Third-generation Cephalosporin-resistant Enterobacteriaceae Research Articles

Antibiotic Prescriptions in Critically Ill Patients with Bloodstream Infection Due to ESBL-Producing Enterobacteriaceae: Compliance with the French Guidelines for the Treatment of Infections with Third-Generation Cephalosporin-Resistant Enterobacteriaceae-A Multicentric Retrospective Cohort Study.

National and international guidelines were recently published regarding the treatment of Enterobacteriaceae resistant to third-generation cephalosporins infections. We aimed to assess the implementation of the French guidelines in critically ill patients suffering from extended-spectrum β-lactamase-producing Enterobacteriaceae bloodstream infection (ESBL-E BSI). We conducted a retrospective observational cohort study in the ICU of three French hospitals. Patients treated between 2018 and 2022 for ESBL-E BSI were included. The primary assessment criterion was the proportion of adequate empirical carbapenem prescriptions, defined as prescriptions consistent with the French guidelines. Among the 185 included patients, 175 received an empirical anti-biotherapy within 24 h of ESBL-E BSI onset, with a carbapenem for 100 of them. The proportion of carbapenem prescriptions consistent with the guidelines was 81%. Inconsistent prescriptions were due to a lack of prescriptions of a carbapenem, while it was recommended in 25% of cases. The only factor independently associated with adequate empirical carbapenem prescription was ESBL-E colonization (OR: 107.921 [9.303-1251.910], p = 0.0002). The initial empirical anti-biotherapy was found to be appropriate in 83/98 patients (85%) receiving anti-biotherapy in line with the guidelines and in 56/77 (73%) patients receiving inadequate anti-biotherapy (p = 0.06). Our results illustrate the willingness of intensivists to spare carbapenems. Promoting implementation of the guidelines could improve the proportion of initial appropriate anti-biotherapy in critically ill patients with ESBL-E BSI.

Colonizations and infections due to 3GCR Enterobacteriaceae in a University hospital in Italy

Abstract Background The spread of third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB) is an increasing issue in terms of antimicrobial resistance and infection prevention and control (IPC), especially in the hospital setting. We aimed to investigate the burden of colonizations and infections caused by 3GCREB in an Italian teaching hospital. Methods We performed a retrospective study on cases of 3GCREB isolation from microbiological specimens (from gastrointestinal, urinary, blood, respiratory and cutaneous systems) which were detected over a year period (January-December 2022) at the University Hospital of Verona, Italy. We reviewed the corresponding patients’ charts to retrieve clinical information and classify cases as colonizations vs. infections. Infections counted as hospital-acquired (HAI) when the 3GCREB was detected after the third day following admission, otherwise as community-acquired infection (CAI). Results Of 2,451 3GCREB isolates retrieved, 1,815 (74.1%) were from rectal swabs. The monthly detection trend was consistent throughout the year with a minimum in February (n = 159) and a maximum in August (n = 238); monthly average was 204 isolates. The majority of 3GCREB isolates (n = 1,887; 77%) were classified as colonizations. Of the 564 3GCREB isolates which were classified as infections (23% of total isolates), 305 (54.1%) were HAIs and 259 (45.9%) were CAIs. The highest proportion of HAIs (n = 121; 39.7%) was detected in medical units, followed by intensive care areas (n = 100; 32.8%) and surgical units (n = 84; 27.5%). Conclusions Comparing the percentages of patients with 3GCREB colonization and infection, we conclude the presence of 3GCREB in our hospital to be about 3 times higher than when only patients with 3GCREB infections are considered. This highlights the importance of surveillance to protect fragile patients. IPC training of staff is essential to counter the intra-hospital spread of these pathogens. Key messages • Prevalence of 3GCREB is an increasing healthcare issue in the hospital setting and medical directions should focus on staff IPC training to counter the spread of these pathogens. • Detection of 3GCREB colonizations is crucial to track the spread of multidrug-resistant organisms, identify cases and protect fragile patients.

A prospective multicentre screening study on multidrug-resistant organisms in intensive care units in the Dutch-German cross-border region, 2017 to 2018: the importance of healthcare structures.

BackgroundAntimicrobial resistance poses a risk for healthcare, both in the community and hospitals. The spread of multidrug-resistant organisms (MDROs) occurs mostly on a local and regional level, following movement of patients, but also occurs across national borders.AimThe aim of this observational study was to determine the prevalence of MDROs in a European cross-border region to understand differences and improve infection prevention based on real-time routine data and workflows.MethodsBetween September 2017 and June 2018, 23 hospitals in the Dutch (NL)–German (DE) cross-border region (BR) participated in the study. During 8 consecutive weeks, patients were screened upon admission to intensive care units (ICUs) for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) and rectal carriage of vancomycin-resistant Enterococcus faecium/E. faecalis (VRE), third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) and carbapenem-resistant Enterobacteriaceae (CRE). All samples were processed in the associated laboratories.ResultsA total of 3,365 patients were screened (median age: 68 years (IQR: 57–77); male/female ratio: 59.7/40.3; NL-BR: n = 1,202; DE-BR: n = 2,163). Median screening compliance was 60.4% (NL-BR: 56.9%; DE-BR: 62.9%). MDRO prevalence was higher in DE-BR than in NL-BR, namely 1.7% vs 0.6% for MRSA (p = 0.006), 2.7% vs 0.1% for VRE (p < 0.001) and 6.6% vs 3.6% for 3GCRE (p < 0.001), whereas CRE prevalence was comparable (0.2% in DE-BR vs 0.0% in NL-BR ICUs).ConclusionsThis first prospective multicentre screening study in a European cross-border region shows high heterogenicity in MDRO carriage prevalence in NL-BR and DE-BR ICUs. This indicates that the prevalence is probably influenced by the different healthcare structures.

Prevalence and characterization of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolated from raw vegetables retailed in Southern Thailand.

BackgroundThe increasing prevalence of broad-spectrum ampicillin-resistant and third-generation cephalosporin-resistant Enterobacteriaceae, particularly Escherichia coli and Klebsiella pneumoniae, has become a global concern, with its clinical impacts on both human and veterinary medicine. This study examined the prevalence, antimicrobial susceptibility, and molecular genetic features of extended-spectrum β-lactamase (ESBL)-producing E. coli and K. pneumoniae isolates from 10 types of raw vegetables.MethodsIn total, 305 samples were collected from 9 markets in Nakhon Si Thammarat, Thailand, in 2020.ResultsESBL-producing E. coli and K. pneumoniae isolates were found in 14 of the 305 samples obtained from 7 out of 10 types of vegetables (4.6% of the total). Further, 14 ESBL-producing E. coli (n = 5/14) and K. pneumoniae isolates (n = 9/14) (1.6% and 3.0%, respectively) were highly sensitive to β-lactam/carbapenem antibiotics (imipenem, 100%). ESBL-producing E. coli (n = 4) and K. pneumoniae isolates (n = 8) were also sensitive to non-β-lactam aminoglycosides (amikacin, 80.00% and 88.89%, respectively). ESBL producers were most resistant to β-lactam antibiotics, including ampicillin (85.71%) and the cephalosporins cefotaxime and ceftazidime (64.29%). The most frequently detected gene in ESBL-producing E. coli and K. pneumoniae was blaSHV. However, two ESBL-producing E. coli isolates also carried three other ESBL-encoding variants, blaTEM, blaCTX-M1, blaGES and blaTEM, blaSHV, blaCTX-M9, which may be due to their association with food chains and humans.DiscussionIndeed, our results suggest that raw vegetables are an important source of ESBL-resistant E. coli and K. pneumoniae, which are potentially transmittable to humans via raw vegetable intake.

Mortality associated with third generation cephalosporin-resistance in Enterobacteriaceae infections: a multicenter cohort study in Southern China

ABSTRACT Background: Emerging third-generation cephalosporin-resistant Enterobacteriaceae (3GCR-EB) pose global healthcare concern. This study assessed the in-hospital mortality attributed to 3GCR-EB. Methods: The study cohort comprised inpatients with community-onset or healthcare-associated infection caused by Enterobacteriaceae in three tertiary-care public hospitals in 2017. In-hospital mortality was compared between 3GCR-EB infected patients and third-generation cephalosporin-susceptible Enterobacteriaceae (3GCS-EB) infected patients using competing risk survival models. Results: Of 2,343 study patients (median age 60 years; 45.2% male), 1,481 (63.2%) had 3GCS-EB and 862 (36.8%) 3GCR-EB infection. 494 (57.0%) 3GCR-EB isolates were co-resistant to fluoroquinolones and 15 (1.7%) to carbapenems. In-hospital mortality was similar in 3GCS-EB and 3GCR-EB infections (2.4% vs. 2.8%; p = 0.601). No increase in the hazard of in-hospital mortality was detected for 3GCR-EB compared to 3GCS-EB infection (sub-distribution hazard ratio [HR] 0.80; 95%CI, 0.41–1.55) adjusting for patient age, sex, intensive care admission, origin of infection and site of infection. Analysis of cause-specific hazards showed that 3GCR-EB infections significantly decreased the daily rate of hospital discharge (cause-specific HR = 0.84; 95%CI, 0.76–0.92) leading to lengthier hospitalizations. Conclusion: 3GCR-EB infection per se was not associated with increased in-hospital mortality in this study, but placed significant healthcare burden by increasing the length of hospitalization.

Third-generation cephalosporin resistant Enterobacteriaceae in neonates and young infants: impact and outcome

Objective Third-generation cephalosporins resistant Enterobacteriaceae (3GCR-EB) are a major threat in severely ill neonates hospitalized in Neonatal Intensive Care Units. Still, the particular impact of 3GCR-EB on outcomes in the wide neonatal population is not well-appreciated. We aimed to study the impact of 3GCR-EB on the length of hospital stay and mortality of a general population of neonates and young infants. Study design This was a retrospective cohort study of neonates and young infants born in eight Israeli hospitals between 2009 and 2013, with a culture taken within three months after birth that tested positive for Enterobacteriaceae (EB). Data for this study were taken from centralized electronic health records included inpatient, outpatient, socio-demographic, administrative and laboratory information. The main outcomes were length of stay and mortality. The main explanatory variable was an isolation of 3GCR-EB in any bacterial culture taken from a neonate or young infant. Results Cultures were taken for 31,921 neonates and young infants; 2647 (8.3%) tested positive for EB and 290 (11%) tested positive for 3GCR-EB. Length of stay for those who tested positive was 2.8 times longer (95%CI: 2.70–2.91, p ˂ .001) than patients who tested positive for 3GC-susceptible EB. 3GCR-EB were also associated with increased mortality (OR: 12.06, 95%CI: 4.92–32.29). Conclusions Neonates with third-generation cephalosporins resistant Enterobacteriaceae had extended hospitalization and increased mortality, which was mostly significant in normal gestational weight newborns.

Risks and burdens of third-generation cephalosporin resistant Enterobacteriaceae in neonatal sepsis.

Third-generation cephalosporin resistant Enterobacteriaceae (TCRE) is a global concern especially in neonatal sepsis. We performed a secondary data analysis in a Thai neonatal intensive care unit to identify the risk factors for acquisition of TCRE sepsis and mortality of Enterobacteriaceae sepsis between 1991 and 2017. Multivariate logistic and Cox proportional regression were used for analysis. Numbers of neonates with TCRE and nonTCRE sepsis were 100 and 41 patients, respectively. Medians (interquartile ranges) of gestational age, birthweight, onset of sepsis and total hospital stay of neonates with Enterobacteriaceae sepsis were 32 (28, 38) weeks, 1670 (1025, 2750) grams, 11 (6, 25) days and 41 (22, 74) days, respectively. Univariate and multivariate analysis, neonates with TCRE sepsis were more likely to have birth asphyxia (adjusted odds ratio [aOR] = 2.6; 95% confidence interval [CI] 1.1-6.0; p = 0.02) and history of aminoglycoside exposure (aOR = 2.9; 95% CI 1.3- 6.7; p = 0.01). In-hospital case fatality rate from Enterobacteriaceae sepsis was 26% (36/141). In Cox regression, neonates with TCRE sepsis was not an independent risk of non-survivors, but septic shock (adjusted hazard ratio = 9.9; 95% CI 5.0-19.7, p < 0.001) increased 30-day mortality in the final model. Asphyxia and previous aminoglycoside consumption were risks of acquisition for neonatal TCRE sepsis while the burden was not a significant difference. Infection prevention and control must be strictly implemented in high multidrug-resistant area.

Effectiveness and safety of an institutional aminoglycoside-based regimen as empirical treatment of patients with pyelonephritis.

To determine clinical outcomes associated with aminoglycosides versus other antimicrobial agents as empirical treatment of hospitalized patients with pyelonephritis. An institutional programme promoting aminoglycosides as empirical treatment of pyelonephritis was implemented in 2016. We reviewed the hospital records of patients with pyelonephritis from January 2017 to April 2019. The primary outcome was death within 30 days of index culture. Initial treatment with aminoglycoside-based regimens was compared with non-aminoglycoside antibiotics. Propensity score matching was performed to adjust for between-group differences in baseline covariates. The study cohort included 2026 patients, 715 treated with aminoglycosides and 1311 treated with non-aminoglycoside drugs (ceftriaxone, n = 774; piperacillin/tazobactam, n = 179; carbapenems, n = 161; and fluoroquinolones, n = 133); 589 patients (29%) had bloodstream infections. Treatment with aminoglycosides was associated with a higher likelihood of in vitro activity against clinical isolates (OR = 2.0; P < 0.001). Death at 30 days occurred in 55 (7.6%) versus 145 (11%) patients treated with aminoglycosides and non-aminoglycoside drugs, respectively (adjusted HR = 0.78; P = 0.013). Aminoglycosides were either superior or similar to comparator drugs in all patient subgroups, stratified according to age, glomerular filtration rate, bacteraemia, haemodynamic shock and infection with third-generation cephalosporin-resistant Enterobacteriaceae. The incidence of acute kidney injury was similar for aminoglycosides and comparators (2.5% versus 2.9%, respectively; P = 0.6). Within the context of an institutional programme, initial empirical treatment of pyelonephritis with aminoglycosides was associated with higher rates of in vitro activity and lower overall mortality compared with non-aminoglycoside drugs, without excess nephrotoxicity.

Risk factors for third-generation cephalosporin resistant Enterobacteriaceae in gestational urine cultures: A retrospective cohort study based on centralized electronic health records.

Third-generation-cephalosporin resistant Enterobacteriaceae (3GCR-EB) carriage in pregnant women poses challenges for infection control and therapeutic decisions. The factors associated with multidrug resistant Enterobacteriaceae carriage in the gestational period are not well documented. The aim of our study was to identify risk factors associated with 3GCR-EB isolation in gestational urine cultures. The study was designed as retrospective cohort based on centralized electronic health records database. Women delivered in Clalit Health Services hospitals in Israel in 2009-2013 and provided urine culture(s) during pregnancy were included. Multivariable analysis using the Generalized Estimating Equations model was used to assess risk factors for 3GCR-EB isolation in gestational urine cultures. The study included 15,282 pregnant women with urine cultures yielding Enterobacteriaceae (EB). The proportion of 3GCR-EB in EB isolates was 3.9% (n = 603). The following risk factors were associated with 3GCR-EB isolation: multiple hospital admissions during the year before delivery (OR,1.47;95% CI,1.21-1.79), assisted fertilization procedure (OR,1.53; 95% CI,1.12-2.10), Arab ethnicity (OR,1.22; 95% CI,1.03-1.45), multiple antibiotic courses (OR,1.76; 95% CI,1.29-2.40), specifically, cephalosporins (OR,1.56; 95% CI,1.26-1.95), fluoroquinolones (OR,1.34; 95% CI,1.04-1.74), or nitrofurantoin (OR,1.29; 95% CI,1.02-1.64). The risk factors identified by this study for 3GCR-EB in gestation, can be easily generalized for pregnant women in the Israeli population. Moreover, these risk factors, other than ethnicity, are applicable to pregnant women worldwide. The information of previous antibiotic treatments, hospitalization in the last year and assisted fertilization procedure can be easily accessed and used for appropriate infection control practices and antimicrobial therapy.

European intensive care physicians\u2019 experience of infections due to antibiotic-resistant bacteria

BackgroundAntimicrobial resistance (AMR) compromises the treatment of patients with serious infections in intensive care units (ICUs), and intensive care physicians are increasingly facing patients with bacterial infections with limited or no adequate therapeutic options. A survey was conducted to assess the intensive care physicians’ perception of the AMR situation in the European Union/European Economic Area (EU/EEA).MethodsBetween May and July 2017, physicians working in European ICUs were invited to complete an online questionnaire hosted by the European Society of Intensive Care Medicine. The survey included 20 questions on hospital and ICU characteristics, frequency of infections with multidrug-resistant (MDR) bacteria and relevance of AMR in the respondent’s ICU, management of antimicrobial treatment as well as the use of last-line antibiotics in the six months preceding the survey. For the analysis of regional differences, EU/EEA countries were grouped into the four sub-regions of Eastern, Northern, Southern and Western Europe.ResultsOverall, 1062 responses from four European sub-regions were analysed. Infections with MDR bacteria in their ICU were rated as a major problem by 257 (24.2%), moderate problem by 360 (33.9%) and minor problem by 391 (36.8%) respondents. Third-generation cephalosporin-resistant Enterobacteriaceae were the most frequently encountered MDR bacteria followed by, in order of decreasing frequency, meticillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and vancomycin-resistant enterococci. Perception of the relevance of the AMR problem and the frequency of specific MDR bacteria varied by European sub-region. Bacteria resistant to all or almost all available antibiotics were encountered by 132 (12.4%) respondents. Many physicians reported not having access to specific last-line antibiotics.ConclusionsThe percentage of European ICU physicians perceiving AMR as a substantial problem in their ICU is high with variation by sub-region in line with epidemiological studies. The reports of bacteria resistant to almost all available antibiotics and the limited availability of last-line antibiotics in ICUs in the EU/EEA are of concern.

Prevalence and outcome of bloodstream infections due to third-generation cephalosporin-resistant Enterobacteriaceae in sub-Saharan Africa: a systematic review.

BackgroundThe prevalence of bacterial bloodstream infections (BSIs) in sub-Saharan Africa (sSA) is high and antimicrobial resistance is likely to increase mortality from these infections. Third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae are of particular concern, given the widespread reliance on ceftriaxone for management of sepsis in Africa.ObjectivesReviewing studies from sSA, we aimed to describe the prevalence of 3GC resistance in Escherichia coli, Klebsiella and Salmonella BSIs and the in-hospital mortality from 3GC-R BSIs.MethodsWe systematically reviewed studies reporting 3GC susceptibility testing of E. coli, Klebsiella and Salmonella BSI. We searched PubMed and Scopus from January 1990 to September 2019 for primary data reporting 3GC susceptibility testing of Enterobacteriaceae associated with BSI in sSA and studies reporting mortality from 3GC-R BSI. 3GC-R was defined as phenotypic resistance to ceftriaxone, cefotaxime or ceftazidime. Outcomes were reported as median prevalence of 3GC resistance for each pathogen.ResultsWe identified 40 articles, including 7 reporting mortality. Median prevalence of 3GC resistance in E. coli was 18.4% (IQR 10.5 to 35.2) from 20 studies and in Klebsiella spp. was 54.4% (IQR 24.3 to 81.2) from 28 studies. Amongst non-typhoidal salmonellae, 3GC resistance was 1.9% (IQR 0 to 6.1) from 12 studies. A pooled mortality estimate was prohibited by heterogeneity.ConclusionsLevels of 3GC resistance amongst bloodstream Enterobacteriaceae in sSA are high, yet the mortality burden is unknown. The lack of clinical outcome data from drug-resistant infections in Africa represents a major knowledge gap and future work must link laboratory surveillance to clinical data.

Selective culture enrichment and sequencing of feces to enhance detection of antimicrobial resistance genes in third-generation cephalosporin resistant Enterobacteriaceae.

Metagenomic sequencing of fecal DNA can usefully characterise an individual's intestinal resistome but is limited by its inability to detect important pathogens that may be present at low abundance, such as carbapenemase or extended-spectrum beta-lactamase producing Enterobacteriaceae. Here we aimed to develop a hybrid protocol to improve detection of resistance genes in Enterobacteriaceae by using a short period of culture enrichment prior to sequencing of DNA extracted directly from the enriched sample. Volunteer feces were spiked with carbapenemase-producing Enterobacteriaceae and incubated in selective broth culture for 6 hours before sequencing. Different DNA extraction methods were compared, including a plasmid extraction protocol to increase the detection of plasmid-associated resistance genes. Although enrichment prior to sequencing increased the detection of carbapenemase genes, the differing growth characteristics of the spike organisms precluded accurate quantification of their concentration prior to culture. Plasmid extraction increased detection of resistance genes present on plasmids, but the effects were heterogeneous and dependent on plasmid size. Our results demonstrate methods of improving the limit of detection of selected resistance mechanisms in a fecal resistome assay, but they also highlight the difficulties in using these techniques for accurate quantification and should inform future efforts to achieve this goal.

Development of a bedside tool to predict the probability of drug-resistant pathogens among hospitalized adult patients with gram-negative infections

BackgroundWe developed a clinical bedside tool to simultaneously estimate the probabilities of third-generation cephalosporin-resistant Enterobacteriaceae (3GC-R), carbapenem-resistant Enterobacteriaceae (CRE), and multidrug-resistant Pseudomonas aeruginosa (MDRP) among hospitalized adult patients with Gram-negative infections.MethodsData were obtained from a retrospective observational study of the Premier Hospital that included hospitalized adult patients with a complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), hospital-acquired/ventilator-associated pneumonia (HAP/VAP), or bloodstream infection (BSI) due to Gram-negative bacteria between 2011 and 2015. Risk factors for 3GC-R, CRE, and MDRP were ascertained by multivariate logistic regression, and separate models were developed for patients with community-acquired versus hospital-acquired infections for each resistance phenotype (N = 6). Models were converted to a singular user-friendly interface to estimate the probabilities of a patient having an infection due to 3GC-R, CRE, or MDRP when ≥ 1 risk factor was present.ResultsOverall, 124,068 patients contributed to the dataset. Percentages of patients admitted for cUTI, cIAI, HAP/VAP, and BSI were 61.6, 4.6, 16.5, and 26.4%, respectively (some patients contributed > 1 infection type). Resistant infection rates were 1.90% for CRE, 12.09% for 3GC-R, and 3.91% for MDRP. A greater percentage of the resistant infections were community-acquired relative to hospital-acquired (CRE, 1.30% vs 0.62% of 1.90%; 3GC-R, 9.27% vs 3.42% of 12.09%; MDRP, 2.39% vs 1.59% of 3.91%). The most important predictors of having an 3GC-R, CRE or MDRP infection were prior number of antibiotics; infection site; infection during the previous 3 months; and hospital prevalence of 3GC-R, CRE, or MDRP. To enable application of the six predictive multivariate logistic regression models to real-world clinical practice, we developed a user-friendly interface that estimates the risk of 3GC-R, CRE, and MDRP simultaneously in a given patient with a Gram-negative infection based on their risk (Additional file 1).ConclusionsWe developed a clinical prediction tool to estimate the probabilities of 3GC-R, CRE, and MDRP among hospitalized adult patients with confirmed community- and hospital-acquired Gram-negative infections. Our predictive model has been implemented as a user-friendly bedside tool for use by clinicians/healthcare professionals to predict the probability of resistant infections in individual patients, to guide early appropriate therapy.

Assessment of the In Vitro Activities of Ceftolozane/Tazobactam and Ceftazidime/Avibactam in a Collection of Beta-Lactam-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Clinical Isolates at Montpellier University Hospital, France.

Objective: To assess in vitro ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) activity in beta-lactam-resistant Enterobacteriaceae and Pseudomonas aeruginosa clinical isolates from major carbapenem-using Departments at Montpellier University Hospital, France. Materials and Methods: We tested third-generation cephalosporin-resistant Enterobacteriaceae (by production of extended spectrum β-lactamase or other mechanisms, mainly AmpC beta-lactamases) and ceftazidime- and/or carbapenem-resistant P. aeruginosa strains isolated from clinical samples of patients hospitalized from January 2017 to May 2017 and August 2016 to July 2017, respectively. We also included all OXA-48 beta-lactamase-producing Enterobacteriaceae strains isolated in the whole hospital from October 2015 to May 2017. We used the 2017 European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines for minimal inhibitory concentration interpretation. Results: Among the 62 cephalosporin-resistant Enterobacteriaceae strains, 60 (97%) were susceptible to CZA and 34 (65%) to C/T. The two CZA-resistant Klebsiella pneumoniae isolates produced (i) NDM-carbapenemase and extended-spectrum beta-lactamase (ESBL) and (ii) ESBL CTXM-15 and OXA-1 associated with impermeability. Moreover, 31 of the 42 P. aeruginosa strains (74%) were susceptible to CZA and 37 (88%) to C/T. Finally, 26/27 (96%) of OXA-48 beta-lactamase-producing Enterobacteriaceae were susceptible to CZA and 8/27 (30%) to C/T. Conclusions: At our hospital, CZA and C/T offer a carbapenem-sparing alternative for resistant gram-negative pathogens and could be a salvage therapy for carbapenem-resistant pathogens.

A novel disk-based detection method with superior sensitivity for β-lactamase production in third-generation cephalosporin-resistant Enterobacteriaceae

ObjectiveCurrent phenotypic methods for extended-spectrum β-lactamase (ESBL), AmpC β-lactamase (AmpC), and carbapenemases fail to detect isolates that co-produce other classes of β-lactamases. In this study, we have developed a novel assay (Applied Multiplex Disk Method: AMU-DM) for the phenotypic detection and identification of β-lactamases produced by Enterobacteriaceae. MethodsWe evaluated the performance of the method by comparison with PCR results for 78 Enterobacteriaceae clinical isolates that were positive by the ESBL screening test and negative by the ESBL confirmation test. Additionally, one NCTC strain and four ATCC strains were also included in the test population for the study as reference. ResultsFor 79/83 (95%) isolates tested, the AMU-DM results matched those obtained by PCR. The concordance rates were 31/31 (100%), 11/11 (100%), 3/3 (100%), 0/1 (0%), 15/15 (100%), 16/19 (84%), and 3/3 (100%) for AmpC, ESBL and AmpC co-production, Klebsiella pneumoniae carbapenemase (KPC), KPC and ESBL co-production, metallo β-lactamase (MBL), MBL and ESBL co-production, and MBL and AmpC co-production, respectively. ConclusionThe AMU-DM is convenient to perform, economical, and highly sensitive in identifying ESBLs, AmpCs, and carbapenemases. Our method may be useful in clinical settings for the implementation of relevant infection control measures and for surveillance purposes.

Using the best available data to estimate the cost of antimicrobial resistance: a systematic review

BackgroundValuation of the economic cost of antimicrobial resistance (AMR) is important for decision making and should be estimated accurately. Highly variable or erroneous estimates may alarm policy makers and hospital administrators to act, but they also create confusion as to what the most reliable estimates are and how these should be assessed. This study aimed to assess the quality of methods used in studies that quantify the costs of AMR and to determine the best available evidence of the incremental cost of these infections.MethodsIn this systematic review, we searched PubMed, Embase, Cinahl, Cochrane databases and grey literature sources published between January 2012 and October 2016. Articles reporting the additional burden of Enterococcus spp., Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) resistant versus susceptible infections were sourced. The included studies were broadly classified as reporting oncosts from the healthcare/hospital/hospital charges perspective or societal perspective. Risk of bias was assessed based on three methodological components: (1) adjustment for length of stay prior to infection onset and consideration of time-dependent bias, (2) adjustment for comorbidities or severity of disease, and (3) adjustment for inappropriate antibiotic therapy.ResultsOf 1094 identified studies, we identified 12 peer-reviewed articles and two reports that quantified the economic burden of clinically important resistant infections. Two studies used multi-state modelling to account for the timing of infection minimising the risk of time dependent bias and these were considered to generate the best available cost estimates. Studies report an additional CHF 9473 per extended-spectrum beta-lactamases -resistant Enterobacteriaceae bloodstream infections (BSI); additional €3200 per third-generation cephalosporin resistant Enterobacteriaceae BSI; and additional €1600 per methicillin-resistant S. aureus (MRSA) BSI. The remaining studies either partially adjusted or did not consider the timing of infection in their analysis.ConclusionsImplementation of AMR policy and decision-making should be guided only by reliable, unbiased estimates of effect size. Generating these estimates requires a thorough understanding of important biases and their impact on measured outcomes. This will ensure that researchers, clinicians, and other key decision makers concerned with increasing public health threat of AMR are accurately guided by the best available evidence.

ESCMID-EUCIC clinical guidelines on decolonization of multidrug-resistant Gram-negative bacteria carriers

ScopeThe aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings. MethodsThese evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations. RecommendationsThe panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints.

Admission prevalence of colonization with third-generation cephalosporin-resistant Enterobacteriaceae and subsequent infection rates in a German university hospital.

BackgroundMany patients admitted to a hospital are already colonized with multi-drug resistant organisms (MDRO) including third-generation cephalosporin-resistant Enterobacteriaceae (3GCREB). The aim of our study was to determine the prevalence of rectal 3GCREB colonization at admission to a large German university hospital and to estimate infection incidences. In addition, risk factors for 3GCREB colonization were identified.Materials/MethodsIn 2014 and 2015, patients were screened for rectal colonization with 3GCREB and filled out a questionnaire on potential risk factors at admission to a non-intensive care unit (non-ICU). All patients were retrospectively monitored for bacterial infections. Descriptive, univariable and multivariable logistic regression analyses were conducted to identify risk factors for 3GCREB colonization at admission.ResultsOf 4,013 patients included, 10.3% (n = 415) were rectally colonized with 3GCREB at admission. Incidence of nosocomial infections was 3.5 (95% CI 2.0–6.1) per 100 patients rectally colonized with 3GCREB compared to 2.3 (95% CI 1.8–3.0, P = 0.213) per 100 3GCREB negative patients.Independent risk factors for 3GCREB colonization were prior colonization / infection with MDRO (OR 2.30, 95% CI 1.59–3.32), prior antimicrobial treatment (OR 1.97, 95% CI 1.59–2.45), male sex (OR 1.38, 95% CI 1.12–1.70), prior travelling outside Europe (OR 2.39, 95% CI 1.77–3.22) and places of residence in the Berlin districts Charlottenburg-Wilmersdorf (OR 1.52, 95% CI 1.06–2.18), Friedrichshain-Kreuzberg (OR 2.32, 95% CI 1.44–3.74) and Mitte (OR 1.73, 95% CI 1.26–2.36).ConclusionsAdmission prevalence of rectal colonization with 3GCREB was high, while infection incidence did not significantly differ between patients rectally colonized or not with 3GCREB at hospital admission. In consequence, hospitals should prioritize improvement of standard precautions including hand hygiene to prevent infections among all patients irrespective of their 3GCREB status at hospital admission.

Trends of Incidence and Risk Factors of Ventilator-Associated Pneumonia in Elderly Patients Admitted to French ICUs Between 2007 and 2014.

To assess trends and risk factors of ventilator-associated pneumonia according to age, particularly in the elderly admitted to French ICUs between 2007 and 2014. Multicenter, prospective French national Healthcare-Associated Infection surveillance network of ICUs ("Réseau REA-Raisin"). Two-hundred fifty six ICUs in 246 settings in France. Included were all adult patients hospitalized greater than or equal to 48 hours in ICUs participating in the network. Ventilator-associated pneumonia surveillance over time. Overall and multidrug-resistant organism-related ventilator-associated pneumonia incidence rates were expressed per 1,000 intubation days at risk. Age was stratified into three groups: young (18-64 yr old), old (65-74 yr old), and very old (75+ yr old). Age-stratified multivariate mixed-effects Poisson regressions were undertaken to assess trends of ventilator-associated pneumonia incidence over time, with center as the random effect. Ventilator-associated pneumonia risk factors were also evaluated. Of 206,223 patients, 134,510 were intubated: 47.8% were young, 22.3% were old, and 29.9% were very old. Ventilator-associated pneumonia incidence was lower in the very old group compared with the young group (14.51; 95% CI, 16.95-17.70 vs 17.32; 95% CI, 16.95-17.70, respectively, p < 0.001). Methicillin-resistant Staphylococcus aureus and third-generation cephalosporin-resistant Enterobacteriaceae were identified more frequently in very old patients (p < 0.001 and 0.014, respectively). Age-stratified models disclosed that adjusted ventilator-associated pneumonia incidence decreased selectively in the young and old groups over time (adjusted incidence rate ratios, 0.88; 95% CI, 0.82-0.94; p < 0.001 and adjusted incidence rate ratios, 0.95; 95% CI, 0.86-1.04; p = 0.28, respectively). Male gender and trauma were independently associated with ventilator-associated pneumonia in the three age groups, whereas antibiotics at admission was a protective factor. Scheduled surgical ICU and immunodeficiency were risk factors of ventilator-associated pneumonia in the old group (p = 0.003). Ventilator-associated pneumonia incidence is lower but did not decrease over time in very old patients compared with young patients.

High admission prevalence of fluoroquinolone resistance in third-generation cephalosporin-resistant Enterobacteriaceae in German university hospitals.

Fluoroquinolone resistance (FQR) in third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) presents serious limitations to antibiotic therapy. The aim of this study was to investigate whether the FQR proportion among 3GCRE differs between community-acquired (CA) and hospital-acquired (HA) isolates. In a prospective observational study covering 2014 and 2015, we monitored the occurrence of 3GCRE in adult hospitalized patients in six German university hospitals. 3GCRE clinical isolates were subdivided into CA and HA. Multivariable analysis identified factors associated with in vitro non-susceptibility to ciprofloxacin. The dataset included 5721 3GCRE isolates of which 52.9% were HA and 52.7% exhibited FQR. Interestingly, the FQR proportion was higher in CA 3GCRE than in HA 3GCRE (overall, 60.1% versus 46.2%, respectively, P < 0.001). Multivariable analysis adjusting for age confirmed community acquisition as a risk factor for FQR [adjusted rate ratio (aRR) 1.33, 95% CI 1.17-1.53]. Escherichia coli and Klebsiella spp. were associated with a much higher FQR proportion than other Enterobacteriaceae species (aRR 8.14, 95% CI 6.86-9.65 and aRR 7.62 with 95% CI 6.74-8.61, respectively). The high FQR proportion observed among CA 3GCRE, particularly in E. coli and Klebsiella spp., indicates that selection pressure in the outpatient setting needs to be addressed with antibiotic stewardship and other interventions in order to limit further spread of MDR.