Multiresistant Enterococci Research Articles

Comparing genome-scale metabolic models of the non-resistant Enterococcus faecalis ATCC 19433 and the multi-resistant Enterococcus faecalis V583

Enterococcus faecalis is a versatile lactic acid bacterium with a large variety of implications for humans. While some strains of this species are pathobionts being resistant against most of the common antibiotics, other strains are regarded as biological protectants or even probiotics. Accordingly, E. faecalis strains largely differ in the size and content of their accessory genome. In this study, we describe the genome-scale metabolic network reconstruction of E. faecalis ATCC 19433, a non-resistant human-associated strain. A comparison of the genome-scale metabolic model (GSM) of E. faecalis ATCC 19433 with a previously published GSM of the multi-resistant pathobiontic E. faecalis V583 reveals high similarities in the central metabolic abilities of these two human associated strains. This is reflected, e.g., in the identical amino acid auxotrophies. The ATCC 19433 strain, however, has a 14.1 % smaller genome than V583 and lacks the multiple antibiotic resistance genes and genes involved in capsule formation. Based on the measured metabolic fluxes at different growth rates, the energy demand at zero growth was calculated to be about 40 % lower for the ATCC 19433 strain compared to V583. Furthermore, the ATCC 19433 strain seems less prone to the depletion of amino acids utilizable for energy metabolism. This might hint at a lower overall energy demand of the ATCC 19433 strain as compared to V583.

Antibacterial activity evaluation of cambuí extract against multi-resistant Enterococcus faecium

Bacterial resistance is a global public health issue. Among these pathogens, Enterococcus faecium nosocomial has been highlighted due to its potential to cause bacteremia infections. The incidence of resistant Enterococcus faecium bacteremia has enhanced over time, thereby, it has caused high rates of mortality. Hence, it led to the interest in natural drugs. Plant extracts from the Myrtaceae family have a broad-spectrum antimicrobial action. Among the plants of this family, we can highlight cambuí, due to its wide variety of bioactive compounds such as phenolic compounds. Polyphenols are bioactive molecules that can inhibit the growth of resistant bacteria such as Enterococcus faecium. For this, the present study aimed to obtain bioactive extracts from cambuí using pressurized hot water to grow inhibition of multi-resistant Enterococcus faecium nosocomial. In the present study, antibacterial compounds were obtained after extraction kinetics over 120 minutes at a temperature of 50º C, a flow rate of 1 mL/min-1, and a constant pressure of 200 bar using water as the extraction solvent. Flavonoids and other phenolic compounds from cambuí extracts were quantified by spectrophotometric methods. The TSA using the well-diffusion method was used to verify the sensitivity of the bacterium Enterococcus faecium against cambuí aqueous extract. The results showed that the best extraction time was 60 minutes using 60 mL of water. The cambuí aqueous extract showed a relevant amount of flavonoids and other phenolic compounds, hence, this extract was able to inhibit the growth of the bacterium Enterococcus faecium resistant to Ampicillin, Imipenem, Vancomycin, and Teicoplanin.

Antimicrobial Resistance in Enterococcus spp. Isolates from Red Foxes (Vulpes vulpes) in Latvia.

Antimicrobial resistance (AMR) is an emerging public health threat and is one of the One Health priorities for humans, animals, and environmental health. Red foxes (Vulpes vulpes) are a widespread predator species with great ecological significance, and they may serve as a sentinel of antimicrobial resistance in the general environment. The present study was carried out to detect antimicrobial resistance, antimicrobial resistance genes, and genetic diversity in faecal isolates of red foxes (Vulpes vulpes). In total, 34 Enterococcus isolates, including E. faecium (n = 17), E. faecalis (n = 12), E. durans (n = 3), and E. hirae (n = 2), were isolated. Antimicrobial resistance to 12 antimicrobial agents was detected with EUVENC panels using the minimum inhibitory concentration (MIC). The presence of antimicrobial resistance genes (ARGs) was determined using whole-genome sequencing (WGS). Resistance to tetracycline (6/34), erythromycin (3/34), ciprofloxacin (2/34), tigecycline (2/34), and daptomycin (2/34) was identified in 44% (15/34) of Enterococcus isolates, while all the isolates were found to be susceptible to ampicillin, chloramphenicol, gentamicin, linezolid, teicoplanin, and vancomycin. No multi-resistant Enterococcus spp. were detected. A total of 12 ARGs were identified in Enterococcus spp., with the presence of at least 1 ARG in every isolate. The identified ARGs encoded resistance to aminoglycosides (aac(6')-I, ant(6)-Ia, aac(6')-Iih and spw), tetracyclines (tet(M), tet(L) and tet(S)), and macrolide-lincosamide-streptogramin AB (lnu(B,G), lsa(A,E), and msr(C)), and their presence was associated with phenotypical resistance. Core genome multilocus sequence typing (cgMLST) revealed the high diversity of E. faecalis and E. faecium isolates, even within the same geographical area. The distribution of resistant Enterococcus spp. in wild foxes in Latvia highlights the importance of a One Health approach in tackling AMR.

Half sandwich-type osmium, ruthenium, iridium and rhodium complexes with bidentate glycosyl heterocyclic ligands induce cytostasis in platinum-resistant ovarian cancer cells and bacteriostasis in Gram-positive multiresistant bacteria.

The toxicity of and resistance to platinum complexes as cisplatin, oxaliplatin or carboplatin calls for the replacement of these therapeutic agents in clinical settings. We have previously identified a set of half sandwich-type osmium, ruthenium and iridium complexes with bidentate glycosyl heterocyclic ligands exerting specific cytostatic activity on cancer cells but not on non-transformed primary cells. The apolar nature of the complexes, conferred by large, apolar benzoyl protective groups on the hydroxyl groups of the carbohydrate moiety, was the main molecular feature to induce cytostasis. We exchanged the benzoyl protective groups to straight chain alkanoyl groups with varying length (3 to 7 carbon units) that increased the IC50 value as compared to the benzoyl-protected complexes and rendered the complexes toxic. These results suggest a need for aromatic groups in the molecule. The pyridine moiety of the bidentate ligand was exchanged for a quinoline group to enlarge the apolar surface of the molecule. This modification decreased the IC50 value of the complexes. The complexes containing [(η6-p-cymene)Ru(II)], [(η6-p-cymene)Os(II)] or [(η5-Cp*)Ir(III)] were biologically active unlike the complex containing [(η5-Cp*)Rh(III)]. The complexes with cytostatic activity were active on ovarian cancer (A2780, ID8), pancreatic adenocarcinoma (Capan2), sarcoma (Saos) and lymphoma cell lines (L428), but not on primary dermal fibroblasts and their activity was dependent on reactive oxygen species production. Importantly, these complexes were cytostatic on cisplatin-resistant A2780 ovarian cancer cells with similar IC50 values as on cisplatin-sensitive A2780 cells. In addition, the quinoline-containing Ru and Os complexes and the short chain alkanoyl-modified complexes (C3 and C4) proved to be bacteriostatic in multiresistant Gram-positive Enterococcus and Staphylococcus aureus isolates. Hereby, we identified a set of complexes with submicromolar to low micromolar inhibitory constants against a wide range of cancer cells, including platinum resistant cells and against multiresistant Gram-positive bacteria.

Evaluation of antimicrobial susceptibility and genetic profiles (ERIC-PCR) of Enterococcus species, isolated from chicken viscera

The genus Enterococcus can be found in water, soil, and food, and above all, they are part of the animal (including human) intestinal microbiota. Food prevalence is mainly due to their resistance to adverse environmental conditions. Seventy-three isolates from chicken viscera were confirmed to belong to the Enterococcus genus by biochemical tests and carbohydrate fermentation. Phenotypic characterization of the species indicates that E. casseliflavus was the predominant specie. Antimicrobial resistance to amikacin (42 %), kanamycin (38 %), streptomycin (55 %), and erythromycin (33 %) in the isolates was notorious. The analysis obtained from ERIC-PCR profiles shows a high genetic variability among the isolates. In addition, a relationship between the antimicrobial and ERIC-PCR profiles was observed among isolates. These results indicate the presence of multi-resistant Enterococcus in commercial chicken viscera with high genetic variability, which could be a potential nosocomial bacterium or transfer this resistance to another pathogenic species causing human diseases.

Identification of a Novel Two-Peptide Lantibiotic from Vagococcus fluvialis.

ABSTRACTInfections caused by multiresistant pathogens have become a major problem in both human and veterinary medicine. Due to the declining efficacy of many antibiotics, new antimicrobials are needed. Promising alternatives or additions to antibiotics are bacteriocins, antimicrobial peptides of bacterial origin with activity against many pathogens, including antibiotic-resistant strains. From a sample of fermented maize, we isolated a Vagococcus fluvialis strain producing a bacteriocin with antimicrobial activity against multiresistant Enterococcus faecium. Whole-genome sequencing revealed the genes for a novel two-peptide lantibiotic. The production of the lantibiotic by the isolate was confirmed by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry, which revealed distinct peaks at 4,009.4 m/z and 3,181.7 m/z in separate fractions from reversed-phase chromatography. The combination of the two peptides resulted in a 1,200-fold increase in potency, confirming the two-peptide nature of the bacteriocin, named vagococcin T. The bacteriocin was demonstrated to kill sensitive cells by the formation of pores in the cell membrane, and its inhibition spectrum covers most Gram-positive bacteria, including multiresistant pathogens. To our knowledge, this is the first bacteriocin characterized from Vagococcus.IMPORTANCE Enterococci are common commensals in the intestines of humans and animals, but in recent years, they have been identified as one of the major causes of hospital-acquired infections due to their ability to quickly acquire virulence and antibiotic resistance determinants. Many hospital isolates are multiresistant, thereby making current therapeutic options critically limited. Novel antimicrobials or alternative therapeutic approaches are needed to overcome this global problem. Bacteriocins, natural ribosomally synthesized peptides produced by bacteria to eliminate other bacterial species living in a competitive environment, provide such an alternative. In this work, we purified and characterized a novel two-peptide lantibiotic produced by Vagococcus fluvialis LMGT 4216 isolated from fermented maize. The novel lantibiotic showed a broad spectrum of inhibition of Gram-positive strains, including vancomycin-resistant Enterococcus faecium, demonstrating its therapeutic potential.

Genomic islands mediate environmental adaptation and the spread of antibiotic resistance in multiresistant Enterococci - evidence from genomic sequences

BackgroundGenomic islands (GIs) play an important role in the chromosome diversity of Enterococcus. In the current study, we aimed to investigate the spread of GIs between Enterococcus strains and their correlation with antibiotic resistance genes (ARGs). Bitsliced Genomic Signature Indexes (BIGSI) were used to screen the NCBI Sequence Read Archive (SRA) for multiple resistant Enterococcus. A total of 37 pairs of raw reads were screened from 457,000 whole-genome sequences (WGS) in the SRA database, which come from 37 Enterococci distributed in eight countries. These raw reads were assembled for the prediction and analysis of GIs, ARGs, plasmids and prophages.ResultsThe results showed that GIs were universal in Enterococcus, with an average of 3.2 GIs in each strain. Network analysis showed that frequent genetic information exchanges mediated by GIs occurred between Enterococcus strains. Seven antibiotic-resistant genomic islands (ARGIs) were found to carry one to three ARGs, mdtG, tetM, dfrG, lnuG, and fexA, in six strains. These ARGIs were involved in the spread of antibiotic resistance in 45.9% of the 37 strains, although there was no significant positive correlation between the frequency of GI exchanges and the number of ARGs each strain harboured (r = 0. 287, p = 0.085). After comprehensively analysing the genome data, we found that partial GIs were associated with multiple mobile genetic elements (transposons, integrons, prophages and plasmids) and had potential natural transformation characteristics.ConclusionsAll of these results based on genomic sequencing suggest that GIs might mediate the acquisition of some ARGs and might be involved in the high genome plasticity of Enterococcus through transformation, transduction and conjugation, thus providing a fitness advantage for Enterococcus hosts under complex environmental factors.

Acute Ulcerative Enterocolitis With Severe Protein Loss Due to Mucosal Invasion With Enterococcus spp. in a Dog With Exocrine Pancreatic Insufficiency: A Case Report

We describe an unusual case of severe acute protein-losing enteropathy in a dog, which presented with a systemic inflammatory response syndrome. This dog's condition could not be categorized as any well-known canine intestinal condition. Instead, components of several enteropathies like acute hemorrhagic diarrhea syndrome (AHDS), chronic inflammatory enteropathy (CIE), and ulcerative and granulomatous colitis were present. Thorough investigations identified concurrent exocrine pancreatic insufficiency (EPI) and hypocobalaminemia. On histopathology, marked diffuse chronic-active ileitis and ulcerative colitis with fibroplasia and neovascularization were present. Intestinal biopsy cultures identified E.coli and multiresistant Enterococcus spp. The latter was identified as mucosally invasive using fluorescent in situ hybridization (FISH). Protracted clinical signs following the acute presentation required intensive care including enteral and parenteral feeding for a successful outcome, but eventually stabilized with antibiotics and immunosuppressive doses of glucocorticoids. This case highlights a potentially previously unrecognized condition, suspected to be a form of CIE manifesting acutely after bacterial mucosal invasion. In this case, this might have been facilitated by EPI-induced dysbiosis. The use of FISH and mucosal culture in this context provided important clinical information and should be considered more frequently in CIE and non-responsive AHDS.

N-Terminal guanidine derivatives of teicoplanin antibiotics strongly active against glycopeptide resistant Enterococcus faecium.

Antibiotic resistance is one of the major challenges in healthcare of our time. To meet this challenge, we designed and prepared guanidine and lipophilic guanidine derivatives of the glycopeptide antibiotic teicoplanin to armed them with activity against the most threatening nosocomial bacteria, multiresistant enterococci. From teicoplanin and its pseudoaglycone, a series of N-terminal guanidine derivatives have been prepared with free and amide C-terminal parts. Six aliphatic and aromatic lipophilic carbodiimides were prepared and used for the synthesis of lipophilic guanidine teicoplanin conjugates. All new N-terminal guanidine antibiotics showed high activity against a standard panel of Gram-positive bacteria. Four selected derivatives displayed excellent antibacterial activity against a series of nosocomial VanA Enterococcus faecium strains.

Identification of a poxtA- and cfr-carrying multiresistant Enterococcus hirae strain.

Identification of a poxtA- and cfr-carrying multiresistant Enterococcus hirae strain.

Antimicrobial and antibiofilm activity of the essential oil from dried leaves of Eucalyptus staigeriana

ABSTRACT: In recent years, compounds with biological properties produced by plants have received attention as an alternative to control microorganisms. Essential oils extracted from green leaves of Eucalyptus sp. have been demonstrated to have antimicrobial activities, but so far there are no reports of antimicrobial activity of essential oils extracted from dried leaves of Eucalyptus staigeriana. So, the objectives of this study were to determine the chemical composition of the essential oils obtained from dried leaves of E. staigeriana (EOdlES) and to evaluate in vitro antimicrobial and antibiofilm activities of EOdlES against gram-positive and gram-negative, resistance and multiresistant Enterococcus faecalis isolated from food and clinical samples. The characterization of EOdlES was performed by gas chromatography-mass spectrometry (GC/MS). For this study, 26 bacterial strains were used, which included 11 reference strains and 15 antibiotic resistant and multiresistant E. faecalis strains. Antimicrobial activities of EOdlES against gram-positive and gram-negative were determined using the disc diffusion method. The minimum inhibitory concentration (MIC) value was evaluated by a microbroth dilution technique. The antibiofilm effects were assessed by microtiter plate method. As a result, 21 compounds were identified, being oxygenated monoterpenes (69.58%) the major chemical family. EOdlES showed only antimicrobial activity against gram-positive strains. E. faecalis resistant and multiresistant strains show the lowest MIC (3.12 to 6.25%), when compared with reference E. faecalis strain. EOdlES has the ability to inhibit the biofilm formation, but little or none ability to inhibit the preformed biofilm. This study demonstrates that EOdlES is a promising alternative to control important foodborne and clinic gram-positive resistant bacteria.

Sepsis by Multiresistant Enterococci Diagnosed Based on Oral Manifestations

Sepsis by Multiresistant Enterococci Diagnosed Based on Oral Manifestations

The emergence of multi-resistant Enterococcus faecalis clonal complex, CC4, causing nosocomial infections.

Enterococcus faecalis is commonly found as a commensal gut bacteria, but some linages have caused increasing extra-gastrointestinal infections. In particular, strains with high-level virulence or antimicrobial resistance are prevalent in healthcare settings as nosocomial pathogens. This study was performed to elucidate the epidemiological characteristics and antimicrobial susceptibility profiles of E. faecalis causing nosocomial infections in a Chinese general hospital over a 4-year period. We collected 77 isolates causing extra-gastrointestinal infections from patients at 14 different wards in a tertiary hospital from 2011 to 2014. The population relationship was assessed by multilocus sequence typing and multilocus variable-number tandem repeat analysis. The Kirby-Bauer disk diffusion method was used to evaluate susceptibility against 11 antimicrobial agents. The isolates showed high-level resistance to tetracycline (86.5 %), erythromycin (78.4 %), rifampin (62.2 %), etc. The major clonal complexes (CCs) included CC4, CC16 and CC21. As the most dominant subtype, CC16 was identified in almost all of the wards and all types of samples, but the isolation rate decreased continually. In contrast, the isolation rates of CC4 and CC21 increased and the proportion of these two CCs in 2014 was more than three times that in 2011. In addition, CC4 showed higher resistance than CC16. This study demonstrated the prevalent subtypes and resistance profiles of E. faecalis causing nosocomial infection, and indicated that CC4 may be a newly emerging high-risk, multi-resistant cluster. More surveillance is urgently needed, which will increase our understanding of the prevention and treatment of such infections.

Evaluation of the antimicrobial activity of a blend of monoglycerides against Escherichia coli and Enterococci with multiple drug resistance.

Bacterial antibiotic resistance is a natural phenomenon, seriously affecting the treatment of infections. The biggest danger is that current antibiotics are not able to eradicate the resistant strains. In recent years, alternative antibacterial substances are being sought, which can help in these cases. Fatty acids and monoglycerides areknown among the natural substances for their antimicrobial properties and, important detail, bacteria do not develop resistance to them. In this work, we studied the antimicrobial effects of a monoglyceride blend against some multi-resistant Enterococci and Escherichia coli strains. Based on literature data, a blend of fatty acids and their monoglycerides was created and its antimicrobial activity was evaluated against 37 strains of E. coli and 17 Enterococci presenting resistance to at least two antibiotics. A different behavior was observed in the two groups of bacteria, proving that alternative substances can be considerate for the potential treatment of multidrug-resistant strains.

Intestinal carriage of vancomycin-resistant enterococci in a community setting in Casablanca, Morocco.

This study aimed to determine the rate of intestinal carriage of vancomycin-resistant enterococci (VRE) and to perform a phenotypic and genotypic characterisation of VRE isolates in the community in Casablanca, Morocco. During 6 months in 2014, 113 faecal samples were examined for the presence of enterococci. Antibiotic susceptibility of the isolates was determined by the disk diffusion method. Phenotypic and genotypic species identification was performed, and the vanA, vanB and vanC genes were detected by PCR. Each bacterial isolate resistant to vancomycin was subjected to amplification and sequencing of the 16S rRNA gene. In total, 100 strains were collected from a community population of 80 persons; 55% of the isolates were identified as Enterococcus faecium and 45% as Enterococcus faecalis. The resistance profile showed that 88% of the strains were multiresistant. The rate of faecal carriage of VRE was 21% (n=21), among which 8 strains were E. faecalis (17.8% of all E. faecalis) and 13 strains were E. faecium (23.6% of all E. faecium). PCR analysis revealed that all of the strains were resistant to vancomycin owing to possession of the vanA gene. The emergence of VRE and the high rate of colonisation by multiresistant enterococci are alarming. Strict measures are required to control the further spread of these strains in the Moroccan community.

Efficient Inactivation of Multi-Antibiotics Resistant Nosocomial Enterococci by Purified Hiracin Bacteriocin.

Because of the emergence of multi-antibiotic resistant bacteria, a number of infectious diseases have become a major concern to treat in health care services worldwide. This situation is worsened by the fact that very limited progress has been made in developing new and potent antibiotics in recent years. In this context antimicrobial peptides (AMPs) represent new potential therapeutic compounds with bactericidal or bacteriostatic activity against closely related bacterial strains. In this study, a collection of enterococci (n=170) from clinical sources were investigated for their potential to inhibit multiresistant nosocomial enterococci from Iranian hospitals. Four isolates produced antimicrobial peptides that inhibited all the antibiotic resistant enterococci. This included three Enterococcus faecium isolates producing combinations of enterocin A, B and L50 AB. The most potent antagonism was produced by E. faecalis HO91. Purification and subsequent characterization by MALDI-TOF MS, Edman degradation and DNA-sequencing revealed that the antimicrobial compound was Hiracin. The purified Hiracin was evaluated for antibacterial activity against 12 multiresistant enterococcal isolates from clinical samples. The results demonstrated that Hiracin is highly effective towards enterococci which were resistant even to antibiotics from four distinct classes. The present research addresses Hiracin as a promising alternative to conventional antibiotics in treatment of multiresistant enterococcal infections.

Virulence and antimicrobial resistance factors of Enterococcusspp. isolated from fecal samples from piggery farms in Eastern Cape, South Africa.

BackgroundEnterococci have emerged as an important opportunistic pathogen causing life-threatening infections in hospitals. The emergence of this pathogen is associated with a remarkable capacity to accumulate resistance to antimicrobials and multidrug-resistance particularly to vancomycin, erythromycin and streptomycin have become a major cause of concern for the infectious diseases community. In this paper, we report the prevalence of Enterococcus in respect to species distribution, their virulence and antibiogram profiles.MethodsFour hundred fecal samples were collected from two piggery farms in the Eastern Cape Province of South Africa. Enterococcus species were isolated and confirmed with generic specific primers targeting the tuf gene (encoding elongation factor). The confirmed isolates were speciated with enterococci species specific primers that aimed at delineating them into six species that are commonly associated with infections in humans. Antibiotic susceptibility testing was performed by disc diffusion method. Six virulence genes and antimicrobial resistance profiles of the isolates were evaluated molecularly.ResultsMolecular identification of the presumptive isolates confirmed 320 isolates as Enterococcus spp. Attempt at speciation of the isolates with primers specific for E. faecalis, E. durans, E. casseliflavus, E. hirae and E. faecium delineated them as follows: E. faecalis (12.5 %), E. hirae (31.25 %), E. durans (18.75 %) and E. faecium (37.5 %) while E. casseliflavus was not detected. All the isolates were resistant to vancomycin, streptomycin and cloxacillin, and to at least two different classes of antibiotics, with 300 (93.8 %) isolates being resistant to five or more antibiotics. Also, three out of the six virulence genes were detected in majority of the isolates and they are Adhesion of collagen in E. faecalis (ace) (96.88 %), gelatinase (gelE) (93.13 %) and surface protein (esp) (67.8 %).ConclusionThere was high prevalence of multi-resistant vancomycin Enterococcus spp. (VREs) in the fecal samples of pigs in the farms studied, and this poses health implications as vancomycin is an important drug in human medicine. Further studies are needed to determine the spread of vancomycin resistance among bacteria of human origin in the communities.

Effect of vancomycin on the proteome of the multiresistant Enterococcus faecium SU18 strain.

This study highlights the power of proteomics in the study of differential protein expression in a multiresistant Enterococcus faecium strain when subjected to vancomycin stress.

Vancomycin-resistant enterococci among haemodialysis patients in Portugal: Prevalence and molecular characterization of resistance, virulence and clonality

IntroductionVancomycin-resistant enterococci (VRE) among haemodialysis patients has increased rapidly and, to date, there is no report of this incidence in Portugal. MethodsA total of 121 faecal samples were collected from haemodialysis patients, and then tested for VRE. Antimicrobial resistance, virulence and multilocus sequence typing (MLST) were studied. ResultsVRE prevalence was 3.3%. Three VRE isolates, Enterococcus faecium, Enterococcus faecalis and Enterococcus raffinosus, were multi-resistant and vanA-positive. E. faecium and E. faecalis belonged to CC17 and CC2, respectively. ConclusionHaemodialysis patients in Portugal are colonized with virulent, multi-resistant enterococci from high-risk clonal complexes, representing a public health concern.

Deep coma and diffuse white matter abnormalities caused by sepsis-associated encephalopathy

In January, 2012, a 53-year-old woman with a history of progressive polyposis coli and hypertension was admitted to the intensive care unit (ICU) of our hospital because of septic shock 4 days after laparoscopic subtotal colectomy. She was intubated and mechanically ventilated, underwent emergent re-laparotomy for anastomotic leakage, and was treated with antibiotics. Blood cultures were positive for multiresistant Enterococcus faecium. After re-laparotomy the patient was sedated with midazolam for 2 days. The neurologist was consulted on the fourth postoperative day because of the patient’s persistent low level of consciousness. On neurological examination, we found no eye opening or motor response to a painful stimulus, intact brainstem refl exes, and generalised arefl exia of arms and legs with indiff erent plantar refl exes. We observed no signs indicative of minimally convulsive status epilepticus. During the period of septic shock and surgery, blood pressure had not been lower than 100/50 mm Hg and laboratory tests did not show abnormalities that could explain the patient’s coma. Non-contrast CT (NCCT) of the brain showed abnormal hypodensity of the complete white matter with swelling of the entire brain (fi gure); CT angiography was normal. Electromyography showed absence of motor unit potentials in arm and leg muscles without evidence for accompanying neuropathy. We made a diagnosis of sepsis-associated encephalopathy and critical illness myopathy. Because of the deep coma and the diff use and severely abnormal aspect of the white matter—both associated with poor outcome—dis continuation of treatment was discussed, but we recommended to continue treatment. On the ninth postoperative day the patient opened her eyes in response to painful stimuli, but there was still no motor response. Follow-up NCCT showed no improvement of the white matter abnormalities. In the following weeks the condition of the patient gradually improved and 4 weeks after the re-laparotomy she had regained full consciousness. When the patient was discharged from the ICU her muscle strength had gradually improved with movements against gravity now possible. At that time brain MRI was normal except for a small number of white matter lesions (fi gure). The patient was transferred to a rehabilitation centre 6 weeks after the initial onset of septic shock. At that point she was able to walk short distances. At last follow-up on Aug 19, 2012, she had regained independence in activities of daily living and was living at home. Sepsis-associated encephalopathy is a severe complication of sepsis and is associated with poor outcome. The reported incidence ranges from 9% to 71% because of variations in the defi nition. A recent study in an ICU showed that patients with sepsis secondary to intestinal infections are prone to develop septic encephalopathy, with Escherichia coli and Enterococcus faecium among the most frequently cultured bacteria. The exact pathogenesis of sepsis-associated encephalopathy remains unclear; disruption of the blood-brain barrier and mitochondrial dysfunction are probably involved. Imaging of the brain can show atrophy and periventricular white matter lesions. The diff use and severe white matter abnormalities like those we observed in our patient are rare and have been associated with poor outcome. This case shows that severe encephalopathy with extensive white matter lesions can be a reversible condition. Clinicians should realise that the fi rst signs of improvement of the clinical condition could still be observed beyond 7 days after onset.