Virulence gene profiles and molecular genetic characteristics of diarrheagenic <Emphasis Type="Italic">Escherichia coli</Emphasis> from a hospital in western China

Background

Diarrheagenic Escherichia coli (DEC) is one of the most important etiological agents of diarrheal diseases. In this study we investigated the prevalence, virulence gene profiles, antimicrobial resistance, and molecular genetic characteristics of DEC at a hospital in western China.

Methods

A total of 110 Escherichia coli clinical isolates were collected from the First Affiliated Hospital of Chengdu Medical College from 2015 to 2016. Microbiological methods, PCR, antimicrobial susceptibility test, pulsed-field gel electrophoresis and multilocus sequence typing were used in this study.

Results

Molecular analysis of six DEC pathotype marker genes showed that 13 of the 110 E. coli isolates (11.82%) were DEC including nine (8.18%) diffusely adherent Escherichia coli (DAEC) and four (3.64%) enteroaggregative Escherichia coli (EAEC). The adherence genes fimC and fimH were present in all DAEC and EAEC isolates. All nine DAEC isolates harbored the virulence genes fyuA and irp2 and four (44.44%) also carried the hlyA and sat genes. The virulence genes fyuA, irp2, cnf1, hlyA, and sat were found in 100%, 100%, 75%, 50%, and 50% of EAEC isolates, respectively. In addition, all DEC isolates were multidrug resistant and had high frequencies of antimicrobial resistance. Molecular genetic characterization showed that the 13 DEC isolates were divided into 11 pulsed-field gel electrophoresis patterns and 10 sequence types.

Conclusions

To the best of our knowledge, this study provides the first report of DEC, including DAEC and EAEC, in western China. Our analyses identified the virulence genes present in E. coli from a hospital indicating their role in the isolated DEC strains’ pathogenesis. At the same time, the analyses revealed, the antimicrobial resistance pattern of the DEC isolates. Thus, DAEC and EAEC among the DEC strains should be considered a significant risk to humans in western China due to their evolved pathogenicity and antimicrobial resistance pattern.

     

No evidence of the Shiga toxin-producing E. coli O104:H4 outbreak strain or enteroaggregative E. coli (EAEC) found in cattle faeces in northern Germany, the hotspot of the 2011 HUS outbreak area

Background

Ruminants, in particular bovines, are the primary reservoir of Shiga toxin-producing E. coli (STEC), but whole genome analyses of the current German ESBL-producing O104:H4 outbreak strain of sequence type (ST) 678 showed this strain to be highly similar to enteroaggregative E. coli (EAEC). Strains of the EAEC pathotype are basically adapted to the human host. To clarify whether in contrast to this paradigm, the O104:H4 outbreak strain and/or EAEC may also be able to colonize ruminants, we screened a total of 2.000 colonies from faecal samples of 100 cattle from 34 different farms - all located in the HUS outbreak region of Northern Germany - for genes associated with the O104:H4 HUS outbreak strain (stx2, terD, rfb _O104, fliC _H4), STEC (stx1, stx2, escV), EAEC (pAA, aggR, astA), and ESBL-production (bla _CTX-M, bla _TEM, bla _SHV).

Results

The faecal samples contained neither the HUS outbreak strain nor any EAEC. As the current outbreak strain belongs to ST678 and displays an en-teroaggregative and ESBL-producing phenotype, we additionally screened selected strains for ST678 as well as the aggregative adhesion pattern in HEp-2 cells. However, we were unable to find any strains belonging to ST678 or showing an aggregative adhesion pattern. A high percentage of animals (28%) shed STEC, corroborating previous knowl-edge and thereby proving the validity of our study. One of the STEC also harboured the LEE pathogenicity island. In addition, eleven animals shed ESBL-producing E. coli.

Conclusions

While we are aware of the limitations of our survey, our data support the theory, that, in contrast to other Shiga-toxin producing E. coli, cattle are not the reservoir for the O104:H4 outbreak strain or other EAEC, but that the outbreak strain seems to be adapted to humans or might have yet another reservoir, raising new questions about the epidemiology of STEC O104:H4.     

Effects of indole on drug resistance and virulence of Salmonella enterica serovar Typhimurium revealed by genome-wide analyses

Background

Many Gram-positive and Gram-negative bacteria produce large quantities of indole as an intercellular signal in microbial communities. Indole demonstrated to affect gene expression in Escherichia coli as an intra-species signaling molecule. In contrast to E. coli, Salmonella does not produce indole because it does not harbor tnaA, which encodes the enzyme responsible for tryptophan metabolism. Our previous study demonstrated that E. coli-conditioned medium and indole induce expression of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium for inter-species communication; however, the global effect of indole on genes in Salmonella remains unknown.

Results

To understand the complete picture of genes regulated by indole, we performed DNA microarray analysis of genes in the S. enterica serovar Typhimurium strain ATCC 14028s affected by indole. Predicted Salmonella phenotypes affected by indole based on the microarray data were also examined in this study. Indole induced expression of genes related to efflux-mediated multidrug resistance, including ramA and acrAB, and repressed those related to host cell invasion encoded in the Salmonella pathogenicity island 1, and flagella production. Reduction of invasive activity and motility of Salmonella by indole was also observed phenotypically.

Conclusion

Our results suggest that indole is an important signaling molecule for inter-species communication to control drug resistance and virulence of S. enterica.     

长治地区腹泻患者致泻性大肠杆菌的检测与分析

目的 了解山西省长治地区感染性腹泻患者致泻性大肠杆菌分离情况及菌株特征。方法 收集腹泻患者粪便,EC肉汤增菌后,采用针对致泻性大肠杆菌7个毒力基因eaeA、aggR、ipaH、stx1、stx2、lt、stIb及16S rRNA基因rrs的多重PCR初筛后,阳性者作致泻性大肠杆菌分离,再对分离菌株行生化鉴定、毒力基因检测及血清群测定。结果 170份标本中分离到致泻性大肠杆菌20株,阳性率为12%。其中EPEC 11株,均为非典型EPEC,EAEC 7株,ETEC 2株。结论 长治地区致泻性大肠杆菌感染以5岁以下儿童为主,除EPEC外,EAEC占有很大比例;对致泻性大肠杆菌的检测及判断有赖于血清群与毒力基因检测的分子生物学方法相结合。     

Molecular characterization of diarrheagenic Escherichia coli from Libya

Diarrheagenic Escherichia coli (DEC) are important enteric pathogens that cause a wide variety of gastrointestinal diseases, particularly in children. Escherichia coli isolates cultured from 243 diarrheal stool samples obtained from Libyan children and 50 water samples were screened by polymerase chain reaction (PCR) for genes characteristic of enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enterohemorrhagic E. coli (EHEC), and enteroinvasive E. coli (EIEC). The DEC were detected in 21 (8.6%) children with diarrhea; 10 (4.1%) cases were identified as EAEC, 3 (1.2%) as EPEC, and 8 (3.3%) were ETEC; EHEC, and EIEC were not detected. All DEC were grouped phylogenetically by PCR with the majority (> 70%) identified as phylogenetic groups A and B1. The EAEC isolates were also tested for eight genes associated with virulence using PCR. Multi-virulence (≥ 3 virulence factors) was found in 50% of EAEC isolates. Isolated EAEC possessed different virulence traits and belonged to different phylogenetic groups indicating their heterogeneity.     

Diarrheagenic enteroaggregative Escherichia coli causing urinary tract infection and bacteremia leading to sepsis

We report a case of a 55-year-old immunocompromised female who presented to the emergency department with severe diarrhea and vomiting following travel to the Philippines. Stool bacteriology revealed a mixed infection involving an enteropathogenic Escherichia coli and two distinct strains of enteroaggregative Escherichia coli (EAEC). During hospitalization, urine and blood culture tested positive for one of the diarrheagenic EAEC strains, necessitating urinary catheterization, intensive care, and antimicrobial treatment with trimethoprim–sulfamethoxazole, followed by meropenem. Although known to occasionally cause urinary tract infections, EAEC have not been previously associated with sepsis. Our report highlights the potential of EAEC to cause severe extraintestinal infections.     

Shiga toxin 2a and Enteroaggregative Escherichia coli – a deadly combination

In 2011, a Shiga toxin (Stx) type 2a-producing enteroaggregative E. coli (EAEC) strain of serotype O104:H4 caused a large lethal outbreak in Northern Europe. Until recently, the pathogenic mechanisms explaining the high virulence of the strain have remained unclear. Our laboratories have shown that EAEC genes encoded on the pAA virulence plasmid, particularly the AggR-regulated AAF/I fimbriae, enhance inflammation and enable the outbreak strain to both adhere to epithelial cells and translocate Stx2a across the intestinal epithelium, possibly explaining the high incidence of the life threatening post-diarrheal sequelae of hemolytic uremic syndrome. Epidemiologic evidence supports a model of EAEC pathogenesis comprising the concerted action of multiple virulence factors along with induction of inflammation. Here, we suggest a model for the pathogenesis of the O104:H4 outbreak strain that includes contributions from EAEC alone, but incorporating additional injury induced by Stx2a.     

IS3 profiling identifies the enterohaemorrhagic Escherichia coli O-island 62 in a distinct enteroaggregative E. coli lineage

Background

Enteroaggregative Escherichia coli (EAEC) are important diarrhoeal pathogens that are defined by a HEp-2 adherence assay performed in specialist laboratories. Multilocus sequence typing (MLST) has revealed that aggregative adherence is convergent, providing an explanation for why not all EAEC hybridize with the plasmid-derived probe for this category, designated CVD432. Some EAEC lineages are globally disseminated or more closely associated with disease.

Results

To identify genetic loci conserved within significant EAEC lineages, but absent from non-EAEC, IS3-based PCR profiles were generated for 22 well-characterised EAEC strains. Six bands that were conserved among, or missing from, specific EAEC lineages were cloned and sequenced. One band corresponded to the aggR gene, a plasmid-encoded regulator that has been used as a diagnostic target but predominantly detects EAEC bearing the plasmid already marked by CVD432. The sequence from a second band was homologous to an open-reading frame within the cryptic enterohaemorrhagic E. coli (EHEC) O157 genomic island, designated O-island 62. Screening of an additional 46 EAEC strains revealed that the EHEC O-island 62 was only present in those EAEC strains belonging to the ECOR phylogenetic group D, largely comprised of sequence type (ST) complexes 31, 38 and 394.

Conclusions

The EAEC 042 gene orf1600, which lies within the EAEC equivalent of O-island 62 island, can be used as a marker for EAEC strains belonging to the ECOR phylogenetic group D. The discovery of EHEC O-island 62 in EAEC validates the genetic profiling approach for identifying conserved loci among phylogenetically related strains.     

Etiology of acute diarrhea in children and adults in Tunis, Tunisia, with emphasis on diarrheagenic Escherichia coli: prevalence, phenotyping, and molecular epidemiology

A total of 271 stool specimens were collected from children (diarrheagenic, n = 115 and control, n = 54) and adults (diarrheagenic, n = 73 and control, n = 29) from Tunis, Tunisia, and processed to detect bacterial enteropathogens, parasites, and viruses. Diarrheagenic Escherichia coli (DEC) were identified by their virulence genes (polymerase chain reaction) and adherence patterns (tissue culture assays). The most frequently isolated enteric pathogens from diarrheagenic children were enterotoxigenic E. coli (ETEC, 32.3%), enteroaggregative E. coli (EAEC, 11.3%), enteroinvasive E. coli (EIEC, (11.3%), adenovirus (10.4%), enterohemorrhagic E. coli (EHEC, 10.4%), and Salmonella spp. (9.5%). For children in the control group, ETEC (37%), EAEC (15%), EHEC (11.1%), and typical enteropathogenic E. coli (EPEC, 11.1%) were the most common enteric pathogens. In adults in the diarrheagenic group, Salmonella spp. (34.2%), ETEC (12.3%), adenovirus (7%), and Shigella spp. (4%) were the most common enteric pathogens. In adults in the control group, ETEC (31%) was the most common enteric pathogen. Multiple pathogens were recovered from 22% of the diarrheagenic children and 7% of the diarrheagenic adults. Escherichia coli strains showed high resistance rates to tetracycline, streptomycin, and beta-lactams. The most frequent combinations were ETEC-rotavirus and ETEC-adenovirus. Pulsed-field gel electrophoresis for DEC indicated a large number of DEC clones (five major clones) persistent in the community reservoir for a considerable period of time that caused diarrhea in the population. This suggests the confluence of small epidemics by clonally related DEC strains circulating in this region.     

Diarrheagenic Escherichia coli in Human Immunodeficiency Virus (HIV) Pediatric Patients in Lima,Perú

We conducted a prospective study in three hospitals in Lima in human immunodeficiency virus (HIV) children to determine the frequency of diarrheagenic Escherichia coli. Five E. coli colonies/patients were studied by a multiplex real-time polymerase chain reaction to identify the six currently recognized groups of diarrhea-associated E. coli. We have analyzed 70 HIV-associated diarrheal and 70 control samples from HIV-infected children without diarrhea. Among the diarrheal episodes 19% were persistent, 3% dysenteric, and 33% were associated with moderate or severe dehydration. The diarrheagenic E. coli were the most commonly isolated pathogens in diarrhea (19%) and control samples (26%) (P = 0.42), including enteroaggregative (6% versus 10%), enteropathogenic (6% versus 10%), and enterotoxigenic E. coli (4% versus 3%), respectively. The HIV-infected children with diarrhea had the worse age-related immunosuppression, higher viral loads, and were on highly active antiretroviral treatment (HAART) less often than HIV-infected children without diarrhea. Diarrheagenic E. coli were highly resistant to ampicillin (74%) and cotrimoxazole (70%).     

Antimicrobial resistances do not affect colonization parameters of intestinal E. coli in a small piglet group

Background

Although antimicrobial resistance and persistence of resistant bacteria in humans and animals are major health concerns worldwide, the impact of antimicrobial resistance on bacterial intestinal colonization in healthy domestic animals has only been rarely studied. We carried out a retrospective analysis of the antimicrobial susceptibility status and the presence of resistance genes in intestinal commensal E. coli clones from clinically healthy pigs from one production unit with particular focus on effects of pheno- and/or genotypic resistance on different nominal and numerical intestinal colonization parameters. In addition, we compared the occurrence of antimicrobial resistance phenotypes and genotypes with the occurrence of virulence associated genes typical for extraintestinal pathogenic E. coli.

Results

In general, up to 72.1% of all E. coli clones were resistant to ampicillin, chloramphenicol, kanamycin, streptomycin, sulfamethoxazole or tetracycline with a variety of different resistance genes involved. There was no significant correlation between one of the nominal or numerical colonization parameters and the absence or presence of antimicrobial resistance properties or resistance genes. However, there were several statistically significant associations between the occurrence of single resistance genes and single virulence associated genes.

Conclusion

The demonstrated resistance to the tested antibiotics might not play a dominant role for an intestinal colonization success in pigs in the absence of antimicrobial drugs, or cross-selection of other colonization factors e.g. virulence associated genes might compensate "the cost of antibiotic resistance". Nevertheless, resistant strains are not outcompeted by susceptible bacteria in the porcine intestine.

Trial Registration

The study was approved by the local animal welfare committee of the "Landesamt für Arbeitsschutz, Gesundheitsschutz und technische Sicherheit" Berlin, Germany (No. G0037/02).     

High Frequency of Diarrheagenic Escherichia coli in Human Immunodeficiency Virus (HIV) Patients with and without Diarrhea in Lima,Perú

Diarrhea is still a prevalent health issue in HIV patients. Our objective was to characterize the different diarrheagenic E. coli (DEC) groups in stools from adult HIV patients. Cross sectional study: We enrolled HIV-positive and -negative patients with and without diarrhea from a tertiary-care center of Lima, Peru. Clinical data was recorded and a stool sample per patient was cultured. Multiplex PCR was used to detect different DECs. One hundred eighty-four participants were enrolled. The frequency of having at least one DEC was more common in HIV-positive than HIV-negative patients with diarrhea (42% versus 20%, P < 0.05). The enterotoxigenic E. coli (ETEC) was the most common DEC in patients with diarrhea, 13% in HIV patients. The diffusely adherent E. coli (DAEC) was only present in HIV positive patients with diarrhea (10.1%). Different types of DEC are frequent in stools from HIV-positive patients.Since the highly active anti-retroviral treatment (HAART) was introduced for acquired immunodeficiency syndrome (AIDS), the incidence of opportunistic infections has decreased and new pathogens, such as diarrheagenic Escherichia coli (DEC) groups,¹ are now associated with diarrhea in human immunodeficiency virus (HIV) patients. Because antibiotic therapy may be successful in cases where pathogenic bacteria are identified, studies focusing on bacterial diarrhea in AIDS patients are needed. The DECs have been classified into six groups based on specific genes that determine their virulence factors: enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), Shiga toxin producing E. coli (STEC), enteroagregative E. coli (EAEC), enteropathogen E. coli (EPEC), and diffusely adherent E. coli (DAEC).² The role of different DECs in causing diarrhea in HIV-infected people in Latin American countries has not been adequately addressed because most studies have not examined for all currently recognized groups of DECs. Our objective was to characterize the different DECs in stools from adult HIV patients in Lima, Perú.     

Shiga toxin 2a and Enteroaggregative Escherichia coli – a deadly combination

In 2011, a Shiga toxin (Stx) type 2a-producing enteroaggregative E. coli (EAEC) strain of serotype O104:H4 caused a large lethal outbreak in Northern Europe. Until recently, the pathogenic mechanisms explaining the high virulence of the strain have remained unclear. Our laboratories have shown that EAEC genes encoded on the pAA virulence plasmid, particularly the AggR-regulated AAF/I fimbriae, enhance inflammation and enable the outbreak strain to both adhere to epithelial cells and translocate Stx2a across the intestinal epithelium, possibly explaining the high incidence of the life threatening post-diarrheal sequelae of hemolytic uremic syndrome. Epidemiologic evidence supports a model of EAEC pathogenesis comprising the concerted action of multiple virulence factors along with induction of inflammation. Here, we suggest a model for the pathogenesis of the O104:H4 outbreak strain that includes contributions from EAEC alone, but incorporating additional injury induced by Stx2a.     

Effects of sub-minimum inhibitory concentrations of ciprofloxacin on biofilm formation and virulence factors of Escherichia coli

Objective

To evaluate the influence of sub-minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) on biofilm formation and virulence factors of Escherichia coli clinical isolates.

A one-year prospective study on the antibiotic resistance of E. coli strains isolated in urinary specimens of children hospitalized at the University Pediatric Medical Center in Novi Sad, Serbia

Purpose

Urinary tract infections (UTIs), the most common serious bacterial infections in children, are frequently caused by Escherichia coli. The purpose of this study was to investigate E. coli resistance/multidrug resistance to antibiotics most frequently used for UTIs.

Methods

Children 0–18 years of age, hospitalized at the University Pediatric Hospital in Novi Sad, Serbia, were included in a 1-year observational prospective study. The microbiological analysis was performed using the standard Kirby–Bauer disk diffusion method. The results were analyzed using WHONET 5.4 software.

Results

E. coli was isolated from 61.7 % of positive urine specimens. In general, higher average E. coli antibiotic resistance was found in infants and toddlers compared to children and adolescents (33.4 vs. 25.0 %) (p < 0.0001). Furthermore, it was observed that the average resistance to all the tested antibiotics was higher in boys than in girls (37.0 vs. 25.1 %) (p < 0.0001). E. coli was highly susceptible to piperacillin/tazobactam (>93.1 %), amikacin (86.3 %), quinolones (>75.0 %), and penems (>96.6 %). The prevalence of multiresistant E. coli strains was significantly higher in infants and toddlers (72.3 vs. 36.8 %) (p < 0.0001).

Conclusions

E. coli, a common cause of UTIs in children admitted to pediatric hospitals, is highly resistant/multidrug-resistant to commonly used antibiotics. Higher average resistance is found in infants and toddlers than in children and adolescents, as well as in boys compared to girls. These findings are important for the regional empiric therapy of UTIs and call for actions to decrease E. coli antibiotic resistance.     

Risk factors for non-Escherichia coli community-acquired bacteriuria

Purpose

Urinary tract infection (UTI) is one of the most common bacterial infections, with Escherichia coli causing up to 80 % of community-acquired bacteriuria (CA-Bu). The epidemiology and pathogenesis of E. coli have been intensively studied, yet, less is known about risk factors for CA-Bu due to other uropathogens. The purpose of this study was to clarify the latest knowledge.

Methods

A clinical epidemiological study among adult ambulatory patients was conducted. During November 2009, all urine cultures sent to our Microbiology Laboratory were evaluated, including demographic characteristics of the patients, underlying diseases and antibiotic treatment. Data were analysed by the SPSS statistical package.

Results

During the study period, 4,653 cultures were sent for evaluation. Of the 1,047 (22.5 %) that were positive, 838 were included in the study; 82.5 % were from females. E. coli was the most common pathogen, comprising 58.6 % of all positive cultures. By multivariate analysis, five independent risk factors were associated with non-E. coli CA-Bu: presence of foreign body in the urinary tract [odds ratio (OR) 5.8], nitrite urine test negative (OR 3.2), male gender (OR 2.5), normal erythrocyte count in urine test (OR 1.5) and recurrent UTI in the past year (OR 1.5).

Conclusions

For adult outpatients presenting with CA-Bu, five independent factors suggesting the involvement of uropathogens other than E. coli were identified. These should be taken into consideration when empiric antibiotic treatment is prescribed.     

Quorum sensing in the probiotic bacterium Escherichia coli Nissle 1917 (Mutaflor) – evidence that furanosyl borate diester (AI-2) is influencing the cytokine expression in the DSS colitis mouse model

Background

??Quorum sensing?? (QS) is the phenomenon which allows single bacterial cells to measure the concentration of bacterial signal molecules. Two principle different QS systems are known, the Autoinducer 1 system (AI-1) for the intraspecies communication using different Acyl-homoserine lactones (AHL) and AI-2 for the interspecies communication. Aim of this study was to investigate QS of Escherichia coli Nissle 1917 (Mutaflor).

Results

While E. coli Nissle is producing AI-2 in a density dependent manner, no AI-1 was produced. To study the effect of AI-2 in the DSS (dextran sulphate sodium) induced mouse model of acute colitis, we silenced the corresponding gene luxS by intron insertion. The mutant bacterium E. coli Nissle::luxS was equally effective in colonizing the colon and the mutation turned out to be 100% stable during the course of the experiment. Isolating RNA from the colon mucosa and performing semiquantitative RT PCR, we were able to show that the expression of the pro-inflammatory cytokine IFN-y was suppressed in mice being infected with the E. coli Nissle wild type. Mice infected with the E. coli Nissle::luxS mutant showed a suppressed expression of IL-10 compared to uninfected mice, while the expression of the pro-inflammatory cytokines IL-6 and TNF-?? was higher in these mice. The expression of mBD-1 was suppressed in mice being infected with the mutant in comparison to the mice not infected or infected with the wild type. No differences were seen in the histological examination of the colon sections in the different groups of mice.

Conclusions

E. coli Nissle is producing AI-2 molecules, which are influencing the expression of cytokines in the mucosa of the colon in the DSS mice. However, if QS has a direct influence on the probiotic properties of E. coli Nissle remains to be elucidated.     

Frequency and virulence properties of diarrheagenic Escherichia coli in children with diarrhea in Gabon

To investigate the presence of diarrheagenic Escherichia coli in Lambaréné, Gabon, 150 children with diarrhea were screened for enteroaggregative E. coli (EAEC), enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enterohemorrhagic E. coli (EHEC), and enteroinvasive E. coli (EIEC) using polymerase chain reaction and an HEp-2 cell culture techniques. Isolates of EAEC were detected in 57 children, two thirds of them between six months and two years of age, and isolates of ETEC were detected in seven patients. Isolates of EPEC, EHEC, and EIEC were not present in this population. Among the EAEC, the pCVD432 plasmid, a heat stable (ST)-like (ST-like) enterotoxin (EAST), and a plasmid-encoded heat-labile toxin (PET) were detected in 19, 34, and 42 cases, respectively. Detection of pCVD432, EAST, and PET were significantly associated with EAEC identified by the HEp-2 cell assay. Although detected only in 16 patients, the presence of the fimbriae AAF I (aagA) and AAF II (aafA) were more likely to occur in EAEC than in non-EAEC (odds ratio [OR] = 4.1, 95% confidence interval [CI] = 0.5-38.6, and OR = 2.3, 95% CI = 1.0-5.3, respectively). The EAEC isolates exhibited decreased susceptibility for ampicillin, tetracycline, and trimethoprim.     

Bloodstream infection due to extended-spectrum beta-lactamase (ESBL)-positive K. pneumoniae and E. coli: an analysis of the disease burden in a large cohort

Purpose

The burden of extended-spectrum beta-lactamase (ESBL)-positive Enterobacteriaceae (ESBL-E) is growing worldwide. We aimed to determine the financial disease burden attributable to ESBL-positive species in cases of bloodstream infection (BSI) due to K. pneumoniae and E. coli.

Methods

We conducted a cohort study on patients with BSI due to K. pneumoniae or E. coli between 2008 and 2011 in our institution. Data were collected on true hospital costs, length of stay (LOS), basic demographic parameters, underlying diseases as Charlson comorbidity index (CCI) and ESBL positivity of the pathogens. Multivariable regression analysis on hospital costs and length of stay was performed.

Results

Overall we found 1,851 consecutive cases of ESBL-E BSI, 352 (19.0 %) cases of K. pneumoniae BSI and 1,499 (81.0 %) cases of E. coli BSI. Sixty-six of E. coli BSI (18.8 %) and 178 of K. pneumoniae BSI (11.9 %) cases were due to ESBL-positive isolates, respectively (p = 0.001). 830 (44.8 %) cases were hospital-onset, 215 (61.1 %) of the K. pneumoniae and 615 (41.0 %) of the E. coli cases (p < 0.001). In-hospital mortality was overall 19.8, 25.0 % in K. pneumoniae cases and 18.5 % in E. coli cases (p = 0.006). Increased hospital costs and length of stay were significantly associated to BSI with ESBL-positive K. pneumoniae.

Conclusion

In contrast to BSI due to ESBL-positive E. coli, cases of ESBL-positive K. pneumoniae BSI were associated with significantly increased costs and length of stay. Infection prevention measures should differentiate between both pathogens.