial identification and antimicrobial sensitivity of 111 clinical isolates against a panel of antibiotics were performed. Molecular screening for antibiotic resistance determinants along with integrons and associated gene cassettes was implemented. An alarming rate (98.2%) of these isolates were found to be phenotypically resistant to carbapenem. Although 23.9 % K. pneumoniae isolates were phenotypically resistant to colistin, no mobile colistin resistance (mcr) genes were detected. Among carbapenem-resistant isolates, blaNDM and blaOXA-48-like were the most prevalent genetic determinants and were significantly overrepresented among K. pneumoniae. Furthermore, 84.78% of K. pneumoniae isolates co-produced these two carbapenemase genes. The plasmid-mediated quinolone resistance genes (qnrS and qnrB) were detected among the bacterial species and were significantly more prevalent among K. pneumoniae. Moreover, Class 1 integron was detected in 82% of the bacterial isolates. This study alarmingly reveals elevated resistance to last-resort antibiotics such as carbapenems as well as colistin which impose a considerable burden in the health care settings in Egypt. Our future work will implement high throughput sequencing-based antimicrobial resistance surveillance analysis for characterization of novel AMR determinants. This information could be applied as a step forward to establish a robust antibiotic stewardship program in Egyptian clinical settings, thereby addressing the rising challenges of AMR.

Exploring Structure-Activity Relationships of Niclosamide-Based Colistin Potentiators in Colistin-Resistant Gram-Negative Bacteria.

Colistin is primarily used as a last resort antibiotic against highly resistant Gram-negative bacteria (GNB). Rising rates of colistin resistance, however, may limit future use of this agent. The anthelmintic drug niclosamide has been shown to enhance colistin activity in combination therapy, but a detailed structure-activity relationship (SAR) for niclosamide against GNB has yet to be studied. A series of niclosamide analogs were synthesized to perform an SAR, leading to the discovery of a lead compound that displayed comparable colistin-potentiating activity to niclosamide with reduced cytotoxicity. Overall, this work provides important insights into synthetic strategies for the future development of new niclosamide derivatives and demonstrates that toxicity to mammalian cells can be reduced while maintaining colistin potentiation.

Colistin Resistance among Enterobacterales Isolates: Underlying Mechanisms and Alternative Treatment Options

Global dissemination of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB) such as carbapenemase-producing Enterobacterales has resulted in reviving colistin as a final therapeutic alternative. Colistin resistance foretold a catastrophe. We aimed to detect the rates of carbapenems and colistin resistance among hospital-acquired Enterobacterales species, verify the underlying mechanisms and provide antibiogram for colistin-resistant isolates. The collected Enterobacterales isolates were tested for their antimicrobial susceptibility by the disk diffusion method and agar dilution was utilized for both imipenem and colistin. The production of ESβLs and carbapenemases was phenotypically assessed by the combined disk (CDT) and modified carbapenem inactivation (mCIM) tests, respectively. Possible attributes for colistin resistance were explored by detection of both plasmid- and efflux pump-mediated mechanisms. By multiplex PCR assay, carbapenem resistance (blaNDM-1 & blaOXA-48) and mobilized colistin-resistant-1 (mcr-1) genes were identified. A total of 160 Enterobacterales isolates were obtained of which 68.8% were MDR, 25% were XDR and 6.3% were pandrug-resistant (PDR) isolates with no statistically significant difference among Enterobacterales species (P> 0.05). Carbapenems resistance was detected in 41.3% (66/160) while colistin resistance was detected in 22% (36/160) of isolates. Proteus mirabilis expressed the highest rate of colistin resistance (100%; 16/16), followed by Enterobacter aerogenes (23.1%; 6/26), E. coli (13%; 6/46) and K.pneumoniae (11.1%; 8/72). One hundred percent (36/36) of colistin-resistant isolates proved efflux pump activity for colistin. However; only 2% (2/100) of tested Enterobacterales carried mcr-1 gene through molecular analysis. Colistin-resistant isolates exhibited variable susceptibility to the tested antimicrobial agents of which fosfomycin was the highest (94.1%). Efflux pump activity played a major role for colistin resistance among Enterobacterales species and fosfomycin could be a promising therapeutic option.

Roles of crrAB two-component regulatory system in Klebsiella pneumoniae: growth yield, survival in initial colistin treatment stage, and virulence

Alternation of the colistin resistance-regulating two-component regulatory system (crrAB) is a colistin-resistance mechanism in Klebsiella pneumoniae (K. pneumoniae), but its role in bacteria is not fully understood. Twelve colistin-susceptible K. pneumoniae clinical isolates were included in this study: six crrAB-positive and six crrAB-negative. We deleted the crrAB genes from two crrAB-positive isolates and complemented them. We measured the growth yields by determining growth curves in lysogeny broth and minimal media with or without Fe2+. In vitro selection rates for colistin resistance were determined by exposure to colistin, and survival rates against high concentrations of colistin (20 mg/L) at the early stage of growth (20 min) were investigated. Virulence was determined using a serum bactericidal assay and Galleria mellonella larval infection. The presence of crrAB was not associated with colistin resistance and did not increase the in vitro selection rate of colistin resistance after exposure. The growth yield of crrAB-positive isolates was higher in lysogeny broth media and increased when Fe2+ was added to minimal media. The crrAB-positive isolates showed higher survival rates in the early stages of exposure to high colistin concentrations. Decreased serum resistance was identified in the crrAB-deleted mutants. More G. mellonella larvae survived when infected by crrAB-deleted mutants, and higher survival rates of bacteria were identified within the larvae infected with wild-type than crrAB-deletant isolates. Through rapid response to external signals, crrAB would provide advantages for K. pneumoniae survival by increasing the final growth yield and initial survival against colistin treatment. This may partly contribute to the bacterial virulence.

Investigation of Virulence Factors and Antibiotic Resistance of Pseudomonas aeruginosa Isolated from A Range of Clinical Samples

Objective: Pseudomonas aeruginosa is an opportunistic pathogen, is one of the leading nosocomial infection-causing agents and over time has developed multidrug resistance. One of the most common patient groups affected by P. aeruginosa are on the intensive care unit (ICU), an optimal environment for the development of antibiotic resistance. The aim of this study was to investigate virulence factors and antibiotic resistance profiles of P. aeruginosa isolated from hospitalized patients in Turkey. Methods: Samples from the general wards and ICU-hospitalized patients were included. A nutrient agar-elastin method was used for the biochemical activity of elastase. For las B assessment PCR was used while special production medium was used to assay pyoverdine and pyocyanin. Isolate biofilm production was tested with the crystal violet method. Standard broth microdilution was used for antibiotic susceptibility. Results: A total of 208 samples were assessed. The virulence factor frequencies in ICU and ward isolates, were: pyocyanin 86.2% and 86.7%, pyoverdine 90.1%, and 89.6%, elastase 68.6% and 67.9%, las B 93.1% and 89.6%, and biofilm production 51.9% and 48.1%, respectively. Antibiotic resistance rates in ICU and ward were: meropenem 41.1% and 28.9%, colistin 11.7% and 13.2%, ceftazidime 43.1%,and 41.1%, and cefepime 52.9% and 48.5%. Conclusion: Virulence factors were present in most of the hospitalized patient samples. However, antibiotic resistance rates were below 50%, except for cefepime. In addition, low rates of colistin resistance suggest that colistin resistance is not yet widespread in our hospital.

Emerging Increase in Colistin Resistance Rates in Escherichia coli and Salmonella enterica from Türkiye.

Foodborne infections caused by drug-resistant Salmonella spp. are a global health concern. Moreover, commensal Escherichia coli is considered risky due to the presence of antimicrobial resistance genes. Colistin is considered a last-resort antibiotic against Gram-negative bacterial infections. Colistin resistance can be transferred both vertically, and horizontally via conjugation between bacterial species. Plasmid-mediated resistance has been associated with mcr-1 to mcr-10 genes. In this study, we collected food samples (n = 238), and isolated E. coli (n = 36) and Salmonella (n = 16), representing recent isolates. We included previously collected Salmonella (n = 197) and E. coli (n = 56) from various sources from 2010 to 2015 in Türkiye as representing historical isolates to investigate colistin-resistance over time. In all isolates, colistin resistance was screened phenotypically by minimum inhibitory concentration (MIC), and then in resistant isolates, mcr-1 to mcr-5 genes were further screened. In addition, the antibiotic resistance of recent isolates was determined, and antibiotic resistance genes were investigated. We found that in total 20 Salmonella isolates (9.38%) and 23 of the E. coli isolates (25%) showed phenotypic colistin resistance. Interestingly, the majority of colistin-resistant isolates (N:32) had resistance levels above 128mg/L. Furthermore 75% of commensal E. coli isolates recently isolated were resistant at least 3 antibiotics. Overall, we found that the colistin resistance has been increased from 8.12 to 25% in Salmonella isolates, and 7.14% to 52.8% in E. coli isolates over time. However, none of these resistant isolates carried mcr genes, most likely indicating emerging chromosomal colistin resistance.

Genomics of Aminoglycoside Resistance in Pseudomonas aeruginosa Bloodstream Infections at a United States Academic Hospital.

Pseudomonas aeruginosa frequently becomes resistant to aminoglycosides by the acquisition of aminoglycoside modifying enzyme (AME) genes and the occurrence of mutations in the mexZ, fusA1, parRS, and armZ genes. We examined resistance to aminoglycosides in a collection of 227 P. aeruginosa bloodstream isolates collected over 2 decades from a single United States academic medical institution. Resistance rates of tobramycin and amikacin were relatively stable over this time, while the resistance rates of gentamicin were somewhat more variable. For comparison, we examined resistance rates to piperacillin-tazobactam, cefepime, meropenem, ciprofloxacin, and colistin. Resistance rates to the first four antibiotics were also stable, although uniformly higher for ciprofloxacin. Colistin resistance rates were initially quite low, rose substantially, and then began to decrease at the end of the study. Clinically relevant AME genes were identified in 14% of isolates, and mutations predicted to cause resistance were relatively common in the mexZ and armZ genes. In a regression analysis, resistance to gentamicin was associated with the presence of at least one gentamicin-active AME gene and significant mutations in mexZ, parS, and fusA1. Resistance to tobramycin was associated with the presence of at least one tobramycin-active AME gene. An extensively drug-resistant strain, PS1871, was examined further and found to contain five AME genes, most of which were within clusters of antibiotic resistance genes embedded in transposable elements. These findings demonstrate the relative contributions of aminoglycoside resistance determinants to P. aeruginosa susceptibilities at a United States medical center. IMPORTANCE Pseudomonas aeruginosa is frequently resistant to multiple antibiotics, including aminoglycosides. The rates of resistance to aminoglycosides in bloodstream isolates collected over 2 decades at a United States hospital remained constant, suggesting that antibiotic stewardship programs may be effective in countering an increase in resistance. Mutations in the mexZ, fusA1, parR, pasS, and armZ genes were more common than acquisition of genes encoding aminoglycoside modifying enzymes. The whole-genome sequence of an extensively drug resistant isolate indicates that resistance mechanisms can accumulate in a single strain. Together, these results suggest that aminoglycoside resistance in P. aeruginosa remains problematic and confirm known resistance mechanisms that can be targeted for the development of novel therapeutics.

Fecal carriage and molecular epidemiology of mcr-1-harboring Escherichia coli from children in southern China

BackgroundThe increase of multidrug-resistant Enterobacteriaceae bacteria has led to the reintroduction of colistin for clinical treatments, and colistin has become a last resort for infections caused by multidrug-resistant bacteria. Enterobacteriaceae bacteria carrying the mcr-1 gene are majorly related to colistin resistance, which may be the main reason for the continued increase in the colistin resistance rate of Enterobacteriaceae. The study aimed to investigate the sequence type and prevalence of Escherichia coli (E. coli) harboring the mcr-1 gene in the gut flora of children in southern China. MethodsFecal samples (n = 2632) of children from three medical centers in Guangzhou were cultured for E. coli. The mcr-1-harboring isolates were screened via polymerase chain reaction (PCR). The colistin resistance transfer frequency was studied by conjugation experiments. DNA sequencing data of seven housekeeping genes were used for multi-locus sequence typing analysis (MLST). ResultsPCR indicated that 21 of the 2632 E. coli (0.80%) isolates were positive for mcr-1; these strains were resistant to colistin. Conjugation experiments indicated that 18 mcr-1-harboring isolates could transfer colistin resistance phenotypes to E. coli J53. MLST analysis revealed that the 21 isolates were divided into 18 sequence types (STs); E. coli ST69 was the most common (14.3%), followed by E. coli ST58 (9.5%). ConclusionThese results demonstrate the colonization dynamics and molecular epidemiology of E. coli harboring mcr-1 in the gut flora of children in southern China. The mcr-1 gene can be horizontally transmitted within species; hence, it is necessary to monitor bacteria that harbor mcr-1 in children.

Efficacy of Colistin Therapy in Patients with Hematological Malignancies: What if There is Colistin Resistance?

Objective: The objective of this study was to evaluate the clinical efficacy and appropriateness of colistin therapy in patients with hematological malignancies. Methods: Age, gender, type of hematologic malignancy, and potential carbapenem-resistant microorganism risk factors were all noted in this retrospective study. In empirical and agent-specific treatment groups, differences in demographic features, risk factors, treatment responses, and side effects were compared. Results: Sixty-three patients were included, 54% were male, and the median age was 49. In the last three months, the hospitalization rate history was 68%, and four patients had a hospitalization history in the ICU. Carbapenem-resistant K. pneumoniae colonization was present in 22 patients (35%). Gram-negative microorganisms were isolated in 34 patients (54%). The carbapenem, quinolone, and colistin resistance rates were 82%, 76%, and 4% respectively. Clinical and microbiological response rates were 60% and 69%. 7 and 28-day mortality rates were 17% and 35%. There was no significant difference in demographic data and comorbidities in empirical (n=48) and agent-specific (n=15) treatment groups. The rate of carbapenem and glycopeptide treatments before colistin was higher in the empirical treatment group (p = 0.004; p = 0.001). The rate of starting combined antibiotics was higher inthe empirical treatment group (p = 0.016). Two of the patients developed renal failure in the first week after treatment. Conclusion: The use of empirical colistin may be unavoidable given the risk considerations. Shortly, colistin-resistant strains may also be a factor affecting treatment success negatively.

SG-APSIC1102: Antimicrobial resistance and related factors in an intensive care unit—A study at Hue Central Hospital

Objectives: Antimicrobial resistance (AMR) has emerged as a major concern in Vietnam, mainly due to the inappropriate use of antibiotics. Appropriate antibiotic management enables us to minimize the likelihood of antibiotic resistance and the spread of resistant bacteria. We evaluated vancomycin and colistin resistance and related factors in the intensive care unit (ICU) of Hue Central Hospital, a national hospital in central Vietnam. Methods: Using a cross-sectional descriptive study, we enrolled 362 patients who were prescribed antibiotics and were admitted to the ICU in 2019. Pathogens isolated from 473 routine clinical samples were subjected to antimicrobial susceptibility testing following the recommendations in the Clinical & Laboratory Standards Institute M100, 28thEdition. Colistin testing was performed using the broth microdilution method. Statistical significance was determined using the Fisher exact test. Results: The most commonly identified microorganisms were Acinetobacter baumannii (31.5%), Klebsiella pneumoniae (31.2%), Pseudomonas aeruginosa (12%), and Staphylococcus aureus (8.9%). All isolates of A. baumannii, K. pneumoniae, and P. aeruginosa tested with colistin were nonresistant. Moreover, >65% of A. baumannii isolates were resistant to all antibiotics except colistin. S. aureus had the highest resistance rate to erythromycin (80.6%), but no vancomycin-resistant isolates were identified. Factors associated with resistance to at least 1 antibiotic tested included length of stay (OR, 5.32; 95% CI, 1.47–19.17; P = .017), duration of antibiotics therapy (OR, 5.25; 95% CI, 1.46–18.95; P = .017), and the use of tracheal intubation and ventilator (OR, 3.08; 95% CI, 1.09–8.72; P = .038). Conclusions: These data indicated that although the vancomycin and colistin resistance rate is low, patients with longer length of stay, longer time on antibiotics, and invasive ventilation were at higher risk of AMR infection. Decreasing device use and strong antibiotic stewardship program at the hospital would help to reduce AMR infections.

Dissemination of Metallo-β-Lactamase-Producing Pseudomonas aeruginosa in Serbian Hospital Settings: Expansion of ST235 and ST654 Clones.

This nationwide study aimed to investigate the molecular characteristics of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa in Serbia, underlying resistance mechanisms, the genetic context of detected MBL genes, and the clonal relationship between isolates harboring genes-encoding MBL. Overall, 320/5334 isolates collected from 2018 to 2021 were identified as P. aeruginosa. Carbapenem-resistant P. aeruginosa (CRPA) were screened for the presence of blaVIM, blaIMP, and blaNDM, genes whereas MBL-positive isolates were tested for the presence of the blaCTX-M-2, blaPER, blaTEM, blaSHV, blaVEB, and blaGES. Multilocus sequence typing and phylogenomic analysis were performed for P. aeruginosa-producing MBL. The majority of the P. aeruginosa isolates were recovered from the lower respiratory tract (n = 120; 37.5%) and wound specimens (n = 108; 33.75%). CRPA isolates accounted for 43.1% (n = 138) of the tested isolates, 31 out of them being blaNDM-1-positive (22.5%). The colistin resistance rate was 0.3%. MLST analysis revealed the occurrence of ST235 (n = 25) and ST654 (n = 6), mostly confined to Serbia. The distribution of beta-lactamase-encoding genes in these isolates suggested clonal dissemination and possible recombination: ST235/blaNDM-1, ST235/blaNDM-1/blaPER-1, ST654/blaNDM-1, ST654/blaNDM-1/blaPER-1, and ST654/blaNDM-1/blaGES-5. High-risk clones ST235 and ST654 identified for the first time in Serbia, are important vectors of acquired MBL and ESBL and their associated multidrug resistance phenotypes represent a cause for considerable concern.

Can colistin susceptibility results determined in multidrug resistant Gram-negative bacteria be used for polymyxin B?

Abstract Introduction The present study aimed to compare the MIC values of colistin and polymyxin B in fermentative and non-fermentative Gram-negative bacteria and to examine whether the susceptibility results determined with colistin can be used for polymyxin B. Materials and Methods A total of 268 strains of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa (P. aeruginosa), and Acinetobacter baumannii (A. baumannii) isolates were included in the study. The reference broth microdilution and the results were evaluated according to CLSI recommendations. Results Of the 268 strains, 40.7% were found to be colistin resistant and 34% polymyxin B resistant. Essential agreement (EA) and categorical agreement (CA) ratios for all isolates were found to be 81.3% and 85.1%, respectively. Identical MIC values were found for colistin and polymyxin B in 104 isolates (38.8%), and this rate was 31.1% and 48.7% in Enterobacterales and non-fermentative bacteria, respectively. Colistin resistance rates were 25.4% for E. coli, 67.4% for K. pneumoniae, 23.8% for P. aeruginosa, and 31.5% for A. baumannii. Polymyxin B resistance rates were 18.6% for E. coli, 64.1% for K. pneumoniae, 19% for P. aeruginosa, and 16.7% for A. baumannii. Conclusion According to the results of the study, it was concluded that the MIC values of colistin and polymyxin B antibiotics in all bacteria were not compatible with each other. Colistin susceptibility results cannot be used for treatment with polymyxin B, despite CLSI's recommendation.

The role of pmrCAB genes in colistin-resistant Acinetobacter baumannii

The progressively increasing antimicrobial-resistant Acinetobacter baumannii infections have enforced the use of colistin as the last option for therapy, resulting in the colistin resistance evolution. This work aimed to study the pmrCAB expression in A. baumannii isolates as well as the presence of the mcr-1 gene. Colistin MICs of 100 A. baumannii isolates were measured using the broth microdilution assay. In four colistin-susceptible and four colistin-resistant isolates, the relative expression of the pmrA, pmrB, and pmrC genes was determined using reverse transcription PCR, and then selected isolates were sequenced using the Sanger technique. Finally, the mcr-1 gene was detected using conventional PCR. The colistin resistance rate among the studied isolates was 49%. The expression levels of pmrA and pmrB were statistically significantly higher in colistin-resistant isolates than in colistin-susceptible ones, while the pmrC expression had no statistically significant change. There was a weak positive correlation between colistin MICs and the expression levels of each of the pmrA and pmrB genes. By sequencing, two colistin-resistant strains with low pmrCAB expression showed insertion mutations 3277188_3277189T in pmrB and 1185149_1185150T in pmrC. Only one isolate (1%) was positive for the presence of mcr-1. We concluded that pmrCAB increased expression and/or mutations may cause colistin resistance in A. baumannii. However, increased pmrC expression may not necessarily result in colistin resistance. In Egypt, this is the first study to reveal the existence of mcr-1 in A. baumanni. This should attract attention in clinical settings due to the ultimate tendency of spreading colistin resistance.

Increasing trends of colistin resistance in patients at high-risk of carbapenem-resistant Enterobacteriaceae

Introduction Occurrence of colistin-resistant Enterobacteriaceae in response to the unregulated use of this antibiotic has been documented. This study reports an investigation of colistin resistance rates among carbapenem-resistant enterobacterial clinical isolates. Methods A total of 196 multidrug-resistant Enterobacteriaceae isolates (Klebsiella pneumoniae (n = 100), Escherichia coli (n = 89) and Enterobacter cloacae (n = 7) were selected from Gram-negative isolates over one year. Susceptibility to antimicrobials was determined using Vitek2. Broth microdilution method was used to detect colistin antimicrobial susceptibility. Identification of ESBL and carbapenemases were both done phenotypically and by PCR. Results All the studied isolates showed multidrug-resistant phenotypes with 51.5% resistance to carbapenems (meropenem, imipenem). Very low resistance rates towards tigecycline (n = 9) 4.6% were found. Thirty-nine isolates (19.9%) showed reduced susceptibility to colistin among the MDR isolates. Sixty-four isolates (32.7%) were ESBL producers. Hundred isolates (51%) were carbapenemase producers using Carba NP test. The PCR amplification results revealed that 40 isolates (20%) harboured NDM-1 and 40 isolates contained OXA-48-like gene. Coexistence of both (NDM-1 and OXA-48-like) was observed in nine (4.59%) isolates. A Statistically significant relationship was observed between carbapenem resistance and each of the followings; OXA-48 producers (p= .009), amikacin resistance (p = .000), gentamicin resistance (p = .032), tobramycin resistance (p = .000), and tigecycline resistance (p-value ≤ .001). A statistical significance was detected between ESBL-producing isolates and carbapenem susceptible isolates ESBL producers with p = 0.000. Conclusion An alarming sign is the increasing colistin resistance rates among carbapenem-resistant isolates. Aminoglycosides are still a therapeutic option to decrease the use of colistin and avoid further development of resistance. KEY MESSAGES High rates of colistin resistance among carbapenem-resistant Enterobacteriaceae. The choice of antibiotic is significantly associated with the clinical site of infection. Aminoglycosides are offered choices for treating multiple drug-resistant Enterobacteriaceae to preserve the colistin and carbapenems.

Antibiotic Resistance, Molecular Characteristics and Risk Factors of Carbapenem-Resistant Klebsiella pneumoniae in Clinical Isolates.

The global epidemic of carbapenem-resistant Klebsiella pneumonia (CRKP) has becomea significant public health challenge. This study aimed to investigate the antibiotic resistance and molecular characteristics of CRKP and the clinical characteristics of infected patients. Sixty-two clinically isolated CRKP strains were collected for the first time from the First Affiliated Hospital of Zhejiang Chinese Medical University in Zhejiang Province. The carbapenemase gene, virulence-associated gene, capsular serotype gene and fenestra protein gene were detected by PCR. Univariate logistic regression and multivariate logistic regression analyses were performed to predict the risk factors for the prognosis of CRKP infection. All CRKP isolates were resistant to meropenem, piperacillin-tazobactam, and ceftazidime (100%, 62/62), and all but one CRKP isolate was resistant to imipenem and cefepime (96.8%, 61/62). The rate of colistin resistance was the lowest (11.9%, 8/62). For CRKP in the ICU, the rates of resistance to various antibiotics were significantly higher than those in general ward patients. Fifty strains carried the carbapenemase gene bla KPC, and 3 strains carried both the bla KPC and bla NDM genes. The virulence genes uge, wabG, ycf, entB, ureA and fimH were detected in more than 90% of the 62 CRKP strains. Two strains had Ompk35, Ompk36 and Hcp gene deletions. The bla KPC, rmpA and rmpA2 genes had the highest positive rate in blood samples, and bla NDM had the highest positive rate in stool samples. Multivariate analysis showed that pulmonary disease affected the prognosis of CRKP infection. The prevalence and molecular characteristics of CRKP clinical isolates in Zhengjiang Province in China were described, and the antibiotic resistance rate was higher. Additionally, relevant genes of CRKP strains and clinical characteristics of patients are related to the progression and prognosis of CRKP infection.

Global Prevalence of Colistin Resistance in Klebsiella pneumoniae from Bloodstream Infection: A Systematic Review and Meta-Analysis.

Background: Among gram-negative bacteria, Klebsiella pneumoniae is one of the most common causes of healthcare-related infection. Bloodstream infections (BSIs) caused by Klebsiella pneumoniae are notorious for being difficult to treat due to resistance to commonly used antimicrobials. Klebsiella pneumoniae isolates from bloodstream infections are becoming increasingly resistant to carbapenems. In the fight against carbapenem-resistant Klebsiella pneumoniae, colistin [polymyxin E] is the antimicrobial of choice and is thus widely used. Objective: This study aimed to determine the global prevalence of colistin resistance amongst Klebsiella pneumoniae isolates from bloodstream infections. Methods: PubMed, Medline, Scopus, and the Cochrane Library were searched for published articles without restricting the search period. Studies meeting the predefined inclusion and exclusion criteria were included, and quality was assessed using Joanna Briggs Institute Checklist. We used a statistical random effect model to analyze data with substantial heterogeneity (I2 > 50%) in the meta-analysis. Results: A total of 10 studies out of 2873 search results that met the inclusion criteria were included in the final synthesis for this study. A pooled prevalence of colistin resistance was 3.1%, 95% CI (1.5–4.7%). The highest colistin resistance pooled prevalence was recorded in isolates studied in 2020 and beyond 12.90% (4/31), while Klebsiella pneumoniae isolates studied in 2015 and before and in 2016–2019 showed a pooled colistin resistance rate of 2.89% (48/1661) and 2.95% (28/948), respectively. The highest colistin resistance was found in Klebsiella pneumoniae isolates from Thailand (19.2%), while the least pooled resistance was in Klebsiella pneumoniae from South Korea (0.8%). The pooled prevalence of the multidrug-resistant (MDR) of Klebsiella pneumoniae from bloodstream infection ranged from 80.1%, 95% CI (65.0–95.2%), and the resistance prevalence of other antibiotics by Klebsiella pneumoniae from bloodstream infections were as follows; ciprofloxacin (45.3%), ertapenem (44.4%), meropenem (36.1%), imipenem (35.2%), gentamicin (33.3%), amikacin (25.4%) and tigecycline (5.1%). Klebsiella pneumoniae recovered from the intensive care unit (ICU) showed higher colistin resistance, 11.5% (9/781%), while non-ICU patients showed 3.03% (80/2604) pooled colistin resistance. Conclusion: This study showed low colistin resistance in Klebsiella pneumoniae isolates from global bloodstream infections. However, significant colistin resistance was observed in isolates collected from 2020 and beyond. Significant colistin resistance was also observed in Klebsiella pneumoniae isolates in bloodstream infections from the intensive care unit (ICU) compared to those from non-ICUs. As a result, there is a need to institute colistin administration stewardship in the ICU in clinical settings.