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PubMed1990

[Analysis of plasmid profile of antibiotic-resistant Enterobacteriaceae circulating in hospitals].

Certain pheno- and genotype properties of S. typhimurium and some other representatives of Enterobacteriaceae resistant to antimicrobial drugs were studied. The strains were isolated from children with salmonellosis within 4 months when an infection hospital was subjected to microbiological observation. It was shown that by their antibiotic resistance, phagovars and molecular weights of the plasmid DNas, the strains S. typhimurium were similar to those isolated during hospital infections. The conjugative plasmids responsible for antibiotic resistance in some strains did not differ in their molecular weights and antibiotic resistance markers. The strains S. typhimurium similar in their pheno- and genotype properties were isolated only from 2 patients which allowed one to consider it possible that the patients were infected by the strains of common genesis. Analysis of nonpathogenic representatives of Enterobacteriaceae isolated from the patients along with the S. typhimurium strains confirmed the fact that the patients were infected with the same pathogenic strain.

Anti-Bacterial Agents↗

PubMed1984

[Polyresistant Enterobacteriaceae strains and their plasmids in a hospital. Medical and theoretical aspects].

The properties and origin of multiple resistant strains of Enterobacteriaceae found in the intestine and nasopharynx of infants admitted to the hospital for premature infants were studied. The strains of E. coli of different serovars isolated at various periods contained similar conjugative R plasmids with a molecular weight of 80 Md belonging to the O incompatibility group controlling resistance to kanamycin and physically independent small plasmids controlling resistance to ampicillin (7 Md) and streptomycin-sulfanilamides (4 Md). Multiple drug resistance in the strains of K. pneumoniae was controlled by single large (100-120 Md) plasmid cointegrates with 6-8 resistance markers. Such cointegrates consisted of several potentially independent plasmids, sometimes dividing on transformation of plasmid DNA of the recipient strains of E. coli K12. The small plasmids controlling resistance to ampicillin and streptomycin-sulfanilamides similar to the respective plasmids of E. coli were the constant components of the plasmids cointegrates. The multiple drug resistance in the above strains was combined with high capacity for colonization in premature infants. The medical staff and mothers were the sources of bacterial strains with single plasmids controlling definite types of resistance. It is suggested that the multiple resistant strains of Enterobacteriaceae are formed in hospital as a result of accumulation of the plasmids or plasmid markers and selection. One of the conditions for successive acquisition of new plasmid markers by definite bacterial strains was their high capacity for colonization in patients, which provided constant contacts and genetic exchange of such strains with a wide range of immigrant strains during colonization in the newly admitted patients.

Cross Infection↗

PubMed2024

Investigation of in vitro susceptibility and resistance mechanisms to amikacin among diverse carbapenemase-producing Enterobacteriaceae.

OBJECTIVE: This study aims to assess the in vitro drug susceptibility of various Carbapenemase-Producing Enterobacteriaceae (CPE) genotypes and elucidate the underlying mechanisms of amikacin resistance. METHODS: A total of 72 unique CPE strains were collected from the Second Hospital of Jiaxing between 2019 and 2022, including 51 strains of Klebsiella pneumoniae, 11 strains of Escherichia coli, 6 strains of Enterobacter cloacae, 2 strains of Klebsiella aerogenes, 1 strain of Citrobacter freundii, and 1strain of Citrobacter werkmanii. Among these strains, 24 carried blaKPC gene, 20 carried blaNDM gene, 23 carried blaOXA-48-like gene, and 5 carried both blaKPC and blaNDM. We measured the in vitro activity of amikacin and other common antibiotics. Strains carrying blaOXA-48-like gene were selected for whole genome sequencing (WGS) via next-generation sequencing to identify genes related to antimicrobial resistance (AMR) and virulence factor (VF). RESULTS: Out of the 72 CPE strains tested, 41.7% exhibited resistance to amikacin. The drug resistance rates for K. pneumoniae, E. coli, and Enterobacter spp. were 51.0%, 27.3%, and 10.0%, respectively. The majority of the CPE strains (> 90%) displayed resistance to cephalosporins and carbapenems, while most of them were sensitive to polymyxin B and tigecycline (97.2% and 94.4%). The amikacin resistance rate was 100% for strains carrying blaOXA-48, 20.8% for those with blaKPC, 5.0% for those with blaNDM, and 20.0% for those with both blaKPC and blaNDM. These differences were statistically significant (P < 0.05). Through sequencing, we detected aminoglycoside resistance genes rmtF and aac(6')-Ib, VF genes iucABCD and rmpA2 in OXA-48-producing multidrug resistance and highly virulent strains. These genes were located on a IncFIB- and IncHI1B-type plasmid, respectively. Both plasmids were highly homologous to the plasmid from OXA-232 strains in Zhejiang province and Shanghai province. Integration of these resistance genes into the IncFIB plasmid, facilitated by the IS6 and/or Tn3 transposons, resulted in OXA232-producing K. pneumoniae with amikacin resistance. CONCLUSION: This study identified significant amikacin resistance in CPE strains, particularly in those carrying the blaOXA-48 gene. Resistance genes rmtF and aac(6')-Ib were identified on plasmids. These results highlight the need for careful monitoring of amikacin resistance.

Amikacin↗

PubMed1979

The effect of trimethoprim-sulphonamide, trimethoprim and sulphonamide on the occurrence of resistant enterobacteriaceae in human intestinal flora.

After the administration of various antimicrobial agents for chemotherapeutic purposes a general change in the intestinal flora of the patient is often observed. In contrast, the combination trimethoprim-sulphonamide causes in most cases a strong selective decrease in the number of Enterobacteriaceae organisms for treatment periods as long as four to 12 weeks. The results correspond to clinical experience with trimethoprim-sulphonamide therapy in urinary tract infection where reinfections with resistant organisms are the exception.

Adult↗

PubMed1986

Effect of changing selection pressures on trimethoprim resistance in Enterobacteriaceae.

The incidence of trimethoprim resistance was correlated with changes in prescription behaviour in the Nottingham area from 1978-1985. The prevalence of trimethoprim resistance among Enterobacteriaceae isolated from patients with urinary tract infection rose from 5% to 15% of total strains examined. Strains resistant to trimethoprim but susceptible to sulfamethoxazole appeared from 1980 onward and represented 35% of the total trimethoprim-resistant strains examined in 1985. Co-trimoxazole (trimethoprim + sulfamethoxazole) has been generally available for prescription in the United Kingdom since 1969, whereas trimethoprim alone was released in October 1979. By 1983, prescriptions in the form of trimethoprim alone accounted for approximately 50% (in hospitals) and 15% (in the community) of total trimethoprim usage in the Nottingham area. Although the introduction of trimethoprim alone seems to have had only a minor effect on overall resistance levels, it has greatly increased the proportion of trimethoprim-resistant strains which are susceptible to sulfamethoxazole. This was particularly evident in strains of Proteus spp., in which 52% of the total trimethoprim-resistant strains were sulfamethoxazole-susceptible in 1985.

Drug Combinations↗

PubMed1998

Gentamicin resistance in clinical strains of Enterobacteriaceae associated with reduced gentamicin uptake.

Seven strains of Enterobacteriaceae resistant to gentamicin obtained as representatives of the predominant resistance profiles in the clinical laboratories of Rafeidia and Al-Watani Hospitals in Nablus (Palestine) were included. Five strains showed a broad aminoglycoside resistance profile but contained no evidence of gentamicin acetylation, adenylation, or phosphorylation. Gentamicin uptake in two tested strains was significantly reduced, compared to that of gentamicin-sensitive E. coli (MIC, 0.5 microgram/mL). These strains are likely resistant due to a relative reduction of the amount of gentamicin and other aminoglycosides entering the bacterial cell. Two strains showed evidence of adenyltransferase ANT(2")-I activity.

Anti-Bacterial Agents↗

PubMed2005

Extended-spectrum beta-lactamase-conferring transferable resistance to different antimicrobial agents in Enterobacteriaceae isolated from bloodstream infections.

Twenty (18.5%) out of 108 clinical isolates of the family Enterobacteriaceae responsible for bloodstream infection were extended-spectrum beta-lactamase (ESBL)-positive in two screening tests, the double disk synergy test and the Oxoid Combination Disk method. Eleven out of the 20 ESBL-positive isolates transferred oxyimino-beta-lactam resistance to E. coli K12 C600 recipient strain with a frequency of 10(-8) - 10(-1) per donor cell. PCR analysis revealed that the majority of the transconjugants (9 of 11) express CTX-M-type beta-lactamases. Donor strains and their transconjugants displayed susceptibility patterns typical of ESBL producers. They were resistant to oxyimino-beta-lactams but susceptible to clavulanic acid and carbapenems. Resistances to aminoglycosides, tetracycline and mercuric chloride were, in some cases, co-transferred with oxyimino-beta-lactam resistance, suggesting that various resistance determinants were carried by the same conjugative plasmids.

Anti-Bacterial Agents↗

PubMed2004

Antibiotic resistance rates and phenotypes among isolates of Enterobacteriaceae in French extra-hospital practice.

Antibiotic resistance among members of the family Enterobacteriaceae was prospectively surveyed by eight French private laboratories over a 5-month period in 1999. A total of 2,599 consecutive and nonduplicate strains were collected, mainly (60.9%) from patients in the community. Most strains (82.9%) derived from urine. Escherichia coli was the predominant (73.9%) organism isolated. The overall rates of antibiotic resistance were as follows: amoxicillin, 53.4%; amoxicillin-clavulanic acid, 27.3%; ticarcillin, 44.2%; piperacillin-tazobactam, 3.2%; cephalothin, 29.2%; cefuroxime, 14.7%; cefoxitin, 11.5%; ceftazidime, 3.6%; cefotaxime, 2.8%; cefepime, 0.3%; imipenem, 0.1%; gentamicin (G), 3.8%; tobramycin (T), 5.0%; netilmicin (Nt), 3.7%; amikacin (A), 0.7%; nalidixic acid, 14.3%; ofloxacin, 10.4%; cotrimoxazole, 21.1%; nitrofurantoin, 12.7%; fosfomycin, 5.2%; tetracycline, 50.1%; and colistin, 12.5%. Beta-lactam resistance phenotypes essentially comprised penicillinase production (33.9%), overexpression of chromosomal cephalosporinase (4.6%), and synthesis of inhibitor-resistant TEM/OXA enzymes (1.5%) or extended-spectrum beta-lactamases (1.5%). Aminoglycoside resistance phenotypes consisted of GTNt (93 strains), TNtA (68 strains), GTNtA (14 strains), T (4 strains), GT (3 strains), G (1 strain), and reduced uptake/permeability (3 strains). Most of the nalidixic acid-resistant strains were resistant to ofloxacin (72.8%). Antibiotic resistance rates and phenotypes varied widely according to the bacterial group and the source of the strains. Significantly higher rates were observed in private healthcare centers than in the community, due to a higher proportion of both resistant species and resistant strains. However, multidrug-resistant isolates, including five extended-spectrum beta-lactamase-producing strains, were also recovered from the community.

Ambulatory Care↗

PubMed2005

Risk factors for colonization with third-generation cephalosporin-resistant enterobacteriaceae.

BACKGROUND AND METHOD: Colonization and infections caused by Enterobacteriaceae resistant to third-generation cephalosporins (CRE) have been observed with increasing frequency in intensive care unit (ICU) patients. In contrast to outbreak investigations, information about risk factors for colonization in an endemic situation are rare. We studied risk factors for colonization with CRE in a case control study including 1,706 patients, admitted to any of the 15 ICUs of Heidelberg University Hospitals. RESULTS: 163 patients carried CRE with Enterobacter spp. representing the predominant species. Independent risk factors for CRE carriage in the multivariate logistic regression analysis were an age of under 2.5 years (OR 4.034), an indwelling central venous catheter (CVC) for more than 3 days (OR 2.640), treatment with second- or third generation cephalosporin for longer than 3 days (OR 2.260) and any antibiotic therapy before admission to the ICU. CONCLUSION: Apart from the well-recognized risk factor previous antibiotic treatment, the risk factors age and presence of a CVC might suggest that bacterial overgrowth of the gut either due to an increased susceptibility in younger age or as a consequence of parenteral nutrition is a relevant mechanism for acquiring carriage of CRE in a non-outbreak situation.

Adolescent↗

PubMed1993

The use of colonization rate and epidemic index as tools to illustrate the epidemiology of faecal Enterobacteriaceae strains in Swedish neonatal wards.

The epidemiology of faecal Gram-negative bacteria was studied in 953 infants from 22 neonatal special care wards in Swedish hospitals. Two complementary methods to measure presumed nosocomial transmission of bacterial strains were used: the prevalence rate of major (M) phenotypes (strains that had colonized at least 10% of the infants in a particular ward) and the epidemic index (Ei) (which measures the probability of isolating identical strains from different infants in a ward). About 1500 strains of the most common species (Klebsiella spp., Escherichia coli and Enterobacter cloacae) were typed by the Phene Plate (PhP) biochemical fingerprinting system, and selected Klebsiella isolates were also typed by K antigen serotyping. Klebsiella spp. showed a high propensity to spread (median Ei 0.034, max 0.234), whereas E. coli (median Ei 0.006, max 0.140) and E. cloacae (median Ei 0.0, max 0.012) were more seldom involved in outbreaks. High total Eis in the wards were correlated with high cephalosporin usage (Rs = -0.56, P < 0.05). A total of about 600 biochemical phenotypes of Enterobacteriaceae strains were isolated from the 953 infants. Most of these were found in only one or a few infants, but 24 M phenotypes belonging to Klebsiella spp. (N = 19), E. coli (N = 4) and E. cloacae (N = 1) had colonized altogether 239 (25%) infants. Klebsiella M phenotypes similar or identical to each other and carrying K antigen 55 were isolated from 108 (11%) infants in eight wards, and were thus responsible for 45% of the M phenotype carrier rate in all studied infants. It is suggested that they represent a clone of Klebsiella with a high ability to multiply and spread in hospital environments.

Colony Count, Microbial↗

PubMed2004

Dissemination of CTX-M type beta-lactamases in Enterobacteriaceae isolates in the People's Republic of China.

Previously there have been a number of reports of extended spectrum beta-lactamase (ESBL) producing isolates of the family Enterobacteriaceae in Asia. We first reported the occurrence of bla(CTX-M) in Guangzhou, China, subsequently there have been reports of bla(CTX-M) from a number of other south Asian countries. Initial surveillance study data suggested that bla(CTX-M) might be widely distributed in China. This study examines the type of bla(CTX-M) occurring in other major population centres in China. Initial disk diffusion method susceptibility testing (NCCLS) selected ESBL producing Escherichia coli and Klebsiella pneumoniae isolates from Beijing and near Wuhan, PRC. After screening in both China and the UK, 13 isolates producing CTX-M ESBLs were identified and studied, 11 also produced TEM-1, and 4 also produced SHV-1. Sequence analysis of the bla(CTX-M) containing isolates revealed these isolates contained two different bla(CTX-M), three with bla(CTX-M-3) and 10 with bla(CTX-M-14). After comparison with other previously published studies in the English language, we conclude that the most prevalent bla(CTX-M) so far reported in Asia are bla(CTX-M-14) and bla(CTX-M-3).

Anti-Bacterial Agents↗

PubMed2004

Antimicrobial susceptibility of clinical isolates of Enterobacteriaceae producing complex beta-lactamase patterns including extended-spectrum enzymes.

The antimicrobial susceptibility of 103 clinical isolates of Enterobacteriaceae to 11 antibiotics, was investigated, using a conventional inoculum size (5 x 10(5) CFU) and a higher inoculum size (5 x 10(8) CFU). All the isolates produced complex beta-lactamase patterns, including an extended-spectrum beta-lactamase (ESBL) of the TEM- or SHV-type plus other enzymes (a TEM-type or an SHV-type non-ESBL and/or a class C enzyme). The following repertoire of ESBLs was produced by the isolates: TEM-15, TEM-19, TEM-26, TEM-52, TEM-72, TEM-87, TEM-92, SHV-2a, SHV-5 and SHV-12, as assessed by sequencing. Production of the other enzymes was showed by analytical isoelectric focusing. Overall, meropenem was the most active agent and less influenced by inoculum size, while other beta-lactams showed a lower activity and a significant inoculum size effect. In conclusion, from its in vitro performance, meropenem could be considered as the last resource drug against strains producing complex beta-lactamase patterns including an ESBL.

Anti-Bacterial Agents↗

PubMed2004

Determining incidence of extended spectrum beta-lactamase producing Enterobacteriaceae, vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus in 38 centres from 17 countries: the PEARLS study 2001-2002.

The PEARLS study prospectively monitored selected nosocomial pathogens from 38 centres in 13 European, three Middle Eastern countries and South Africa during 2001-2002. Extended spectrum beta-lactamase (ESBL) production rates among Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp. were 5.4% (142/2609), 18.2% (401/2,206) and 8.8% (204/2,328), respectively, for all study sites. The overall ESBL production rate for the combined Enterobacteriaceae was 10.5% (747/7,143), highest in Egypt, 38.5%, and Greece, 27.4%, and lowest in The Netherlands, 2.0%, and Germany, 2.6%. IEF, PCR and DNA sequencing determined 10.7% false positives among Enterobacter spp. when using NCCLS guidelines to screen for ESBL production. The prevalence of nosocomial methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium was 32.4% (294/908) and 8.7% (83/949), respectively. PEARLS provides baseline data against which prospective changes in resistant determinants and outcomes can be measured in this ongoing study.

Anti-Bacterial Agents↗

PubMed2004

Beta-lactam susceptibilities and prevalence of ESBL-producing isolates among more than 5000 European Enterobacteriaceae isolates.

In vitro susceptibility to 15 beta-lactam antibiotics was evaluated using Enterobacteriaceae isolated during the SENTRY Antimicrobial Surveillance Program. Piperacillin/tazobactam was the most active penicillin against Escherichia coli, Proteus mirabilis, Klebsiella oxytoca and Klebsiella pneumoniae (94.9%, 98.3%, 87.4% and 82.9% of isolates susceptible). Of the cephalosporins, cefepime was most effective against Escherichia coli, Proteus mirabilis and Enterobacter cloacae (99.2%, 96.3% and 95.2% of isolates susceptible, respectively) and cefoxitin against Klebsiella oxytoca and Klebsiella pneumoniae (98.6% and 95.6% of isolates susceptible). Carbapenems had excellent activity (> or =99.5% of all isolates). ESBL-production was confirmed with the ESBL-Etest and disk diffusion test in 1.3% of Escherichia coli isolates, 18.4% of Klebsiella pneumoniae, 12.6% of Klebsiella oxytoca and 5.3% of Proteus mirabilis isolates.

Aztreonam↗

PubMed2026

Multidimensional prophage profiling of carbapenem-resistant Enterobacteriaceae in Thailand: a nationwide, multicentre, genomic study.

BACKGROUND: Prophages influence bacterial fitness, resistance, and evolution, yet their epidemiology remains poorly understood in carbapenem-resistant Enterobacteriaceae (CRE). In this nationwide study in Thailand, we aimed to describe prophage repertoires in clinical CRE isolates and to explore their potential relevance for molecular epidemiology. METHODS: We performed a nationwide, retrospective, genomic analysis of all CRE clinical isolates collected through our previous national surveillance study involving 11 hospitals in 11 provinces in Thailand between March 25, 2012, and Jul 21, 2017. Whole-genome sequencing data from 747 CRE isolates were analysed. Intact prophages were identified using PHAge Search Tool Enhanced Release (PHASTER) and clustered by nucleotide sequence similarity. Prophage profiles were compared across multilocus sequence types, carbapenemase genotypes, specimens, geography, and patient demographics (age and sex). FINDINGS: Of the included 747 CRE isolates, 170 (23%) were Escherichia coli and 577 (77%) were Klebsiella pneumoniae. 220 (29%) of 747 strains had been isolated from female patients and 264 (35%) from male patients; metadata on patient sex were missing for 263 (35%) isolates. The median patient age was 63 years (IQR 50-72). 71 (10%) of isolates were from blood, 283 (38%) from sputum, 284 (38%) from urine, and 109 (15%) from other specimens. 374 distinct prophage clusters were identified, with significantly more prophages per genome in K pneumoniae (mean 3·01 [SD 1·55]) than in E coli (1·64 [1·46]; p<0·0001). Prophage repertoires largely mirrored bacterial multilocus sequence types. However, even within the highly clonal K pneumoniae sequence type 16 lineage, discrete prophage variation was identified, with common profiles observed in geographically dispersed patients. Respiratory K pneumoniae frequently carried a mosaic prophage with environmental signatures and a type VI secretion system, whereas blood-derived E coli harboured a prophage with immune-modulating genes. Distinct prophage clusters were observed across clinical specimens, age groups, carbapenemase genotype, and geographical region. Strains coharbouring blaNDM-1 plus blaOXA-232 (114 [15%] of 747) had the highest prophage loads. INTERPRETATION: The prophage content was shaped by the bacterial lineage, ecological niche, and temporal dynamics, providing an additional layer of epidemiological resolution beyond conventional genome typing. Integrating prophage profiling into molecular surveillance frameworks could help to identify transmission events, improve infectious source attribution, and enhance infection control strategies. FUNDING: Japan Agency for Medical Research and Development.

Female↗

PubMed2001

[Spread of Enterobacteriaceae producing broad-spectrum beta-lactamase and the development of their incidence over a 16-month period in a university hospital center].

Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLE) constitute with methicillin-resistant Staphylococcus aureus the main multiresistant bacteria recovered in French hospitals. Our objectives were to evaluate these ESBLE diffusion in our teaching hospital and to follow their incidence during a 16-month period, whereas a control programme (barrier precautions) had been implemented in the beginning of 1999. This study was conducted in a teaching hospital containing 1800 beds, from February 1999 to May 2000. All ESBLE isolated in clinical or screening samples were included. Duplicates (same bacteria in the same patient) were excluded. The detection of the ESBL was performed with the double-disk diffusion test. Incidence densities were determined with their 95% confidence interval (CI95%). Their evolution by four-month period was evaluated with the chi-square test for trend. During the 16-month period, 229 ESBLE were isolated. The incidence was 0.35 per 1000 patient-days (PD) (CI95% = [0.30-0.40]) for the whole hospital. It was 0.47/1000 PD (CI95% = [0.38-0.56]) in medical wards, 0.29/1000 PD (CI95% = [0.20-0.38]) in surgical wards and 1.32/1000 PD (CI95% = [0.90-1.74]) in intensive care units. Enterobacter aerogenes strains represented more than 75% of all ESBLE, whereas Klebsiella pneumoniae stains represented only 8.6%. During the study, the incidence of ESBLE and the proportion of strains acquired in our hospital decreased significantly (p < 0.0001 and p < 0.001 respectively). Indeed, between the first eight-month period and the last one, the incidence of ESBLE acquired in our hospital decreased by 55%, whereas the incidence of imported strains increased slightly. This study shows that the diffusion of ESBLE concerns the entire hospital. The implementation of a control programme of the spread of multiresistant bacteria allowed us to reduce significantly the incidence of ESBLE. This incidence seemed to be stable for several months. The implementation of a policy which restricts antimicrobial use would allow us to complete the the efficacy of barrier precautions.

Academic Medical Centers↗

PubMed2003

Increasing prevalence of antimicrobial resistance among Enterobacteriaceae uropathogens in Dakar, Senegal: a multicenter study.

To assess antibiotic susceptibility among Enterobacteriaceae isolated in urine from outpatients in Dakar, Senegal, a prospective multicenter study involving 3 laboratories had been conducted between June and October 2001. During this period, 300 strains were isolated and susceptibility testing was performed against antibiotics commonly used in treatment of community-acquired urinary tract infections (UTI). E. coli and K. pneumoniae represented 89% of isolates. The overall resistance rates of ampicillin, amoxicillin-clavulanic acid, nalidixic acid, fluoroquinolones and cotrimoxazole were respectively 77.3%, 34.7%, 14.7%, 13.3%, and 55%. In the light of these results, a re-evaluation of first line therapies and prudent use of fluoroquinolones is advised. At the same time a continued surveillance of antimicrobial resistance should be developed in Senegal in order to control the emergence of multidrug resistant strains and to establish a national therapeutic guideline for treatment of UTI.

Adolescent↗

PubMed2000

Genome plasticity in Enterobacteriaceae.

The comparative analysis of multiple representatives of the genomes of particular species are leading us away from a view of bacterial genomes as static, monolithic structures towards the view that they are relatively variable, fluid structures. This plasticity is mainly the result of the rearrangement of genes within the genome and the acquisition of novel genes by horizontal transfer systems, e. g. plasmids, bacteriophages, transposons or gene cassettes. These mechanisms often act in concert thus generating a complex genetic structure. Genomic variations are not a phenomenon at the DNA level alone, they influence the phenotype of a bacterium as well and can render a formerly harmless organism into a hazardous pathogen. This review deals not only with the mechanisms of genome rearrangements and the horizontal transfer of genes in Enterobacteriaceae but also points out that mobile genetic elements themselves are subjected to variation.

Bacteriophages↗