Carbapenemase-producing Enterobacteria Research Articles

Factors associated with colonization by carbapenem-resistant enterobacteria in oncological patients: a case-control study

Introduction: Colonization and infections caused by Carbapenemase Producing Enterobacteria (CPE) are a global problem, being associated with an increase in hospitalization time, costs for health services, and morbidity and mortality rates. Oncologic patients represent a group of special interest and there are few studies involving CPE colonization among these patients. Aim: to investigate factors associated with colonization in cancer patients. Outlining: Case-control study developed in a tertiary reference hospital in cancer treatment in Porto Alegre, Brazil, from January to December 2017. The population consisted of patients diagnosed with cancer in clinical or surgical hospitalization. Results: The univariate analysis showed that variables associated with colonization by CPE were age, male sex, tumors with bone type of surgical hospitalization, number of intra-hospital transfers since hospitalization, hospitalization time >30 days, ICU hospitalization in the last 30 days, ICU time more than 15 days, surgical procedure in the last 30 days, use of antibiotics in the last 30 days, presence of tumor wound, and KPC infection. After multivariate analysis, male sex, external hospital as origin, hospital stay longer than 30 days, antibiotic use in the last 30 days, and presence of tumor wound, remained associated with EPC colonization. Use of aminoglycosides, and linezolide were associated with CPE colonization. Implications: We identified variables associated with CPE colonization in oncologic patients. Our results may indicate actions to prevent CPE colonization and consequent development of infections.

ESBL and carbapenemase-producing Enterobacteriaceae in infectious pleural effusions: current epidemiology at Hôpital du Mali.

Antimicrobial resistance (AMR) is a global health concern, with extended-spectrum β-lactamases (ESBLs) and carbapenemases being major contributors. Pleural infection (PI) is a severe condition in West Africa, complicated by AMR. This study aimed to investigate the prevalence and molecular characteristics of ESBL and carbapenemase-producing enterobacteria in pleural effusions in Mali. Pleural fluid samples from 526 patients with pleuritis were analyzed. Enterobacterial species were isolated and identified, and the prevalence of resistance genes (blaOXA-48, blaNDM-1, blaKPC, blaTEM, blaSHV) and virulence factors was determined. Among the patients, 110 were diagnosed with enterobacterial pleuritis. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were the main pathogens identified. Resistance to β-lactams and cephalosporins was high, while carbapenems showed good activity. ESBL production was detected in 33.6% of isolates, with blaTEM being the most common gene. Carbapenemase gene (blaNDM-1) was found in three isolates. The study highlights the high prevalence of multidrug-resistant bacteria and the need for appropriate antibiotic selection based on local resistance patterns. Understanding the molecular characteristics of resistance is crucial for optimizing patient care and developing effective therapeutic strategies. Further research is needed to monitor and control AMR in PIs in Mali.

Trends in Antibiotic-Resistant Bacteria Isolated from Screening Clinical Samples in a Tertiary Care Hospital over the 2018-2022 Period.

To assess the putative impact of the COVID-19 pandemic on multidrug-resistant (MDR) bacteria recovered from routine screening samples and, more globally, the trends in time to first positive screening sample and carriage duration of those bacteria in patients admitted to a tertiary hospital, data from laboratory results were retrospectively mined over the 2018-2022 period. No significant differences could be found in the number of positive patients or MDR isolates per year, time to positive screening, or carriage duration. Extended-spectrum beta-lactamase producers were dominant throughout the studied period but their relative proportion decreased over time as well as that of meticillin-resistant Staphylococcus aureus. Meanwhile, carbapenemase-producing enterobacteria (CPE) proportion increased. Among the 212 CPE isolates, Klebsiella pneumoniae and Escherichia coli were the more frequent species but, beginning in 2020, a significant rise in Enterobacter cloacae complex and Citrobacter freundii occurred. OXA48 was identified as the leading carbapenemase and, in 2020, a peak in VIM-producing enterobacteria linked to an outbreak of E. cloacae complex during the COVID-19 pandemic was singled out. Finally, a worrisome rise in isolates producing multiple carbapenemases (NDM/VIM and mostly NDM/OXA48) was highlighted, especially in 2022, which could lead to therapeutic dead-ends if their dissemination is not controlled.

Surveillance of antibiotic resistance in the northern zone of Senegal: Molecular characterization of beta-lactam resistance genes in Enterobacteriaceae (extended spectrum beta-lactamase, plasmid cephalosporinases, carbapenemases).

Introduction: With the increase in bacterial resistance to antibiotics, policies are being implemented on a national scale. These resistances are multiple, especially in enterobacteria, and represent a real public health problem due to the difficulty of their treatment. The objective of this work was to identify ESBL, cephalosporinase and carbapenemase producing enterobacteria in laboratories in the northern part of Senegal and to compare the mechanisms involved. Materials and methods: This is a retrospective study conducted at the Saint-Louis Regional Hospital and the Microbiology Unit of the Pasteur Institute of Dakar. Bacterial strains were collected between January and June 2021 in eight bacteriology laboratories in the regions of Saint-Louis, Louga and Matam. Bacterial identification was done by studying morphological, cultural and biochemical characteristics using an API® 20 E gallery and the MALDI-TOFF technique. The antibiogram was performed by the disc diffusion method according to the CA-SFM version 2021 procedure including the search for specific resistances (ESBL). The ESBL genes (CTX, TEM, OXA, and SHV) were identified by polymerase chain reaction (PCR) with specific primers and then analyzed by gel electrophoresis. Results: Forty-five strains of Enterobacteriaceae were ESBL producers and each had at least one beta-lactam resistance gene. The CTX-M gene was found in all strains, followed by the OXA (64.44%), TEM (53.33%) and SHV (20%) genes. A simultaneous presence of these 4 genes was noted in 6 isolates (13.33%). Apart from resistance to ertapenem, all strains were sensitive to imipenem. For quinolones, almost all strains (93%) were resistant. Conclusion: These results show the need to reinforce the surveillance of ESBL-producing Enterobacteriaceae in the Senegal area. These important data should help to orientate strategies for the reduction of MRBs and their dissemination in the community.

Direct Colorimetry of Imipenem Decomposition as a Novel Cost-Effective Method for Detecting Carbapenemase-Producing Enterobacteria.

ABSTRACTIn the absence of a molecule that would collectively inhibit both metallo-β-lactamases and serine-reactive carbapenemases, containment of their genes is the main weapon currently available for confronting carbapenem resistance in hospitals. Cost-effective methodologies rapidly detecting carbapenemase-producing enterobacteria (CPE) would facilitate such measures. Herein, a low-cost CPE detection method was developed that was based on the direct colorimetry of the yellow shift caused by the accumulation of diketopiperazines—products of the acid-catalyzed imipenem oligomerization—induced by carbapenemase action on dense solutions of imipenem/cilastatin. The reactions were studied by spectrophotometry in the visible spectrum using preparations of β-lactamases from the four molecular classes. The effects of various buffers on reaction mixtures containing the potent carbapenemases NDM-1 and NMC-A were monitored at 405 nm. Optimal conditions were used for the analysis of cell suspensions, and the assay was evaluated using 66 selected enterobacteria, including 50 CPE as well as 16 carbapenemase-negative strains overexpressing other β-lactamases. The development of the yellow color was specific for carbapenemase-containing enzyme preparations, and the maximum intensity was achieved in acidic or unbuffered conditions in the presence of zinc. When applied on bacterial cell suspensions, the assay could detect CPE with 98% sensitivity and 100% specificity, with results being comparable to those obtained with the Carba NP technique. Direct colorimetry of carbapenemase-induced imipenem decomposition required minimum reagents while exhibiting high accuracy in detecting CPE. Therefore, it should be considered for screening purposes after further clinical evaluation.IMPORTANCE Currently, the spread of multidrug-resistant (MDR) carbapenemase-producing enterobacteria (CPE), mostly in the clinical setting, is among the most pressing public health problems worldwide. In order to effectively control CPE, use of reliable and affordable methods detecting carbapenemase genes or the respective β-lactamases is of vital importance. Herein, we developed a novel method, based on a previously undescribed phenomenon, that can detect CPE with few reagents by direct colorimetry of bacterial suspensions and imipenem/cilastatin mixtures.

Pervasive transmission of a carbapenem resistance plasmid in the gut microbiota of hospitalized patients.

Introductory paragraphInfections caused by carbapenemase-producing enterobacteria (CPE) are a major concern in clinical settings worldwide. Two fundamentally different processes shape the epidemiology of CPE in hospitals: the dissemination of CPE clones from patient to patient (between-patient transfer), and the transfer of carbapenemase-encoding plasmids between enterobacteria in the gut microbiota of individual patients (within-patient transfer). The relative contribution of each process to the overall dissemination of carbapenem resistance in hospitals remains poorly understood. Here, we used mechanistic models combining epidemiological data from more than 9,000 patients with whole genome sequence information from 250 enterobacteria clones to characterise the dissemination routes of a pOXA-48-like carbapenemase-encoding plasmid in a hospital setting over a two-year period. Our results revealed frequent between-patient transmission of high-risk pOXA-48-carrying clones, mostly of Klebsiella pneumoniae and sporadically Escherichia coli. The results also identified pOXA-48 dissemination hotspots within the hospital, such as specific wards and individual rooms within wards. Using high-resolution plasmid sequence analysis, we uncovered the pervasive within-patient transfer of pOXA-48, suggesting that horizontal plasmid transfer occurs in the gut of virtually every colonised patient. The complex and multifaceted epidemiological scenario exposed by this study provides insights for the development of intervention strategies to control the in-hospital spread of CPE.

Prevalence and molecular characterisation of carbapenemase-producing Enterobacterales in an outbreak-free setting in a single hospital in Uruguay

ObjectivesThis study aimed to characterise all carbapenemase-producing enterobacteria (CPE) isolates obtained from an outbreak-free setting in Uruguay. MethodsWe studied 12 CPE isolated from Hospital de Clínicas between 2012–2016. Bacterial identification and antibiotic susceptibility testing were performed using VITEK®2 and Sensititre or agar dilution, respectively. Antimicrobial resistance genes and mobile genetic elements were identified by PCR and sequencing. Multilocus sequence typing was performed for Klebsiella pneumoniae. Plasmid conjugation was assessed, plasmid size was estimated by S1-PFGE and plasmid incompatibility groups were sought by PCR. ResultsAmong 8364 enterobacteria, 12 CPE were isolated from urine, blood culture, wound, peritoneal fluid and punch samples. NDM-1 was the most prevalent carbapenemase, followed by VIM-2 and KPC-2. All isolates were resistant to gentamicin, cefotaxime, ceftazidime, trimethoprim/sulfamethoxazole, ciprofloxacin and imipenem and were susceptible to fosfomycin. We characterised six class 1 integrons: dfrA12–orfF–aadA2; aacA4–blaOXA-2–orfD; aadB–aadA2; dfrA1; aadB–blaOXA-10–aadA1; and blaVIM-2-dfrA7. An association between various aminoglycoside, β-lactam and fluoroquinolone resistance genes were observed, some of them located in transferable plasmids belonging to incompatibility groups IncC, IncHI1 and IncM1. We described a new composite transposon (assigned Tn6935) including blaNDM-1 flanked by two directly-oriented copies of a Tn3-like element ISKox2-like family transposase. The sequence types of K. pneumoniae isolates were ST11, ST14 and ST661. ConclusionsThe presence of CPE is sporadic and could be due to measures taken by the Public Health Committee. Nevertheless, the coexistence of several resistance mechanisms and their presence in conjugative plasmids and high-risk clones is worrisome.

Infections Caused by Carbapenem-Resistant Enterobacterales: Epidemiology, Clinical Significance, and Possibilities for Antibiotic Therapy Optimization

The resistance of Enterobacterales to carbapenems can be realized by different mechanisms, but the most common one is enzymatic, associated with the production of carbapenemases. Carbapenemases of enterobacteria are characterized by a wide variety;they are represented in three classes of beta-lactamases. The most well-known carbapenemases belong to classes A (KPC, GESenzymes), D (OXA-48), and B (metalloenzymes — NDM, VIM, IMP). Detailed clinical and microbiological characteristics of carbapenemases are given, as well as recommendations for their detection. Carbapenemases are widespread, and the paper discusses the geographical distribution of carbapenemases in different regions of the world; OXA-48 and NDM are the most widelydistributed enzymes in Russia. The clinical significance of carbapenemases and risk factors for these infections are discussed,including the following: 1) previous carbapenem therapy; 2) high levels of carbapenemases in the Department; 3) colonization of theintestine with carbapenemase-producing enterobacteria; 4) traveling to regions with a high prevalence of carbapenemases (4th and5th epidemiological levels). The possibilities of antibacterial therapy of infections caused by carbapenem-resistant enterobacteriaare discussed, the clinical and pharmacological characteristics of different antibiotics (ceftazidime/avibactam, aztreonam, carbapenems, polymyxins, tigecycline, fosfomycin), their effectiveness and treatment options are analyzed in detail. Current clinicaldata showing the effectiveness of ceftazidime/avibactam monotherapy for infections caused by carbapenemase producers OXA-48and KPC are presented. Practical issues of management of such patients are discussed. Algorithms for empirical and targeted therapy of infections caused by carbapenem-resistant enterobacteria are presented.

Colonization with multiresistant bacteria in acute hospital care: the association of prior antibiotic consumption as a risk factor.

Antibiotic resistance poses a worldwide threat and knowledge concerning risk factors for colonization with multiresistant bacteria (MRB) is limited. To examine the impact of prior antibiotic consumption on MRB colonization, with focus on type of antibiotic and timeline between antibiotic prescription and MRB colonization. A nationwide case-control study was conducted and adults visiting emergency departments were invited to participate. All patients were swabbed in the throat, nose and rectum, and analysed for colonization with ESBL-producing Enterobacteriaceae (ESBL-E), MRSA, carbapenemase-producing enterobacteria and VRE. Antibiotic history 2 years prior to enrolment was collected at an individual level through a national register. Multivariate analyses were performed to examine the association between antibiotic consumption and MRB status. A subgroup analysis of ESBL-E-colonized cases was made. We included 256 patients colonized with MRB and 4763 controls. In the 2 years prior to study inclusion, 77% of cases and 68% of controls had at least one antibiotic prescription (P = 0.002). We found a significant increase in risk of colonization with ESBL-E if penicillins (OR = 1.58-1.65) or fluoroquinolones (OR = 2.25-6.15) were prescribed. The analysis of all MRB-colonized patients showed similar results. An assessment of the timeline showed a significant increase in risk of colonization up to 2 years after exposure to penicillins, fluoroquinolones and macrolides. The prevalence of ESBL-E colonization was related to fluoroquinolone, macrolide and penicillin consumption for at least 2 years after antibiotic treatment.

Carrier prevalence and risk factors for colonisation of multiresistant bacteria in Danish emergency departments: a cross-sectional survey.

ObjectivesThe aim of this study was to describe the carrier prevalence and demographic variation of four different multiresistant bacteria (MRB) among acute patients in Danish emergency departments (EDs): methicillin-resistant Staphylococcus aureus (MRSA), carbapenemase-producing enterobacteria (CPE), extended-spectrum beta-lactamase-producing enterobacteria (ESBL) and vancomycin-resistant enterococci (VRE), and to analyse the association of MRB carriage to a range of potential risk factors.DesignMulticentre descriptive and analytic cross-sectional survey.SettingEight EDs and four clinical microbiology departments in Denmark.ParticipantsAdults visiting the ED.Main outcome measuresSwabs from nose, throat and rectum were collected and analysed for MRSA, ESBL, VRE and CPE. The primary outcome was the prevalence of MRB carriage, and secondary outcomes relation to risk factors among ED patients.ResultsWe included 5117 patients in the study. Median age was 68 years (54–77) and gender was equally distributed. In total, 266 (5.2%, 95% CI 4.6 to 5.8) were colonised with at least one MRB. No significant difference was observed between male and female patients, between age groups and between university and regional hospitals. Only 5 of the 266 patients with MRB were colonised with two of the included bacteria and none with more than two. CPE prevalence was 0.1% (95% CI 0.0 to 0.2), MRSA prevalence was 0.3% (95% CI 0.2 to 0.5), VRE prevalence was 0.4% (95% CI 0.3 to 0.6) and ESBL prevalence was 4.5% (95% CI 3.9 to 5.1). Risk factors for MRB carriage were previous antibiotic treatment, previous hospital stay, having chronic respiratory infections, use of urinary catheter and travel to Asia, Oceania or Africa.ConclusionEvery 20th patient arriving to a Danish ED brings MRB to the hospital. ESBL is the most common MRB in the ED. The main risk factors for MRB carriage are recent antibiotic use and travel abroad.Trial registration number NCT03352167;Post-results.

Multicentre investigation of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in Bulgarian hospitals – Interregional spread of ST11 NDM-1-producing K. pneumoniae

AimThe aim of this study was to investigate the mechanisms of beta-lactam-resistance and the clonal relatedness of carbapenem-nonsusceptible Klebsiella pneumoniae and Escherichia coli isolates, collected consecutively in eight centers in five Bulgarian cities from November 2014 to March 2018. Carbapenemase-producing enterobacteria were detected in all but one centers. Overall, 104 K. pneumoniae and one E. coli were analysed. Materials and methodsAntimicrobial susceptibility and beta-lactamases were analysed. Conjugation experiments, plasmid fingerprinting and replicon typing, as well as MLST and ERIC-PCR were carried out. ResultsKPC-2 (51%) and NDM-1 (47%) were the main carbapenemases identified. KPC-2 producing K. pneumoniae were classified into 10 MLST-types. The four dominating MLST-types ST29, ST15, ST336 and ST902 comprised 79% of the KPC-2 producers. All but one of the NDM-1 producing isolates belonged to the MLST-type ST11 and were found in seven centers. Furthermore, single K. pneumoniae isolates producing VIM-1 (ST147) and OXA-48 (ST15) were identified. In addition to the carbapenemases, the ESBLs CTX-M-15, CTX-M-3, and SHV-12 as well as AmpC enzyme CMY-4 were found. The FIIAs-replicon-type was found in all KPC-2 producers while the A/C-replicons dominated in NDM-1 producing isolates. The single NDM-1 producing E. coli was determined as MLST-Type ST10 (Warwick scheme). ConclusionThe interregional clonal expansion of NDM-1 producing ST11 K. pneumoniae and the dissemination of blaKPC-2 carrying plasmids were responsible for the spread of carbapenemase-producing K. pneumoniae in Bulgaria. Our findings highlight the urgency to prevent dissemination of these highly transmissible and dangerous lineages.

Evolution of the antibiotic-resistance of microorganisms causing urinary tract infections: A 4-year epidemiological surveillance study in a hospital population

BackgroundUrinary tract infections (UTIs) are the leading cause of infection in hospitalised patients. In this study, we describe the most common pathogens involved in the development of UTIs in hospitalised patients, their antibiotic-sensitivity profile and the activity evolution of antibiotics in standard use for treating these infections. MethodsWe retrospectively assessed the results of cultures and antibiograms from urine samples from adult patients hospitalised in the Hospital Complex Virgen de la Nieves (Granada, Spain) with a microbiological confirmation of UTI between January 2013 and December 2016. ResultsWe identified 4347 microorganisms (3969 bacteria and 378 yeasts). During the 4years of the study, Escherichia coli was the most common species isolated in both sexes; however, 62.9% of the UTIs were caused by other microorganisms. The presence of multiresistant microorganisms such as Acinetobacter spp. (1.2%) and extended-spectrum beta-lactamase-producing enterobacteria (10.0%) and carbapenemase-producing enterobacteria (0.3%) were also relevant findings. Imipenem, piperacillin–tazobactam and fosfomycin presented activity rates above 80%, considering all causal microorganisms of UTI, while the other tested antibiotics presented activity rates below 70%. ConclusionImipenem and piperacillin–tazobactam were the most active antibiotics in hospital use, which makes them first-line antibiotics in the empiric treatment of UTIs in this healthcare setting. The use of other antibiotics should be limited to conditions of demonstrated or highly probable sensitivity.

Evolución de la resistencia a antibióticos de microorganismos causantes de infecciones del tracto urinario: un estudio de vigilancia epidemiológica de 4 años en población hospitalaria

BackgroundUrinary tract infections (UTIs) are the leading cause of infection in hospitalised patients. In this study, we describe the most common pathogens involved in the development of UTIs in hospitalised patients, their antibiotic-sensitivity profile and the activity evolution of antibiotics in standard use for treating these infections. MethodsWe retrospectively assessed the results of cultures and antibiograms from urine samples from adult patients hospitalised in the Hospital Complex Virgen de la Nieves (Granada, Spain) with a microbiological confirmation of UTI between January 2013 and December 2016. ResultsWe identified 4,347 microorganisms (3,969 bacteria and 378 yeasts). During the 4years of the study, Escherichia coli was the most common species isolated in both sexes; however, 62.9% of the UTIs were caused by other microorganisms. The presence of multiresistant microorganisms such as Acinetobacterspp. (1.2%) and extended-spectrum beta-lactamase-producing enterobacteria (10.0%) and carbapenemase-producing enterobacteria (0.3%) were also relevant findings. Imipenem, piperacillin-tazobactam and fosfomycin presented activity rates above 80%, considering all causal microorganisms of UTI, while the other tested antibiotics presented activity rates below 70%. ConclusionImipenem and piperacillin-tazobactam were the most active antibiotics in hospital use, which makes them first-line antibiotics in the empiric treatment of UTIs in this healthcare setting. The use of other antibiotics should be limited to conditions of demonstrated or highly probable sensitivity.

Colonization of long-term care facility residents in three Italian Provinces by multidrug-resistant bacteria

BackgroundRationale and aims of the study were to compare colonization frequencies with MDR bacteria isolated from LTCF residents in three different Northern Italian regions, to investigate risk factors for colonization and the genotypic characteristics of isolates. The screening included Enterobacteriaceae expressing extended-spectrum β-lactamases (ESβLs) and high-level AmpC cephalosporinases, carbapenemase-producing Enterobacteriaceae, Pseudomonas aeruginosa or Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).MethodsUrine samples and rectal, inguinal, oropharyngeal and nasal swabs were plated on selective agar; resistance genes were sought by PCR and sequencing. Demographic and clinical data were collected.ResultsAmong the LTCF residents, 75.0% (78/104), 69.4% (84/121) and 66.1% (76/115) were colonized with at least one of the target organisms in LTCFs located in Milan, Piacenza and Bolzano, respectively. ESβL producers (60.5, 66.1 and 53.0%) were highly predominant, mainly belonging to Escherichia coli expressing CTX-M group-1 enzymes. Carbapenemase-producing enterobacteria were found in 7.6, 0.0 and 1.6% of residents; carbapemenase-producing P. aeruginosa and A. baumannii were also detected. Colonization by MRSA (24.0, 5.7 and 14.8%) and VRE (20.2, 0.8 and 0.8%) was highly variable. Several risk factors for colonization by ESβL-producing Enterobacteriaceae and MRSA were found and compared among LTCFs in the three Provinces. Colonization differences among the enrolled LTCFs can be partially explained by variation in risk factors, resident populations and staff/resident ratios, applied hygiene measures and especially the local antibiotic resistance epidemiology.ConclusionsThe widespread diffusion of MDR bacteria in LTCFs within three Italian Provinces confirms that LTCFs are an important reservoir of MDR organisms in Italy and suggests that future efforts should focus on MDR screening, improved implementation of infection control strategies and antibiotic stewardship programs targeting the complex aspects of LTCFs.

Risk factors for colonization by carbapenemase-producing enterobacteria at admission to a Surgical ICU: A retrospective study

IntroductionIn 2011, a hospital-wide outbreak of OXA-48 producing Klebsiella pneumoniae occurred in our hospital, an epidemiological setting of high ESBL-producing K. pneumoniae rates. This study identifies risk factors for colonization with carbapenemase-producing enterobacteria (CPE) at Surgical Intensive Care Unit (SICU) admission. MethodsA 2-year retrospective study was performed in all patients admitted to the SICU that following routine had a rectal swab collected upon admission. ResultsOf 254 patients admitted, 41 (16.1%) harbored CPE (five showing two carbapenemase-producing isolates). Most frequent carbapenemase-producing isolates and carbapenemases were K. pneumoniae (39/46, 84.8%) and OXA-48 (31/46; 76.1%), respectively. Carriers significantly had higher rates of chronic renal disease, previous digestive/biliary endoscopy, hospitalization, ICU/SICU admission, intraabdominal surgery, and antibiotic intake, as well as higher median values of clinical scores (SOFA, SAPS II and APACHE II). In the multivariate analysis (R2=0.309, p<0.001), CPE carriage was associated with prior administration of 3rd–4th generation cephalosporins (OR=27.96, 95%CI=6.88, 113.58, p<0.001), β-lactam/β-lactamase inhibitor (OR=11.71, 95%CI=4.51, 30.43, p<0.001), abdominal surgery (OR=6.33, 95%CI=2.12, 18.89, p=0.001), and prior digestive/biliary endoscopy (OR=3.88, 95%CI=1.56, 9.67, p=0.004). ConclusionsA strong association between production of ESBLs and carriage of CPE (mainly OXA-48 producing K. pneumoniae) was found. According to the model, the co-selection of β-lactamases by previous exposure to broad-spectrum cephalosporins and β-lactam/β-lactamase inhibitors (with lower relative risk), abdominal surgery and prior digestive/biliary endoscopy were factors associated with CPE carriage.

Retrospective and prospective evaluation of the Carbapenem inactivation method for the detection of carbapenemase-producing Enterobacteriaceae.

BackgroundThere is an urgent need for accurate and rapid diagnostic tests to identify carbapenemase producing enterobacteria (CPE). Here, we have evaluated the Carbapenem Inactivation Method (CIM) test to detect CPEs from cultured colonies.MethodsA total of 256 enterobacterial isolates were used to evaluate the performance of the CIM in comparison to Carba NP test and molecular detection used a reference method. Ninety three well-characterized isolates (including 29 non-CPE and 63 CPEs of worldwide origin) with decreased susceptibility to at least one carbapenem were used to (i) evaluate the efficacy of CIM test and (ii) to compare it to the Carba NP test. We also tested different carbapenems to determine the best substrate for this test. Finally, the CIM test was then evaluated prospectively against 164 isolates referred to the French National Reference Center (NRC) for Antimicrobial Resistance from may 2016 to july 2016.ResultsBased on the results of this retrospective study, sensitivity and specificity of the CIM and the Carba NP test were 92.1% and 100%, respectively. We demonstrated that the meropenem was the best substrate to perform the CIM test since sensitivity and specificity were 81.1% and 100% using ertapenem disk, and 100% and 65,6% using imipenem disk, and respectively. Taking in account the results of retrospective and prospective studies, CIM and Carba NP tests have similar sensitivity, specificity, positive predictive value and negative predictive values being 96.3%, 98.9%, 99.0% and 98.4% for the CIM test versus 96.9%, 100%, 100% and 100% for the Carba NP test.ConclusionsOur results confirm that the CIM test may be a useful tool for the reliable confirmation of carbapenemase-activity in enterobacterial isolates, especially in clinical microbiological laboratories with limited resources, no trained personnel, and no specialized equipment.

Bloodstream Infections in Hematological Cancer Patients Colonized By Multiresistant Bacteria: Final Results of a Multicentric Prospective Observational Seifem Study

▪Introduction. Multiresistant (MR) bacteria colonization is considered predictive of related bloodstream infections (BSI), which are worrisome among hematological patients (pts). Few data are available about the actual incidence of MR colonization and the probability of developing a BSI in this population. A multicentric prospective observational study has been carried out within the SEIFEM group, with the aim of detecting the incidence of MR bacterial colonization and the probability of developing MR BSI in hematological pts.Patients and Methods. Between March 1st and August 31st 2015, all pts with a hematological neoplasm admitted to 18 Italian Centres participating to SEIFEM were screened for MR colonization with a rectal swab; cultures of other sites were performed if clinically indicated. Patients showing MR bacterial colonization were recorded in a database where the occurrence of any BSI was correlated with age, gender, type and phase of disease, stem cell transplantation (SCT), presence of invasive devices, type of colonizing bacteria.Results. During a 6-month period, 189 pts with MR colonization were observed. Incidence was 8.9% among all admissions (189/2122). Median age was 59y (range 0-89) and M/F ratio 116/73. Eighty-two pts were affected by acute leukemia, 75 by lymphoma, 24 by myeloma, 6 by chronic myeloproliferative/myelodysplastic syndromes and 2 by aplastic anemia. Forty-four pts underwent SCT (28 autologous and 16 allogeneic). Vancomycin resistant enterococci (VRE) were responsible for colonization in 15 (7.9%) pts, extended spectrum beta-lactamases producing (ESBL-P) enterobacteria in 80 (42.3%) and carbapenemase producing (CP) Gram-Negative Rods (GNR) in 108 (57.1%). Thirteen of 14 pts with multiple colonizations had both ESBL and carbapenemase producing enterobacteria. Multivariate analysis of risk factors for type of MDR colonization showed that a complete hematologic remission was associated to ESBL-P enterobacteria colonization, but protective for CP strains (OR 2, 1.1-3.7, p=0.02 and 0.43, 0.23-0.79, p=0.006, respectively). Overall, 62 pts (32.8%) colonized with MR bacteria developed at least one BSI during the period of observation; 36 of them (58.1%; 19% of the whole series) developed BSI by the same pathogen (MRrel-BSI) (2 VRE, 14 ESBL-P E. coli, 2 ESBL-P K.pneumoniae, 1 ESBL-P E. aerogenes, 12 CP K. pneumoniae, 3 CP P. aeruginosa and 2 CP Acinetobacter spp). The rate of MRrel-BSI according to antibiotic resistance was 13.3% for VRE colonization, 19.5% for ESBL-P enterobacteria and 17.6% for CP GNR. CP K. pneumoniae, but not other CP enterobacteria, was predictive of MRrel-BSI (26.7%). In 82% of cases, MRrel-BSI occurred during neutropenia. At multivariate analysis of predictors of BSI, a relapsed/refractory hematological disease was associated to MRrel-BSI (OR 3.1, 1.4-6.7, p=0.005). Unrelated BSI were also observed in 32 pts (51.6%; 16.9% of the whole series), including 6 MR BSI (2 CP P. aeruginosa, 3 CP K. pneumoniae and 1 VRE). After a median follow-up of 80 days (range 0-270), 25 pts died (13.2%). Three-month overall survival (OS) of the entire cohort was 86%±2.9SE, being significantly lower for pts colonized with VRE (71%) and CP (82%) in comparison with those colonized with ESBL-P bacteria (97%, p=0.0018 and 0.0043 respectively) (Fig.1). Death was attributable to CP GNR related BSI in 5 pts and to VRE related BSI in 1. Multivariate analysis showed that CP GNR related BSI (OR 8.3, 2.2-30.5, p=0.001) and VRE related BSI (OR 87.9, 1.1-675.9, p=0.04), together with intensive care unit admission (OR 50.6, 4.5-570.9, p=0.001) were independent predictors of mortality at 30-days from known colonization, whereas having disease in complete remission was protective (OR 0.02, 0.001-0.43, p=0.01).Conclusions. Incidence of MR colonizing bacteria, particularly ESBL-P and CP GNR, affects nearly 10% of italian hematological cancer pts and results in a MRrel BSI in about one fifth of cases, mainly during neutropenia. MRrel-BSI are responsible for more than 50% of BSI observed in MR colonized pts and are significantly more frequent in relapsed/refractory hematologic disease. VRE and CP GNR colonizations but not ESBL-P are associated to lower OS and predict for a higher fatality of related BSI. Among CP enterobacteria, only K. pneumoniae is associated with MRrel-BSI. Empiric antibiotic treatment should be better tailored taking into account these results. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Physiological and molecular characteristics of carbapenem resistance in Klebsiella pneumoniae and Enterobacter aerogenes.

Bacterial resistance is a growing concern in the nosocomial environment in which Klebsiella pneumoniae and Enterobacter aerogenes play an important role due to their opportunism and carbapenemase-production. This work aimed to evaluate physiological and molecular characteristics of carbapenem-resistant K. pneumoniae and E. aerogenes isolated in a Brazilian tertiary hospital. In total, 42 carbapenem-resistant bacteria isolated from clinical specimens were included (21 K. pneumoniae and 21 E. aerogenes). Drug-sensitive K. pneumoniae (n = 27) were also included. Antimicrobial susceptibility and biocide tolerance patterns, hemolytic activity, tolerance to oxidative stress, and aggregative ability were assessed. Genetic markers related to carbapenem resistance, or ESBL-production were screened by PCR. Compared to drug-sensitive strains, carbapenem-resistant K. pneumoniae were more tolerant to biocides and to oxidative stress, and they displayed an increase in biofilm formation. The genetic markers blaKPC (95.2%) and blaTEM (90.5%) were the most frequent. Among the carbapenem-resistant E. aerogenes strains, blaKPC, and blaTEM were detected in all bacteria. Drug-sensitive E. aerogenes were not isolated in the same period. blaSHV, blaVIM, and blaCTX markers were also observed among carbapenem-resistant bacteria. Results suggest that carbapenemase-producing enterobacteria might show peculiar characteristics regarding their physiology associated with their environmental persistency, virulence, and multidrug resistance. The observed phenomenon may have implications not only for antimicrobial chemotherapy, but also for the prognosis of infectious diseases and infection control.

Risk factors for colonization by carbapenemase-producing enterobacteria at admission to a Surgical ICU: A retrospective study

IntroductionIn 2011, a hospital-wide outbreak of OXA-48 producing Klebsiella pneumoniae occurred in our hospital, an epidemiological setting of high ESBL-producing K. pneumoniae rates. This study identifies risk factors for colonization with carbapenemase-producing enterobacteria (CPE) at Surgical Intensive Care Unit (SICU) admission. MethodsA 2-year retrospective study was performed in all patients admitted to the SICU that following routine had a rectal swab collected upon admission. ResultsOf 254 patients admitted, 41 (16.1%) harbored CPE (five showing two carbapenemase-producing isolates). Most frequent carbapenemase-producing isolates and carbapenemases were K. pneumoniae (39/46, 84.8%) and OXA-48 (31/46; 76.1%), respectively. Carriers significantly had higher rates of chronic renal disease, previous digestive/biliary endoscopy, hospitalization, ICU/SICU admission, intraabdominal surgery, and antibiotic intake, as well as higher median values of clinical scores (SOFA, SAPS II and APACHE II). In the multivariate analysis (R2=0.309, p<0.001), CPE carriage was associated with prior administration of 3rd–4th generation cephalosporins (OR=27.96, 95%CI=6.88, 113.58, p<0.001), β-lactam/β-lactamase inhibitor (OR=11.71, 95%CI=4.51, 30.43, p<0.001), abdominal surgery (OR=6.33, 95%CI=2.12, 18.89, p=0.001), and prior digestive/biliary endoscopy (OR=3.88, 95%CI=1.56, 9.67, p=0.004). ConclusionsA strong association between production of ESBLs and carriage of CPE (mainly OXA-48 producing K. pneumoniae) was found. According to the model, the co-selection of β-lactamases by previous exposure to broad-spectrum cephalosporins and β-lactam/β-lactamase inhibitors (with lower relative risk), abdominal surgery and prior digestive/biliary endoscopy were factors associated with CPE carriage.

Bloodstream Infections in Hematological Cancer Patients Colonized By Multiresistant Bacteria: Results of a Multicentric Prospective Observational Seifem Study

▪Introduction. Incidence and mortality due to multiresistant (MR) bloodstream infections (BSI) are increasing in the last years among hematological patients (pts). Also rate of MR colonization seems to be relevant, but few data are available on the actual incidence of MR colonization and the probability of developing a BSI in hematological pts. In order to evaluate the incidence of MR bacterial colonization and the probability of developing MR BSI in hematological pts, we carried out a multicentric prospective observational study within the SEIFEM group.Patients and Methods. Since March 1st 2015, all cancer patients were screened at least for rectal swab at admission in 11 Hematology Centres participating to SEIFEM; culture of other sites were performed if clinically indicated. Patients showing MR bacterial colonization were recorded in a database where the occurrence of any BSI was correlated with age, gender, type and phase of haematological disease, stem cell transplantation (SCT), presence of invasive devices, type of colonizing bacteria.Results. During a 3-month period (March 1st -May 31st 2015), 75 pts with MR colonization were observed. Incidence was 9.8% among all admitted pts (75/764). Median age was 61y (range 20-81) and M/F ratio 46/29. Thirty-three pts were affected by acute leukemia (AL), 30 by lymphoma (Ly), 10 by myeloma (MM), 1 by myelofibrosis and 1 by aplastic anemia. Nineteen pts underwent SCT during the period of observation (11 autologous and 8 allogeneic, respectively). Vancomycin resistant enterococci (VRE) were responsible for colonization in 6 (8%) pts, extended spectrum β-lactamases producing (ESBL) enterobacteria in 29 (38.8%) and carbapenemase producing (CP) Gram-Negative Rods (GNR) in 49 (65.3%). Seven pts showed multiple colonizations. In 8 cases colonizing enterobacteria (6 E. coli, 1 E. cloacae, 1 P. mirabilis) were both ESBL and carbapenemase producers. Rectum was the most frequent site of colonization (70.7%). No risk factor for type of colonizing bacteria emerged except for previous intensive care unit stay for CP GNR colonization (p=0.02, chi-square test). Overall, 15 (20%) pts colonized with MR bacteria developed BSI by the same pathogen (MR related BSI) (1 VRE, 5 ESBL producing E. coli, 5 CP K. pneumoniae, 2 CP P. aeruginosa and 2 CP Acinetobacter spp). Therefore, rate of related BSI according to type of antibiotic resistance was 16.7% for VRE colonization, 17.2% for ESBL producing enterobacteria and 18.4% for CP GNR, respectively. Among CP enterobacteria, K. pneumoniae, but not other enterobacteria, was predictive of related BSI (25%). All but 2 related BSI occurred during neutropenia. At multivariate analysis, previous cephalosporin treatment was associated to related BSI (OR 0.25 [CI 0.07-0.91], p=0.03). Unrelated BSI were also observed in 15 pts (20%), including 3 MR BSI (2 CP P. aeruginosa and 1 CP K. pneumoniae). After a median follow-up of 61 days (range 30-116), 9 pts died (12%). Death was attributable to CP GNR related BSI in 3 pts. Multivariate analysis showed that CP GNR related BSI (OR 6.1, CI 1-36.2, p=0.04), together with a relapsed/refractory hematological disease (OR 10, CI 1.5-66.4, p=0.02) and presence of urinary catheter (OR 9.1, CI 1.3-62.1, p=0.02), was an independent predictor variable for death.Conclusions. Incidence of MR colonizing bacteria, particularly CP GNR, is quite high among hematological cancer pts and is associated with related BSI in a considerable proportion of them. Unrelated MR BSI may also occur. Previous antibiotic treatment with cephalosporins is a risk factor for MR related BSI and CP related BSI are predictive of death. Empiric antibiotic treatment should be planned taking into account these results. DisclosuresNo relevant conflicts of interest to declare.