Antimicrobial susceptibility and mechanisms of resistance to quinolones and beta-lactams in Acinetobacter genospecies 3.
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ABSTRACT:
SUBMITTER: Ribera A
PROVIDER: S-EPMC375291 | biostudies-literature | 2004 Apr
REPOSITORIES: biostudies-literature
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Project description:Whole genome sequencing of Acinetobacter genospecies, an opportunistic pathogen
| PRJDB2309 | ENA
Project description:The study investigated the effect of antibiotic combinations against 20 clinical isolates of A. baumannii (seven colistin-resistant and 13 colistin-susceptible) with different resistance mechanisms. Clinical data, treatment, and patient mortality were evaluated. The following methods were used: MIC, PCRs, and outer membrane protein (OMP) analysis. Synergy was investigated using the checkerboard and time-kill methods. Clonality was evaluated by PFGE. Based on clonality, the whole genome sequence of six A. baumannii isolates was analyzed. All isolates were resistant to meropenem, rifampicin, and fosfomycin. OXA-23 and OXA-143 were the most frequent carbapenemases found. Four isolates showed loss of a 43kDa OMP. The colistin-susceptible isolates belonged to different clones and showed the highest synergistic effect with fosfomycin-amikacin. Among colistin-resistant isolates, the highest synergistic effect was observed with the combinations of colistin-rifampicin followed by colistin-vancomycin. All colistin-resistant isolates harbored blaOXA-23-like and belonged to CC113. Clinical and demographic data were available for 18 of 20 patients. Fourteen received treatment and eight patients died during treatment. The most frequent site of infection was the blood in 13 of 14 patients. Seven patients received vancomycin plus an active drug against A. baumannii; however, mortality did not differ in this group. The synergistic effect was similar for colistin-susceptible isolates of distinct clonal origin presenting with the same resistance mechanism. Overall mortality and death during treatment was high, and despite the high synergism in vitro with vancomycin, death did not differ comparing the use or not of vancomycin plus an active drug against A. baumannii.
| S-EPMC4801211 | biostudies-literature
Project description:The stringent response regulators, (p)ppGpp and DksA, modulate various genes involved in physiological processes, virulence, and antimicrobial resistance in pathogenic bacteria. This study investigated the role of DksA in the antimicrobial susceptibility of Acinetobacter baumannii. The ∆dksA mutant (KM0248D) of A. baumannii ATCC 17978 and its complemented strain (KM0248C) were used, in addition to the ∆dksA mutant strain (NY0298D) of clinical 1656-2 strain. The microdilution assay was used to determine the minimum inhibitory concentrations (MICs) of antimicrobial agents. Quantitative real-time PCR was performed to analyze the expression of genes associated with efflux pumps. The KM0248D strain exhibited an increase of MICs to quinolones and tetracyclines, whereas KM0248D and NY0298D strains exhibited a decrease of MICs to aminoglycosides. The expression of genes associated with efflux pumps, including adeB, adeI/J, abeM, and/or tetA, was upregulated in both ∆dksA mutant strains. The deletion of dksA altered bacterial morphology in the clinical 1656-2 strain. In conclusion, DksA modulates the antimicrobial susceptibility of A. baumannii. The ∆dksA mutant strains of A. baumannii upregulate efflux pump gene expression, whereas (p)ppGpp-deficient mutants downregulate efflux pump gene expression. (p)ppGpp and DksA conduct opposite roles in the antimicrobial susceptibility of A. baumannii via efflux pump gene regulation.
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Project description:Corynebacterium urealyticum is a non-diphtherial urease-producing clinically relevant corynebacterial, most frequently involved in urinary tract infections. Most of the C. urealyticum clinical isolates are frequently resistant to several antibiotics. We investigated the susceptibility of 40 C. urealyticum isolated in our institution during the period 2005-2017 to eight compounds representative of the main clinically relevant classes of antimicrobial agents. Antimicrobial susceptibility was determined by the Epsilometer test. Resistance genes were searched by PCR. All strains were susceptible to vancomycin whereas linezolid and rifampicin also showed good activity (MICs90 = 1 and 0.4 mg/L, respectively). Almost all isolates (39/40, 97.5%) were multidrug resistant. The highest resistance rate was observed for ampicillin (100%), followed by erythromycin (95%) and levofloxacin (95%). Ampicillin resistance was associated with the presence of the blaA gene, encoding a class A β-lactamase. The two rifampicin-resistant strains showed point mutations driving amino acid replacements in conserved residues of RNA polymerase subunit β (RpoB). Tetracycline resistance was due to an efflux-mediated mechanism. Thirty-nine PFGE patterns were identified among the 40 C. urealyticum, indicating that they were not clonally related, but producing sporadic infections. These findings raise the need of maintaining surveillance strategies among this multidrug resistant pathogen.
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Project description:Acinetobacter spp. are important nosocomial pathogens, in particular the Acinetobacter baumannii-calcoaceticus complex, which have become a global public health threat due to increasing resistance to carbapenems and almost all other antimicrobial compounds. High rates of resistance have been reported among countries in Southeast Asia, including Malaysia. In this review, we examine the antimicrobial resistance profiles of Acinetobacter spp. hospital isolates from Malaysia over a period of nearly three decades (1987-2016) with data obtained from various peer-reviewed publications as well as the Malaysian National Surveillance on Antibiotic Resistance (NSAR). NSAR data indicated that for most antimicrobial compounds, including carbapenems, the peak resistance rates were reached around 2008-2009 and thereafter, rates have remained fairly constant (e.g., 50-60% for carbapenems). Individual reports from various hospitals in Peninsular Malaysia do not always reflect the nationwide resistance rates and often showed higher rates of resistance. We also reviewed the epidemiology and mechanisms of resistance that have been investigated in Malaysian Acinetobacter spp. isolates, particularly carbapenem resistance and found that blaOXA-23 is the most prevalent acquired carbapenemase-encoding gene. From the very few published reports and whole genome sequences that are available, most of the Acinetobacter spp. isolates from Malaysia belonged to the Global Clone 2 (GC2) CC92 group with ST195 being the predominant sequence type. The quality of data and analysis in the national surveillance reports could be improved and more molecular epidemiology and genomics studies need to be carried out for further in-depth understanding of Malaysian Acinetobacter spp. isolates.
| S-EPMC5733036 | biostudies-literature
Project description:Antimicrobial resistance is mostly studied by means of phenotypic growth inhibition determinations, in combination with PCR confirmations or further characterization by means of whole genome sequencing (WGS). However, the actual proteins that cause resistance such as enzymes and a lack of porins cannot be detected by these methods. Improvements in liquid chromatography (LC) and mass spectrometry (MS) enabled easier and more comprehensive proteome analysis. In the current study, susceptibility testing, WGS and MS are combined into a multi-omics approach to analyze resistance against frequently used antibiotics within the beta-lactam, aminoglycoside and fluoroquinolone group in E. coli and K. pneumoniae. Our aim was to study which currently known mechanisms of resistance can be detected at the protein level using liquid chromatography-mass spectrometry (LC-MS/MS) and to assess whether these could explain beta-lactam, aminoglycoside, and fluoroquinolone resistance in the studied isolates. Furthermore, we aimed to identify significant protein to resistance correlations which have not yet been described before and to correlate the abundance of different porins in relation to resistance to different classes of antibiotics. Whole genome sequencing, high-resolution LC-MS/MS and antimicrobial susceptibility testing by broth microdilution were performed for 187 clinical E. coli and K. pneumoniae isolates. Resistance genes and proteins were identified using the Comprehensive Antibiotic Resistance Database (CARD). All proteins were annotated using the NCBI RefSeq database and Prokka. Proteins of small spectrum beta-lactamases, extended spectrum beta-lactamases, AmpC beta-lactamases, carbapenemases, and proteins of 16S ribosomal RNA methyltransferases and aminoglycoside acetyltransferases can be detected in E. coli and K. pneumoniae by LC-MS/MS. The detected mechanisms matched with the phenotype in the majority of isolates. Differences in the abundance and the primary structure of other proteins such as porins also correlated with resistance. LC-MS/MS is a different and complementary method which can be used to characterize antimicrobial resistance in detail as not only the primary resistance causing mechanisms are detected, but also secondary enhancing resistance mechanisms.
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Project description:The intensive and extensive broiler production systems imply different veterinary interventions, including the use of antimicrobials. This study aimed to compare the antimicrobial susceptibility profiles of Escherichia coli isolated from both systems, characterize resistance mechanisms to β-lactams and polymyxins, and identify genetic elements such as integrons. E. coli isolates recovered from broiler cecal samples were assayed for antimicrobial susceptibility through the broth microdilution technique. The molecular characterization of acquired resistance mechanisms to β-lactams and colistin and the detection of integrons was performed by a multiplex PCR. For most antibiotics tested, the prevalence of reduced susceptibility is higher in commensal and extended-spectrum β-lactamases (ESBL)/AmpC producers from broilers raised in the intensive system, compared with those raised under extensive conditions. SHV-12 was the most common ESBL enzyme found in both production systems. Other ESBL variants such as CTX-M-1, CTX-M-55, CTX-M-14, CTX-M-32, CTX-M-9, TEM-52, and plasmid-encoded AmpC enzyme CMY-2 were also present. MCR-1 was identified in a colistin-resistant isolate from broilers raised under the intensive system. This study highlights the differences in E. coli antibiotic susceptibility from both production types and emphasizes that a great deal of work remains to decrease consumption and antimicrobial resistance levels.
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Project description:Multidrug resistance (MDR) is one of the deadliest public health concerns of the 21st century, rendering many powerful antibiotics ineffective. The current study provides important insights into the prevalence and mechanisms of antibiotic resistance in hospital wastewater isolates. In this study, we determined the MDR profile of 68 bacterial isolates collected from five different hospitals in Dhaka, Bangladesh. Of them, 48 bacterial isolates were identified as Enterobacteriaceae. Additionally, we investigated the prevalence and distribution of five beta-lactam resistance genes, as well as quinolone resistance mechanisms among the isolates. The results of this study showed that 87% of the wastewater isolates were resistant to at least three different antibiotic classes, as revealed using the disc diffusion method. Resistance to β-lactams was the most common, with 88.24% of the isolates being resistant, closely followed by macrolides (80.88% resistant). Polymyxin was found to be the most effective against wastewater isolates, with 29.41% resistant isolates. The most common β-lactam resistance genes found in wastewater isolates were blaTEM (76.09%), blaCTX-M1 (71.74%), and blaNDM (67.39%). Two missense mutations in the quinolone resistance-determining region (QRDR) of gyrA (S83L and D87N) and one in both parC (S80I) and parE (S458A) were identified in all isolates, and one in parE (I529L), which had not previously been identified in Bangladesh. These findings suggest that hospital wastewater acts as an important reservoir of antibiotic-resistant bacteria wherein resistance mechanisms to β-lactams and fluoroquinolones are obvious. Our data also emphasize the need for establishing a nationwide surveillance system for antibiotic resistance monitoring to ensure that hospitals sanitize their wastewater before disposal, and regulation to ensure hospital wastewater is kept away from community settings.
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| S-EPMC2876422 | biostudies-literature
Project description:The adherent invasive Escherichia coli (AIEC) pathotype has been associated with the aetiology of Crohn's disease (CD). Scarce reports have shown the antimicrobial resistance (AMR) profiles of AIEC. Despite antibiotics not being recommended to treat CD, antimicrobial therapy could be useful in stratified patients, such as AIEC carriers. We examined the antimicrobial resistance profiles of AIEC strains to identify which therapies could be effective or confer a risk for such patients. Phenotypic resistance to 30 antimicrobials was tested according to CLSI standards. AIEC (n = 22) and non-pathogenic E. coli (non-AIEC) strains (n = 37) isolated from the gut mucosa of 31 CD patients and 18 controls were studied. De novo genome sequencing was carried out for 39 of the 59 strains, and AMR genes were searched using the DeepARG database in these genomes and 33 additional AIEC publicly available genomes. The strains isolated from CD and controls showed similar phenotypic AMR profiles. The genomic analysis did not reveal an increased prevalence of AMR genes. However, AIEC strains were more frequently resistant to ?-lactams than non-AIEC strains (11 AIEC (50%) and 5 non-AIEC (22%) strains were resistant to at least one ?-lactam; p < 0.042). Two AIEC strains were resistant to expanded-spectrum cephalosporins. One strain carried a plasmid-mediated AmpC ?-lactamase (CMY-69), and the other presented mutations in the promotor of the intrinsic chromosomal AmpC related to the hyperproduction of this enzyme. The rest of the strains were resistant to ?-lactams not including expanded-spectrum cephalosporins. The majority carried TEM-related ?-lactamases. Genomic analysis including external AIEC revealed that the gene sul1 encoding for sulphonamide resistance was more frequent in AIEC strains than non-AIEC strains (34.6% vs. 9.5%, p = 0.030). AMR in AIEC is a matter of concern regarding the putative implication of the pathotype in CD. The high proportion of AIEC resistant to ?-lactams warrants caution about the risk there may be in the use of these antimicrobials in AIEC-colonized CD patients.
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