ESBL-producing Enterobacteriaceae Research Articles

Geographic mapping of Enterobacteriaceae with extended-spectrum \u03b2-lactamase (ESBL) phenotype in Pereira, Colombia

BackgroundAntimicrobial resistance is an ecological and multicausal problem. Infections caused by extended-spectrum β-lactamase producing Enterobacteriaceae (ESBL-E) can be acquired and transmitted in the community. Data on community-associated ESBL-E infections/colonizations in Colombia are scarce. Georeferencing tools can be used to study the dynamics of antimicrobial resistance at the community level.MethodsWe conducted a study of geographic mapping using modern tools based on geographic information systems (GIS). Two study centers from the city of Pereira, Colombia were involved. The records of patients who had ESBL-producing Enterobacteriaceae were reviewed. Antimicrobial susceptibility testing and phenotypic detection of ESBL was done according to CLSI standards.ResultsA population of 415 patients with community-acquired infections/colonizations and 77 hospital discharges were obtained. Geographic distribution was established and heat maps were created. Several hotspots were evidenced in some geographical areas of the south-west and north-east of the city. Many of the affected areas were near tertiary hospitals, rivers, and poultry industry areas.ConclusionsThere are foci of antimicrobial resistance at the community level. This was demonstrated in the case of antimicrobial resistance caused by ESBL in a city in Colombia. Causality with tertiary hospitals in the city, some rivers and the poultry industry is proposed as an explanation of the evidenced phenomenon. Geographic mapping tools are useful for monitoring antimicrobial resistance in the community.

Prevalence of Extended-Spectrum β-Lactamases in E. coli of Rats in the Region North East of Gabon.

Antibiotic resistance occurs in the environment by multiplication and the spread of multidrug-resistant bacteria that would be due to an improper and incorrect use of antibiotics in human and veterinary medicine. The aim of this study was to establish the prevalence of E.coli producing Extended-Spectrum beta-Lactamase (ESBL) antibiotics from rats and gregarious animals in a semirural area of Gabon and to evaluate the origin of a resistance distribution in the environment from animal feces. The bacterial culture was carried out, and the identification of E. coli strains on a specific medium and the antibiotic susceptibility tests allowed establishing the prevalence. Characterization of resistance genes was performed by gene amplification after DNA extraction. On 161 feces collected in rats, 32 strains were isolated, and 11 strains of E. coli produced ESBL with a prevalence of 34.37%. Molecular tests showed that CTX-M genes 214 bp were identified in rats. The presence of CTX-M genes could have a human origin. So, the rats can carry ESBL-producing Enterobacteriaceae which poses a risk to human health and pets in this region of Gabon.

The use of eugenol in combination with cefotaxime and ciprofloxacin to combat ESBL-producing quinolone-resistant pathogenic Enterobacteriaceae.

Emergence of extended-spectrum beta-lactamase (ESBL) producing with quinolone-resistant (QR) pathogenic Enterobacteriaceae augmented the need to establish therapeutic options against them. Present study aimed towards determination of synergistic combination of eugenol (EG) with cefotaxime (CTX) and ciprofloxacin (CIP) to combat against this resistance and potentiation of antibacterial drugs by EG against these bacteria. Synergistic interaction between EG and CTX/CIP (FICI: 0·08-0·5) were observed among ESBL-QR bacteria using checkerboard assay. Approximately, 2- to 1024-fold minimum inhibitory concentration value reduction and 17- to 165030-fold dose reduction index strongly suggested synergistic interaction between EG and antibiotics. Cell viability assay showed reduction in log10 CFU per ml from 16·6 to 3·1 at synergistic concentration. Scanning electron microscopy further proved disruptive effect of EG on cell architecture. Eugenol and/or its combination also altered genes' expressions that imparted antibiotic resistance by ~1·6 to ~1226 folds. Reduced doses of antibiotics, bacterial morphological alterations, efflux pump down regulation, porin over expression and beta-lactamase gene inhibition of ESBL-QR bacteria by EG alone or in combination with CTX/CIP might have reversed antibiotic resistance profile of ESBL-QR bacteria. This study provided a molecular insight into action of EG and/with CTX and CIP, which might have potentiated antibiotic's activity against ESBL-QR bacteria.

Epidemiology of extended-spectrum β-lactamase-producing Enterobacteriaceae among healthcare students, at the Portuguese Red Cross Health School of Lisbon, Portugal

ObjectiveThe aim of the present study was to prospectively evaluate the prevalence of intestinal carriage by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae among Portuguese students attending a Bachelors’ course in healthcare, and to determine the molecular features of ESBL-producing isolates. MethodsOne-hundred and eleven faecal samples recovered from Portuguese healthcare students were screened for either ESBL-producing, carbapenem-resistant, colistin-resistant or pan-aminoglycoside-resistant Enterobacteriaceae, using respective screening media. All recovered isolates were tested for antimicrobial susceptibility and characterised by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). ResultsA total of 17 ESBL-producing Enterobacteriaceae (16 Escherichia coli and a single Klebsiella pneumoniae) were recovered from 16 students, representing a prevalence of 14.5%. The E. coli isolates were distributed into three sequence types (STs) and seven PFGE types. The most common ESBL identified was CTX-M-1 (n=13; 76%), followed by CTX-M-15 (n=3; 18%) and CTX-M-8 (n=1; 6%). The majority of the strains were resistant to sulfonamides (88%) and fosfomycin (71%). Resistance to aminoglycosides was observed at a low rate, that is 12% for both tobramycin and kanamycin. No colistin-, carbapenem- or pan-aminoglycoside-resistant isolates were recovered. A major clone, ST10-blaCTX-M-1, included 12 E. coli isolates. The blaCTX-M-1 gene was always located on an IncFIA/FIB plasmid type, co-harbouring genes encoding resistance to tetracycline, sulfonamides, trimethoprim–sulfamethoxazole and fosfomycin. ConclusionThe most commonly identified ESBL gene in E. coli was blaCTX-M-1, usually identified among ESBL-producing isolates recovered from animals. A high prevalence of faecal carriage of ESBL-producing E. coli was found among healthy healthcare students, underlying this population as an important reservoir.

Combination of Rifampicin and Colistin against antibiotic resistant Enterobacteriaceae

Antimicrobial resistance is one of the greatest challenges for humanity. Patients, especially, admitted to the intensive care unit have been exposed to higher risk of healthcare associated infections mostly caused by antibiotic resistance since the imprudent use of antibiotics over the years. The discovery and development of new antibiotics are facing difficulties with the continuous evolution of drug resistance in bacteria, and the reduced investment in R&D for antibiotics from pharmaceutical companies. Novel strategies are urgently needed to control this pandemic threat of antibiotic resistance. Antibiotic combination with two or more drugs may be useful in targeting resistant gram-negative bacteria by producing synergistic effect and enhanced bactericidal activates. In this study, we determined the combination of rifampicin and colistin against Extended Spectrum Beta Lactamase (ESBL), carbapenemase producing and colistin resistant Enterobacteriaceae using chequerboard method and time kill curves. We measured the combination effects based on Fractional Inhibitory Concentration index (FICI) and the efficacy of bacterial reduction comparing to that of single antibiotic. Interestingly, we found that the combination of rifampicin and colistin showed synergistic activities against the tested bacteria, indicating FIC index ≤0.5. The time kill curve shows that the two drugs combination exhibits 99% kill whilst the single antibiotic had no activities. Thus, the combination of rifampicin and colistin demonstrated synergistic activity with reduced MIC and the increased rate of killing against both ESBL and carbapenemsase producing and colistin resistant Enterobacteriaceae.

CTX-M group gene distribution of extended spectrum beta-lactamase-producing Enterobacteriaceae at a Japanese Children's hospital

Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae have spread globally as one of the most common multidrug resistant organisms. Although a wide variety of ESBL genes were known in each geographical region, few reports existed on the distribution of ESBL genes in Japanese children. To clarify the distribution of ESBL genes, we investigated the CTX-M type of the ESBL-producing Enterobacteriaceae and patient characteristics among hospital-acquired and community-acquired cases. Total of 253 isolates of ESBL-producing Enterobacteriaceae were recovered from 238 pediatric patients. ESBL-producing Enterobacteriaceae were mostly recovered from children with underlying diseases (76.5%). Ratio of community-acquired and hospital-acquired cases was 58.8% and 41.2%, respectively. Compared to the hospital-acquired cases, community-acquired cases had younger age, fewer underlying diseases, and the dominant detection of Escherichia coli. The most common ESBL-producing Enterobacteriaceae was E. coli (79.8%), followed by Klebsiella pneumoniae (9.1%). CTX-M9 group was the most prevalent CTX-M group gene (63.2%), which was dominantly detected in E. coli (72.7%). This was the largest descriptive study to find CTX-M9 group as the most prevalent ESBL genotype among Enterobacteriaceae isolated from Japanese children in line with adult's epidemiology.

Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial.

Background: The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics of fecal microbiota changes in a sub-cohort of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. Methods: We sequenced fecal DNA obtained from 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding seven donors. Ten treatment-naïve controls from the same trial were included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (V3, V4 and V5). Results: Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). Bifidobacterium species, together with butyrate- and propionate-producing species from Lachnospiraceae and Ruminococcaceae families were significantly enriched in post-FMT microbiota of treated carriers. After FMT, the proportion of Enterobacteriaceae was lower compared to baseline but without statistical significance. Conclusions: Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE.

Association of intestinal colonization of ESBL-producing Enterobacteriaceae in poultry slaughterhouse workers with occupational exposure-A German pilot study.

BackgroundBacteria that have acquired antimicrobial resistance, in particular ESBL-producing Enterobacteriaceae, are an important healthcare concern. Therefore, transmission routes and risk factors are of interest, especially for the carriage of ESBL-producing E. coli. Since there is an enhanced risk for pig slaughterhouse employees to carry ESBL-producing Enterobacteriaceae, associated with animal contact as potential risk factor, the present study investigated the occurrence of ESBL-producing Enterobacteriaceae in poultry slaughterhouse employees. Due to the higher level of resistant Enterobacteriaceae in primary poultry production than in pig production, a higher risk of intestinal colonization of poultry slaughterhouse employees was expected.ResultsESBL-producing Enterobacteriaceae were detected in 5.1% (5 of 99) of the fecal samples of slaughterhouse workers. The species of these isolates was confirmed as E. coli. PCR assays revealed the presence of the genes blaCTX-M-15 (n = 2) and blaSHV-12 (n = 3) in these isolates, partly in combination with the β-lactamase gene blaTEM-135. Participants were divided into two groups according to their occupational exposure and results indicated an increased probability of colonization with ESBL-producing Enterobacteriaceae for the group of ‘higher exposure’ (OR 3.7, exact 95% CI 0.6–23.5; p = 0.4). For intestinal colonization with ESBL-producing Enterobacteriaceae, a prevalence of 10% (3/30) was observed in the group of ‘higher exposure’ versus 2.9% (2/69) in the group of ‘lower exposure’. Employees in working steps such as ‘hanging’ poultry in the process of slaughter and ‘evisceration’ seemed to have a higher risk for intestinal colonization with ESBL-producing Enterobacteriaceae compared to the group of ‘lower exposure’.ConclusionThis study is the first of its kind to collect data on the occupational exposure of slaughterhouse workers to ESBL-producing Enterobacteriaceae in Europe. The results suggested that colonization with ESBL-producing Enterobacteriaceae is associated with occupational exposure in poultry slaughterhouses. However, the presence of ESBL-producing E. coli isolates in only 5.1% (5/99) of the tested employees in poultry slaughterhouses suggests a lower transmission risk than in pig slaughterhouses.

Detection and characterization of ESBL-producing Enterobacteriaceae from the gut of healthy chickens, Gallus gallus domesticus in rural Nepal: Dominance of CTX-M-15-non-ST131 Escherichia coli clones.

The surge in the prevalence of drug-resistant bacteria in poultry is a global concern as it may pose an extended threat to humans and animal health. The present study aimed to investigate the colonization proportion of extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacteriaceae (EPE and CPE, respectively) in the gut of healthy poultry, Gallus gallus domesticus in Kaski district of Western Nepal. Total, 113 pooled rectal swab specimens from 66 private household farms and 47 commercial poultry farms were collected by systematic random sampling from the Kaski district in western Nepal. Out of 113 pooled samples, 19 (28.8%) samples from 66 backyard farms, and 15 (31.9%) from 47 commercial broiler farms were positive for EPE. Of the 38 EPE strains isolated from 34 ESBL positive rectal swabs, 31(81.6%) were identified as Escherichia coli, five as Klebsiella pneumoniae (13.2%), and one each isolate of Enterobacter species and Citrobacter species (2.6%). Based on genotyping, 35/38 examined EPE strains (92.1%) were phylogroup-1 positive, and all these 35 strains (100%) had the CTX-M-15 gene and strains from phylogroup-2, and 9 were of CTX-M-2 and CTX-M-14, respectively. Among 38 ESBL positive isolates, 9 (23.7%) were Ambler class C (Amp C) co-producers, predominant were of DHA, followed by CIT genes. Two (6.5%) E. coli strains of ST131 belonged to clade C, rest 29/31 (93.5%) were non-ST131 E. coli. None of the isolates produced carbapenemase. Twenty isolates (52.6%) were in-vitro biofilm producers. Univariate analysis showed that the odd of ESBL carriage among commercial broilers were 1.160 times (95% CI 0.515, 2.613) higher than organically fed backyard flocks. This is the first study in Nepal, demonstrating the EPE colonization proportion, genotypes, and prevalence of high-risk clone E. coli ST131 among gut flora of healthy poultry. Our data indicated that CTX-M-15 was the most prevalent ESBL enzyme, mainly associated with E. coli belonging to non-ST131clones and the absence of carbapenemases.

The Gut of Healthy Infants in the Community as a Reservoir of ESBL and Carbapenemase-Producing Bacteria

The recent rapid rise of multi-drug resistant Enterobacteriaceae (MDR-E) is threatening the treatment of common infectious diseases. Infections with such strains lead to increased mortality and morbidity. Using a cross-sectional study, we aimed to estimate the prevalence of gut colonization with extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae among healthy infants born in Pakistan, a setting with high incidence of MDR-E infections. Stool samples were collected from 104 healthy infants between the ages of 5 and 7 months. Enterobacteriaceae isolates were screened for resistance against several antimicrobial classes. Presence of ESBL and carbapenemase genes was determined using multiplex PCR. Sequence types were assigned to individual strains by multi-locus sequence typing. Phylogenetic analysis of Escherichia coli was done using the triplex PCR method. Forty-three percent of the infants were positive for ESBL-producing Enterobacteriaceae, the majority of which were E. coli. We identified several different ESBL E. coli sequence types most of which belonged to the phylogenetic group B2 (23%) or D (73%). The widespread colonization of infants in a developing country with ESBL-producing Enterobacteriaceae is concerning. The multiple sequence types and reported non-human sources support that multiple non-epidemic MDR lineages are circulating in Pakistan with healthy infants as a common reservoir.

Oral cephalosporin and β-lactamase inhibitor combinations for ESBL-producing Enterobacteriaceae urinary tract infections.

ESBL-producing Enterobacteriaceae as uropathogens have given rise to a sizeable amount of global morbidity. Community and hospital surveillance studies continue to report increasing proportions of these organisms as causes of urinary tract infection (UTI). Due to limited treatment options and the presence of cross-resistance amongst oral antibiotics of different classes, patients often require IV therapy, thereby increasing healthcare costs and reducing the effectiveness of delivering healthcare. Oral cephalosporin antibiotics are well known for their ability to achieve high urinary concentrations, in addition to achieving clinical success for treatment of uncomplicated UTI with a drug-susceptible pathogen. Novel cephalosporin/β-lactamase inhibitor combinations have been developed and demonstrate good in vitro activity against ESBL-producing isolates. A pooled analysis of in vitro activity of existing oral cephalosporin/clavulanate combinations in ESBL-producing Enterobacteriaceae has shown MIC50s of 0.5-1, 0.125-1 and 0.25 mg/L for cefpodoxime, ceftibuten and cefixime, respectively. A novel cyclic boronic acid β-lactamase inhibitor, QPX7728, was able to produce MIC50 values of 0.5 and ≤0.06 mg/L when paired with cefpodoxime and ceftibuten, respectively. Other novel combinations, cefpodoxime/ETX0282 and ceftibuten/VNRX7145, have also demonstrated excellent activity against ESBL producers. Clinical trials are now awaited.

Prevalence and associated factors for carriage of Enterobacteriaceae producing ESBLs or carbapenemase and methicillin-resistant Staphylococcus aureus in Hong Kong community

ObjectivesWe conducted a cross-sectional study in Hong Kong community to estimate the carriage prevalence, associated factors and genotypes of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E), methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase-producing Enterobacteriaceae (CPE). MethodsSeemingly healthy subjects were asked to provide nasal, handprint and stool samples from March to April 2017. Isolates were characterized by molecular methods. We used multivariable logistic regression models within a generalized estimating equation framework to identify risk factors for ESBL-E carriage. Characteristics of MRSA/CPE carriage were summarized. ResultsThe prevalence of ESBL-E, MRSA and CPE were 52.8% (104/197), 2.5% (5/197) and 0.5% (1/197) respectively. Most ESBL-E isolates were E. coli (85.6%; 113/132). Most ESBL genes belonged to blaCTX−M-G9 (68.9%) and blaTEM (53.0%) types. Self-reported antibiotic consumption (≥2 courses) in the past six months was associated with ESBL-E carriage (adjusted odds ratio: 4.71–5.47). ConclusionsAbundance of ESBL-E in the community are causes of concern, and antibiotic use is associated with its carriage. Presence of MRSA and CPE in community members without clear healthcare exposure hints on a change in their epidemiology. This study establishes a baseline to formulate infection control policies and future studies in combating antimicrobial resistance.

Prevalence of Fecal Carriage of Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae Among School Children in South Sulawesi, Indonesia

Background: Fecal carriage of extended-spectrum β-lactamase (ESBL)-producing bacteria is a potential risk for transmission and infection. Genotypes known to be associated with ESBL-producing Enterobacteriaceae are cefotaximases (CTX-M), temoniera (TEM), and sulfhydryl variable (SHV). Unfortunately, data on ESBL prevalence in Indonesia, especially in South Sulawesi, is still limited, so further research on the community is needed. Objectives: This study aimed to investigate the prevalence of fecal carriage of ESBL-producing Enterobacteriaceae among school children in South Sulawesi, Indonesia. Methods: The research was conducted among school-children in South Sulawesi, Indonesia. Detection of ESBL gene using polymerase chain reaction (PCR) methods. A total of 245 stool samples were collected. Results: The prevalence of fecal carriage of ESBL-producing Enterobacteriaceae among school children was 76.7% (188/245). Genotyping of EBSL-producing Enterobacteriaceae encoding genes using PCR found that TEM genes, 92.6% (174/188), were higher than SHV genes, 38.8% (73/188) and CTX-M genes, 4.3% (8/188). It was also revealed a combination of ESBL-producing genes of Enterobacteriaceae. The most combination genes were found in TEM + SHV genes, including 55 of 188 (29.26%). Conclusions: The presence of ESBL gene careers suggests that antibiotic resistance has spread in the community, which needs to be of concern since it can be an ESBL gene reservoir that can be transmitted to many pathogenic bacteria.

Tigecycline Therapy for Infections Caused by Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Critically Ill Patients.

We aimed to evaluate tigecycline on the clinical effectiveness in treating complicated skin and soft tissue infections (cSSTI), complicated intra-abdominal infections (cIAI), and pneumonia, caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, as data are limited. From three medical centers in Taiwan, we retrospectively studied the cSSTI, cIAI, and/or pneumonia caused by ESBL-producing Enterobacteriaceae. Among the 71 patients, including 39 patients infected with Klebsiella pneumoniae, 30 infected with Escherichia coli and others, the clinical success rate of tigecycline-based therapy was 80–90% for pneumonia and cSSTI caused by E. coli and 50–60% for cIAI caused by K. pneumoniae and E. coli. Microbiological and clinical outcome of pneumonia caused by carbapenem-resistant K. pneumoniae was poor. Univariate Cox analysis showed that dyspnea, SOFA score, septic shock, thrombocytopenia, prolonged prothrombin time, and lesser microbiological eradication were significant factors associated with 30-day mortality after the end of therapy. Cox regression proportional hazards model revealed dyspnea and a SOFA score > 8 to be independently associated with time to death. For ESBL producers, tigecycline showed good effects for cSSTI and pneumonia by E. coli, ordinary for cIAI, but ineffective for pneumonia by K. pneumoniae. Dyspnea and a high SOFA score predict a poor outcome.

<p>Prevalence of Extended-Spectrum Beta-Lactamase-Producing <em>Enterobacteriaceae</em> Causing Bloodstream Infections in Cancer Patients from Southwest of Iran</p>

IntroductionThis study aimed to evaluate the frequency rate of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) causing bloodstream infections (BSIs) in cancer patients referred to one of the major referral hospitals in Ahvaz city, southwest Iran.Materials and MethodsIn this study, 1700 blood cultures were collected from 610 cancer patients suspected to have BSI from October 2016 to August 2017 referred to the Shafa cancer hospital, Ahvaz, southwest of Iran. The blood culture bottles were incubated aerobically at 35–37ºC for 24 hours and then sub-cultured on routine microbiology culture media. The bacterial colonies were identified using standard tests. The antibiotic susceptibility testing was achieved by the disc-diffusion method. The phenotypic detection of ESBLs was carried out by the combination disc-diffusion test (CDDT). Finally, the polymerase chain reaction (PCR) was performed to investigate the presence of blaTEM, blaCTX, blaSHV, and blaPER genes.ResultsThe prevalence of BSI in cancer patients was 16.4% (100/610). Gram-negative rods with rate of 74% (74/100) were the most prevalent bacteria. The frequency of Enterobacteriaceae family was 21% including Escherichia coli (n: 8), Klebsiella pneumoniae (n: 6), Enterobacter spp. (n: 5), Citrobacter freundii (n: 1), and Serratia marcescens (n: 1). All isolates were multidrug-resistant (resistance to three or more antibiotics). The results of CDDT showed that 42.8% (9/21) of Enterobacteriaceae isolates had a positive ESBL test of which 100% (9/9) indicated positive band for at least one of the ESBL genes by PCR method. The blaCTX-M and blaTEM genes were detected in 38% (8/21) and 23.8% (5/21) of isolates, respectively, while the blaSHV and blaPER were not detected in any isolates.ConclusionBased on the results, surveillance, and antibiotic stewardship programs should be implemented for cancer patients to prevent the spread of more ESBL-PE that have limited therapeutically choices.

Gastrointestinal Tract Colonization Rate of Extended-Spectrum Beta-Lactamase- and Carbapenemase-Producing Enterobacteriaceae and Associated Factors Among Hospitalized Patients in Arba Minch General Hospital, Arba Minch, Ethiopia.

BackgroundThe incidence of hospital-acquired enterobacteria that produce extended-spectrum beta-lactamases (ESBLs) is on the rise worldwide. Colonization of gastrointestinal tract by extended-spectrum beta-lactamase Enterobacteriaceae, a prominent causative agent, results in life-threatening infections.ObjectiveTo determine the rate of gastrointestinal colonization by extended-spectrum beta-lactamase- and carbapenemase-producing Enterobacteriaceae and also to elucidate the antibiotic susceptibility profile and associated risk factors among hospitalized patients in Arba Minch General Hospital, Ethiopia.MethodologyA facility-based cross-sectional study was conducted in Arba Minch General Hospital from May 2018 to July 2019. Sociodemographic data and associated factors were collected using a pre-tested-structured questionnaire. Stool specimens were collected using sterile stool cups. Each sample was then inoculated onto MacConkey agar. Bacterial isolates were identified using various biochemical tests. Screening and confirmatory tests for extended-spectrum beta-lactamase- and carbapenemase-producing Enterobacteriaceae were performed using the modified Kirby–Bauer disc diffusion technique. Statistical package for Social Science was used to analyze the data. The P-value ≤0.05 was considered as statistically significant.ResultsA total of 421 hospitalized patients were enrolled in this study of which there were 240 (57%) females. The mean age of the study participants was 28.8 with SD of 15.7. Majority of participants were in the age range of 25–40 years 179 (42.5%). About 146 (34.7%) participants were found to be colonized by extended-spectrum beta-lactamase-producing Enterobacteriaceae. The predominant ESBL-producing isolates were Escherichia coli 62 (42.46%) followed by Klebsiella pneumoniae 60 (41.09%). Six (1.43%) carbapenemase-producing K. pneumoniae were isolated. ESBL-producing Enterobacteriaceae showed higher resistance against tetracycline (91.1%) and cotrimoxazole (93.84%). Colonization of the gastrointestinal tract by ESBL showed statistically significant association with regard to chronic diseases (p<0.001) and the administration of oral antibiotics after admission (p=0.020).ConclusionThe overall colonization rate of the gastrointestinal tract by extended-spectrum beta-lactamase-producing Enterobacteriaceae was prominent. The extended-spectrum beta-lactamase-producing isolates exhibited a higher level of resistance against the commonly used antibiotics which further needs greater attention.

Epidemiology and Prognosis of Intensive Care Unit-Acquired Bloodstream Infection.

.Intensive care unit–acquired bloodstream infections (ICU-BSI) are frequent and are associated with high morbidity and mortality rates. We conducted this study to describe the epidemiology and the prognosis of ICU-BSI in our ICU and to search for factors associated with mortality at 28 days. For this, we retrospectively studied ICU-BSI in the ICU of the Cayenne General Hospital, from January 2013 to June 2019. Intensive care unit–acquired bloodstream infections were diagnosed in 9.5% of admissions (10.3 ICU-BSI/1,000 days). The median delay to the first ICU-BSI was 9 days. The ICU-BSI was primitive in 44% of cases and secondary to ventilator-acquired pneumonia in 25% of cases. The main isolated microorganisms were Enterobacteriaceae in 67.7% of patients. They were extended-spectrum beta-lactamase (ESBL) producers in 27.6% of cases. Initial antibiotic therapy was appropriate in 65.1% of cases. Factors independently associated with ESBL-producing Enterobacteriaceae (ESBL-PE) as the causative microorganism of ICU-BSI were ESBL-PE carriage before ICU-BSI (odds ratio [OR]: 7.273; 95% CI: 2.876–18.392; P < 0.000) and prior exposure to fluoroquinolones (OR: 4.327; 95% CI: 1.120–16.728; P = 0.034). The sensitivity of ESBL-PE carriage to predict ESBL-PE as the causative microorganism of ICU-BSI was 64.9% and specificity was 81.2%. Mortality at 28 days was 20.6% in the general population. Factors independently associated with mortality at day 28 from the occurrence of ICU-BSI were traumatic category of admission (OR: 0.346; 95% CI: 0.134–0.894; P = 0.028) and septic shock on the day of ICU-BSI (OR: 3.317; 95% CI: 1.561–7.050; P = 0.002). Mortality rate was independent of the causative organism.

Low incidence of antibiotic-resistant bacteria in south-east Sweden: An epidemiologic study on 9268 cases of bloodstream infection.

The aim of this study was to investigate the epidemiology of bloodstream infections (BSI) in a Swedish setting, with focus on risk factors for BSI-associated mortality. A 9-year (2008-2016) retrospective cohort study from electronic records of episodes of bacteremia amongst hospitalized patients in the county of Östergötland, Sweden was conducted. Data on episodes of BSI including microorganisms, antibiotic susceptibility, gender, age, hospital admissions, comorbidity, mortality and aggregated antimicrobial consumption (DDD /1,000 inhabitants/day) were collected and analyzed. Multidrug resistance (MDR) was defined as resistance to at least three groups of antibiotics. MDR bacteria and MRSA, ESBL-producing Enterobacteriaceae, vancomycin-resistant enterococci not fulfilling the MDR criteria were all defined as antimicrobial-resistant (AMR) bacteria and included in the statistical analysis of risk factors for mortality. In all, 9,268 cases of BSI were found. The overall 30-day all-cause mortality in the group of patients with BSI was 13%. The incidence of BSI and associated 30-day all-cause mortality per 100,000 hospital admissions increased by 66% and 17% respectively during the nine-year study period. The most common species were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae and Enterococcus faecalis. Independent risk factors for 30-day mortality were age (RR: 1.02 (CI: 1.02-1.03)) and 1, 2 or ≥3 comorbidities RR: 2.06 (CI: 1.68-2.52), 2.79 (CI: 2.27-3.42) and 2.82 (CI: 2.31-3.45) respectively. Almost 3% (n = 245) of all BSIs were caused by AMR bacteria increasing from 12 to 47 per 100,000 hospital admissions 2008-2016 (p = 0.01), but this was not associated with a corresponding increase in mortality risk (RR: 0.89 (CI: 0.81-0.97)). Comorbidity was the predominant risk factor for 30-day all-cause mortality associated with BSI in this study. The burden of AMR was low and not associated with increased mortality. Patients with BSIs caused by AMR bacteria (MDR, MRSA, ESBL and VRE) were younger, had fewer comorbidities, and the 30-day all-cause mortality was lower in this group.

Calculated parenteral initial treatment of bacterial infections: Infections with multi-resistant Gram-negative rods - ESBL producers, carbapenemase-producing Enterobacteriaceae, carbapenem-resistant Acinetobacter baumannii.

This is the sixteenth chapter of the guideline “Calculated initial parenteral treatment of bacterial infections in adults – update 2018” in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience.Infections due to multiresistant Gram-negative rods are challenging. In this chapter recommendations for targeted therapy for infections caused by ESBL-producing Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae and carbapenem-resistant Acinetobacter baumannii are given, based on the limited available evidence.

Prevalence of the carbapenem-heteroresistant phenotype among ESBL-producing Escherichia coli and Klebsiella pneumoniae clinical isolates.

Carbapenem-heteroresistant (cHR) Enterobacteriaceae strains have been reported worldwide; however, the prevalence among clinical ESBL-producing Enterobacteriaceae isolates obtained from patients with repeated hospital admissions remains largely unknown. Heteroresistance was screened by disc diffusion and confirmed by a modified population analysis profiling (PAP) method against ertapenem, imipenem, meropenem and ceftolozane/tazobactam. MIC testing was performed by broth microdilution against carbapenems and a panel of agents with potential activity against ESBL-producing strains. One hundred and seventy-three ESBL-producing meropenem-susceptible Escherichia coli and Klebsiella pneumoniae isolates were selected for testing. A total of 519 bacteria/carbapenem combinations were screened by disc diffusion; 84 combinations were identified as cHR. Modified PAP confirmed 70 bacteria/carbapenem combinations as heteroresistant; most (63%, 44/70) confirmed cHR colonies grew within the ertapenem zone of inhibition, followed by imipenem (30%, 21/70), then meropenem (7%, 5/70). In total, one-third of the unique patient isolates (32%, 55/173) were identified as being heteroresistant to at least one carbapenem; of those patients, 16% (9/55) had a carbapenem-non-susceptible isolate on subsequent visits. Only two cHR isolates screened positive for ceftolozane/tazobactam heteroresistance (1%, 2/173), of which one was confirmed heteroresistant by modified PAP. cHR isolates were more likely to be collected from a non-urinary source (e.g. respiratory) compared with non-cHR isolates (31% versus 19%, P = 0.02). MIC distributions of all tested antibiotic agents did not differ between non-cHR and cHR isolates. Our findings raise concerns for the continued use of carbapenems as first-line therapy for ESBL infections and for the potential selection for strains with full carbapenem resistance.