In vitro and in vivo efficacy of zinc oxide green nanoparticles against multidrug-resistant Salmonella Typhi.

Antibiotic resistance is an increasing threat, requiring novel therapeutic solutions. Metal nanoparticles e.g., zinc oxide nanoparticles (ZnO NPs) exhibited the potential against many bacterial pathogens. Strains of Salmonella enterica serovar Typhi resistant to ceftriaxone were reported first from Pakistan in 2016. Since then, S. Typhi is a pathogen of concern globally owing to its rapidly emerging resistance potential against many last resort antibiotics. In the present study, in vitro and in vivo antimicrobial activity of ZnO NPs against multidrug resistant (MDR) and extensively drug resistant (XDR) Salmonella Typhi strains from Pakistan was evaluated. Zinc oxide green nanoparticles (ZnO GNPs), synthesized from Aloe vera, were characterized by SEM, XRD, UV-vis and Raman spectroscopy. In vitro antibacterial activity of two different concentrations of ZnO GNPs (7 and 15%) was checked using agar well diffusion method. Further, broth microdilution and time kill assays were performed using the ZnO GNPs. In vivo assays were conducted in BALB/c mice sepsis models. In all the three methods, agar well diffusion assay broth microdilution and time kill assay, different zinc oxide dihydrate precursor concentrations had shown the antibacterial activity. The minimum inhibitory concentration (MIC) of ZnO GNPs nanoparticles against MDR and XDR S. Typhi strains was found as 16 to 64 µg/ml. In vivo experiment has shown a significant decrease in CFU/ml in the mice treated with ZnO GNPs as compared to the control group. Our findings have revealed that ZnO GNPs have significant antibacterial activity against MDR and XDR S. Typhi, both in vitro and in vivo.

Biomimetic Metal-Organic Framework Gated Nanoplatform for Sonodynamic Therapy against Extensively Drug Resistant Bacterial Lung Infection.

Novel antimicrobial strategies are urgently needed to treat extensively drug-resistant (XDR) bacterial infections due to the high mortality rate and lack of effective therapeutic agents. Herein, nanoengineered human umbilical cord mesenchymal stem cells (hUC-MSCs), named PMZMU, are designed as a sonosensitizer for synergistic sonodynamic-nano-antimicrobial therapy against gram-negative XDR bacteria. PMZMU is composed of a bacterial targeting peptide (UBI29-41) modified hUC-MSCs membrane (MSCm), a sonosensitizer meso-tetra(4-car-boxyphenyl) porphine doped mesoporous organo-silica nanoparticle and an acidity-responsive metal-organic framework ZIF-8. This innovative formulation enables efficient loading of polymyxin B, reduces off-target drug release, increases circulation and targeting efficacy, and generates reactive oxygen species upon ultrasound irradiation. PMZMU exhibits remarkable in vitro inhibitory activity against four XDR bacteria: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa (PA), and Escherichia coli. Taking advantage of the bacterial targeting ability of UBI29-41 and the inflammatory chemotaxis of hUC-MSC, PMZMU can be precisely delivered to lung infection sites thereby augmenting polymyxin B concentration. PMZMU-mediated sonodynamic therapy significantly reduces bacterial burden, relieves inflammatory damage by promoting the polarization of macrophages toward M2 phenotype, and improves survival rates without introducing adverse events. Overall, this study offers promising strategies for treating deep-tissue XDR bacterial infections, and guides the design and optimization of biomimetic nanomedicine.

Antibacterial Activities of Phenolic Compounds in Miang Extract: Growth Inhibition and Change in Protein Expression of Extensively Drug-Resistant Klebsiella pneumoniae.

The rising incidence of extensively drug-resistant (XDR) Klebsiella pneumoniae, including carbapenem- and colistin-resistant strains, leads to the limitation of available effective antibiotics. Miang, known as chewing tea, is produced from Camellia sinensis var. assamica or Assam tea leaves fermentation. Previous studies revealed that the extract of Miang contains various phenolic and flavonoid compounds with numerous biological activities including antibacterial activity. However, the antibacterial activity of Miang against XDR bacteria especially colistin-resistant strains had not been investigated. In this study, the compositions of phenolic and flavonoid compounds in fresh, steamed, and fermented Assam tea leaves were examined by HPLC, and their antibacterial activities were evaluated by the determination of the MIC and MBC. Pyrogallol was detected only in the extract from Miang and showed the highest activities with an MIC of 0.25 mg/mL and an MBC of 0.25-0.5 mg/mL against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli ATCC 25922, colistin-resistant E. coli, and colistin-resistant K. pneumoniae. The effects on morphology and proteomic changes in K. pneumoniae NH54 treated with Miang extract were characterized by SEM and label-free quantitative shotgun proteomics analysis. The results revealed that Miang extract caused the decrease in bacterial cell wall integrity and cell lysis. The up- and downregulated expression with approximately a 2 to >5-fold change in proteins involved in peptidoglycan synthesis and outer membrane, carbohydrate, and amino acid metabolism were identified. These findings suggested that Miang containing pyrogallol and other secondary metabolites from fermentation has potential as an alternative candidate with an antibacterial agent or natural active pharmaceutical ingredient against XDR bacteria including colistin-resistant bacteria.

A predictive score for the result of carbapenem-resistant Enterobacterales and vancomycin-resistant enterococci screening.

BACKGROUND: The duration of extensively drug-resistant bacteria (XDR) carriage depends on several factors for which the information can be difficult to recover. AIM: To determine whether past screening and clinical results of patients can predict the results of subsequent screening. METHODS: In total, 256 patients were retrospectively included from 10 healthcare centres in France from January 2014 to January 2022. We created a predictive clearance score, ranging from -5 to +7, that included the number of XDR species and the type of resistance detected in the sample, as well as the time from the last positive sample, the number of previous consecutive negative samples, and obtaining at least one negative PCR result in the collection. This score could be used for the upcoming rectal screening of a patient carrying an XDR as soon as the last screening sample was negative. FINDINGS: The negative predictive value was >99% for score ≤0. The median time to achieve XDR clearance was significantly shorter for a score of 0 (443 days (259-705)) than that based on previously published criteria. CONCLUSION: This predictive score shows high performance for the assessment of XDR clearance. Relative to previous guidelines, it could help to lift specific infection prevention and control measures earlier. Nevertheless, the decision should be made according to other factors, such as antimicrobial use and adherence to hand hygiene.

Six Extensively Drug-Resistant Bacteria in an Injured Soldier, Ukraine.

Blood and surveillance cultures from an injured service member from Ukraine grew Acinetobacter baumannii, Klebsiella pneumoniae, Enterococcus faecium, and 3 distinct Pseudomonas aeruginosa strains. Isolates were nonsusceptible to most antibiotics and carried an array of antibiotic resistant genes, including carbapenemases (blaIMP-1, blaNDM-1, blaOXA-23, blaOXA-48, blaOXA-72) and 16S methyltransferases (armA and rmtB4).

Identification of Bacterial Membrane Selectivity of Romo1-Derived Antimicrobial Peptide AMPR-22 via Molecular Dynamics.

The abuse or misuse of antibiotics has caused the emergence of extensively drug-resistant (XDR) bacteria, rendering most antibiotics ineffective and increasing the mortality rate of patients with bacteremia or sepsis. Antimicrobial peptides (AMPs) are proposed to overcome this problem; however, many AMPs have attenuated antimicrobial activities with hemolytic toxicity in blood. Recently, AMPR-11 and its optimized derivative, AMPR-22, were reported to be potential candidates for the treatment of sepsis with a broad spectrum of antimicrobial activity and low hemolytic toxicity. Here, we performed molecular dynamics (MD) simulations to clarify the mechanism of lower hemolytic toxicity and higher efficacy of AMPR-22 at an atomic level. We found four polar residues in AMPR-11 bound to a model mimicking the bacterial inner/outer membranes preferentially over eukaryotic plasma membrane. AMPR-22 whose polar residues were replaced by lysine showed a 2-fold enhanced binding affinity to the bacterial membrane by interacting with bacterial specific lipids (lipid A or cardiolipin) via hydrogen bonds. The MD simulations were confirmed experimentally in models that partially mimic bacteremia conditions in vitro and ex vivo. The present study demonstrates why AMPR-22 showed low hemolytic toxicity and this approach using an MD simulation would be helpful in the development of AMPs.

In Vitro Screening of a 1280 FDA-Approved Drugs Library against Multidrug-Resistant and Extensively Drug-Resistant Bacteria.

Alternative strategies against multidrug-resistant (MDR) bacterial infections are suggested to clinicians, such as drug repurposing, which uses rapidly available and marketed drugs. We gathered a collection of MDR bacteria from our hospital and performed a phenotypic high-throughput screening with a 1280 FDA-approved drug library. We used two Gram positive (Enterococcus faecium P5014 and Staphylococcus aureus P1943) and six Gram negative (Acinetobacter baumannii P1887, Klebsiella pneumoniae P9495, Pseudomonas aeruginosa P6540, Burkholderia multivorans P6539, Pandoraea nosoerga P8103, and Escherichia coli DSM105182 as the reference and control strain). The selected MDR strain panel carried resistance genes or displayed phenotypic resistance to last-line therapies such as carbapenems, vancomycin, or colistin. A total of 107 compounds from nine therapeutic classes inhibited >90% of the growth of the selected Gram negative and Gram positive bacteria at a drug concentration set at 10 µmol/L, and 7.5% were anticancer drugs. The common hit was the antiseptic chlorhexidine. The activity of niclosamide, carmofur, and auranofin was found against the selected methicillin-resistant S. aureus. Zidovudine was effective against colistin-resistant E. coli and carbapenem-resistant K. pneumoniae. Trifluridine, an antiviral, was effective against E. faecium. Deferoxamine mesylate inhibited the growth of XDR P. nosoerga. Drug repurposing by an in vitro screening of a drug library is a promising approach to identify effective drugs for specific bacteria.

Retrospective 8-Year Study on the Antibiotic Resistance of Uropathogens in Children Hospitalised for Urinary Tract Infection in the Emilia-Romagna Region, Italy.

The development and spread of antibiotic resistance is an increasingly important global public health problem, even in paediatric urinary tract infection (UTI). In light of the variability in the data, it is necessary to conduct surveillance studies to determine the prevalence of antibiotic resistance in specific geographical areas to optimize therapeutic management. In this observational, retrospective, multicentre study, the medical records of 1801 paediatric patients who were hospitalised for UTI between 1 January 2012, and 30 June 2020, in Emilia-Romagna, Italy, were analysed. Escherichia coli was the most frequently detected pathogen (75.6%), followed by Klebsiella pneumoniae (6.9%) and Pseudomonas aeruginosa (2.5%). Overall, 840 cases (46.7%) were due to antimicrobial-resistant uropathogens: 83 (4.7%) extended spectrum beta-lactamase (ESBL)-producing, 119 (6.7%) multidrug resistant (MDR) and 4 (0.2%) extensively drug resistant (XDR) bacteria. Empirical antibiotic therapy failed in 172 cases (9.6%). Having ESBL or MDR/XDR uropathogens, a history of recurrent UTI, antibiotic therapy in the preceding 30 days, and empirical treatment with amoxicillin or amoxicillin/clavulanate were significantly associated with treatment failure, whereas first-line therapy with third-generation cephalosporins was associated with protection against negative outcomes. In conclusion, the increase in the resistance of uropathogens to commonly used antibiotics requires continuous monitoring, and recommendations for antibiotic choice need updating. In our epidemiological context, amoxicillin/clavulanate no longer seems to be the appropriate first-line therapy for children hospitalised for UTI, whereas third-generation cephalosporins continue to be useful. To further limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be implemented.

Fatal Pandoraea nosoerga infection after combined liver-lung transplantation for cystic fibrosis: a recontamination by the pre-transplantation strain.

A 26-year-old girl with a longstanding colonization by Pandoraea nosoerga underwent liver-lung transplantation for cystic fibrosis (CF) in 2018. Her brother also suffering from CF was also colonized by P. nosoerga. Despite appropriate perioperative antibiotic therapy, she had post-transplant bacteremic pneumonia caused by extensively drug-resistant P. nosoerga. Drug repurposing was used to optimize treatment options. The cause of post-transplant contamination was studied by comparative whole-genome sequencing including pre- and post-transplant strains and her brother's strains. Post-transplant contamination appeared to be due to her own pre-transplant strain, emphasizing the urgent need to study and implement effective decontamination protocols before transplantation.

Multidrug-Resistant and Extensively Drug-Resistant Enterobacteriaceae: Prevalence, Treatments, and Outcomes - A Retrospective Cohort Study.

BACKGROUND: Drug-resistant gram-negative bacteria (GNB) are a global public health threat, especially in intensive care units (ICU). This study explored the prevalence of drug-resistant Enterobacteriaceae infections in an ICU in Saudi Arabia. The appropriateness of the antibiotic therapies used and their ability to improve the clinical outcomes were also assessed. METHODS: A retrospective study was conducted from 2015 to 2018 in the different ICUs of a tertiary-care hospital in Saudi Arabia. Positive cultures for multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) Enterobacteriaceae, including Klebsiella pneumoniae, Escherichia coli, and Enterobacter sp., were included. The primary outcomes involved microbiological cure and 30 days in-hospital mortality rate, while the secondary outcome included the length of hospital stay (LOS). Regression models were used to assess the relationship between appropriateness of the antibiotic therapy and clinical outcomes. RESULTS: Of the 227 Enterobacteriaceae cultures included in this study, 60% were either MDR (n= 130) or XDR (n= 8) infections; no PDR Enterobacteriaceae cultures were identified. Majority of the patients were female (54%), and the average age was 60.1 ± 17.7 years. MDR/XDR cultures primarily comprised E. coli (51.4%), followed by K. pneumoniae (33%) and Enterobacter sp. (16%). Most commonly used antibiotics were piperacillin/tazobactam (53%), carbapenems (47%), and cephalosporins (21.3%). Antibiotic therapy was considered appropriate in only 85 of 138 (61.59%) patients. Microbiological cure rate was achieved in 40% of the cases, and in-hospital death rate was 84%. The average LOS was 27 days. Appropriateness of the antibiotic therapy prescribed could not predict any of the study outcomes. CONCLUSION: The study revealed a high prevalence of drug-resistant Enterobacteriaceae infections, which were associated with a high mortality rate. Therefore, it is essential to assess the effectiveness of antimicrobial stewardship program and infection prevention and control practices, particularly in critically ill patients.

Clinical outcomes of ceftazidime-avibactam in lung transplant recipients with infections caused by extensively drug-resistant gram-negative bacilli.

BACKGROUND: Infections produced by extensively drug-resistant (XDR) gram-negative bacilli (GNB) in solid organ transplant (SOT) are an important cause of morbidity and mortality. Ceftazidime/avibactam (CAZ-AVI) is a novel ß-lactam/ß-lactamase combination antibiotic with anti-GNB activity, but experience in real clinical practice with CAZ-AVI in lung transplant (LT) recipients is limited. METHODS: We conducted a retrospective study of patients with XDR-GNB infection who received at least 3 days of CAZ-AVI in the Department of Lung Transplantation Between December 2017 and December 2018 at China-Japan friendship hospital (CJFH). The general information, clinical manifestations, laboratory examinations, treatment course, and outcomes were summarized. RESULTS: A total of 10 patients who underwent LT at our center were included. They were all males with a mean age 51 years. Infections after LT included pneumonia and/or tracheobronchitis [n=9; 90% (9/10)], cholecystitis and blood stream infection (BSI) (n=1, patient 8). In these 10 LT recipients, the incidence of various airway complications was 70% (7/10). Carbapenem-resistant Klebsialla pneumoniae (CRKP) was the predominant pathogen, being detected in 9 patients. Multilocus sequence typing (MLST) analysis showed that all 9 CRKP isolates belonged to ST11. Six patients (6/10, 60%) started CAZ-AVI as salvage therapy after a first-line treatment with other antimicrobials. CAZ-AVI was administered as monotherapy or in combination regimens in 20% (2/10) and 80% (8/10) of patients respectively. There were no difference in temperature before and after CAZ-AVI treatment (P>0.05). White blood cell (WBC) at 7 days, and procalcitonin (PCT) at 7 days and 14 days significantly dropped (P<0.05). After 7-14 days of CAZ-AVI treatment, the PaO2/FiO2ratio (P/F ratio) significantly improved (P<0.05). Nine patients (9/10, 90%) obtained negative microbiologic culture of CRKP/CRPA, with a median time to was 6.7 days (range, 1-15 days). However, 5 patients (5/10, 50%) had relapse of CRKP/CRPA infections in the respiratory tract regardless of whether negative microbiologic culture was obtained or not. The 30-day survival rate was 100%, and the 90-day survival rate was 90% (1/10). No severe adverse events related to CAZ-AVI occurred. CONCLUSIONS: CAZ-AVI treatment of CRKP/ CRPA infection in LT recipients was associated with high rates of clinical success, survival, and safety, but recurrent CRKP/CRPA infections in the respiratory tract did occur.

Emerging extensively drug-resistant bacteria (eXDR) in France in 2018.

OBJECTIVE: This 2018 report of Healthcare-Associated Infections Early Warning and Response System (HAI-EWRS) notifications of carbapenemase-producing Enterobacteriaceae (CPE) or glycopeptide-resistant Enterococcus faecium (GRE), and of strains analysed by the National Reference Center for anti-microbial resistance (NRC) aimed to describe the epidemiology of emerging extensively drug-resistant bacteria (eXDR) in France and control measures implemented in hospital settings. PATIENTS AND METHODS: All HAI-EWRS notifications of eXDR received at the national level and all eXDR strains received at the NRC between January 1, 2018 and January 31, 2018 were analysed. Variables analysed were number of cases, number of strains, resistance mechanism, sample type, link with a foreign country, and control measures implemented. RESULTS: In 2018, 1704 CPE notifications and 315 GRE notifications were reported in France, with an increasing trend since 2012 (×6 for CPE, ×3 for GRE), from respectively 364 and 155 hospitals (+66% for CPE, +57% for GRE since 2012). eXDR strains were mainly isolated from rectal screening swabs. Notifications with patients receiving standard precautions were more often associated with outbreaks than notifications with patients receiving contact precautions at admission. NRC received 2674 CPE strains and 775 GRE strains in 2018 (×8.3 and ×2.8 compared with 2012). CONCLUSION: The increasing annual number of eXDR notifications and eXDR strains received by the NRC is multifactorial but reflects a worrying spread of eXDR in France. The number of infections remains low, but this article shows that existing recommendations are not fully implemented.

Asymptomatic carriage of extensively drug-resistant bacteria (eXDR), a simple way to assess spontaneous clearance.

The duration of eXDR carriage depends on several factors that might be difficult to recover. We aim to assess the duration of eXDR carriage by using a simple to recover parameter: the number of consecutive negative screening. 131 eXDR carriers (51 VRE and 80 CPE) were included. The number of consecutive negative screenings was strongly associated with eXDR clearance. All patients displaying at least three negative screenings over a seven-month period were never screened positive thereafter. Taking into account the number of negative screenings as a part of a case-by-case risk assessment would be helpful for the decision to maintain or lift eXDR-focused precautions.

Clinical, immunological and bacteriological characteristics of H7N9 patients nosocomially co-infected by Acinetobacter Baumannii: a case control study.

BACKGROUND: Bacterial co-infection of patients suffering from influenza pneumonia is a key element that increases morbidity and mortality. The occurrence of Acinetobacter baumannii co-infection in patients with avian influenza A (H7N9) virus infection has been described as one of the most prevalent bacterial co-infections. However, the clinical and laboratory features of this entity of H7N9 and A. baumannii co-infection have not been systematically investigated. METHODS: We collected clinical and laboratory data from laboratory-confirmed H7N9 cases co-infected by A. baumannii. H7N9 patients without bacterial co-infection and patients with A. baumannii-related pneumonia in the same hospital during the same period were recruited as controls. The antibiotic resistance features and the corresponding genome determinants of A. baumannii and the immune responses of the patients were tested through the respiratory and peripheral blood specimens. RESULTS: Invasive mechanical ventilation was the most significant risk factor for the nosocomial A. baumannii co-infection in H7N9 patients. The co-infection resulted in severe clinical manifestation which was associated with the dysregulation of immune responses including deranged T-cell counts, antigen-specific T-cell responses and plasma cytokines. The emergence of genome variations of extensively drug-resistant A. baumannii associated with acquired polymyxin resistance contributed to the fatal outcome of a co-infected patient. CONCLUSIONS: The co-infection of H7N9 patients by extensively drug-resistant A. baumannii with H7N9 infection is an important issue which deserves attention. The dysfunctions of immune responses were associated with the co-infection and were correlated with the disease severity. These data provide useful reference for the diagnosis and treatment of H7N9 infection.

Detection and characterization of a clinical Escherichia coli ST3204 strain coproducing NDM-16 and MCR-1.

OBJECTIVES: A plasmid-mediated colistin resistance gene, mcr-1, has been reported worldwide and has caused concern regarding a major therapeutic challenge. Alarmingly, mcr-1 has spread into clinical carbapenem-resistant Enterobacteriaceae isolates, resulting in extensively drug-resistant and even pan drug-resistant isolates that can cause untreatable infections. In this study, we report isolation of an extensively drug-resistant Escherichia coli strain EC1188 that coproduces NDM-16 and MCR-1 from a urine sample taken from a patient with craniocerebral injury. MATERIALS AND METHODS: E. coli strain EC1188 was identified and subjected to genotyping, susceptibility testing and conjugation experiments. The genetic locations of blaNDM-16 and mcr-1 were established with southern blot hybridization. The complete genome sequence of this strain was obtained and the genetic characteristics of the mcr-1- and blaNDM-16-harboring plasmids were analyzed. In addition, comparative genetic analyses of mcr-1 and blaNDM-16 with closely related plasmids were also carried out. RESULTS: Whole-genome sequencing revealed that strain EC1188 possess various resistance genes and virulence genes. S1-pulsed-field gel electrophoresis and southern blot suggested that the blaNDM-16 and mcr-1 genes were located on an ~65 kb plasmid and an ~80 kb plasmid, respectively. Moreover, the two genes could successfully transfer their resistance phenotype to E. coli strain C600. Sequence analysis showed that these two plasmids possessed high sequence similarity to previously reported blaNDM-5-harboring and mcr-1-harboring plasmids in China. CONCLUSION: To the best of our knowledge, this is the first report to isolate an E. coli strain that coproduces NDM-16 and MCR-1. In addition, we characterized the blaNDM-16-harboring plasmid for the first time. Our study further emphasizes that the co-occurrence of the two prevalent transferrable resistance plasmids in a single isolate is highly significant because infections caused by MCR-1-producing carbapenem-resistant Enterobacteriaceae isolates are increasing each year. It is imperative to perform active surveillance to prevent further dissemination of MCR-1-producing CRE isolates.

Efficiency of different control measures for preventing carbapenemase-producing enterobacteria and glycopeptide-resistant Enterococcus faecium outbreaks: a 6-year prospective study in a French multihospital institution, January 2010 to December 2015.

An infection control programme was implemented in a 21,000-bed multihospital institution for controlling the spread of carbapenemase-producing Enterobacteriaceae (CPE) and glycopeptide-resistant Enterococcus faecium (GRE), classified as 'emergent extensively drug-resistant bacteria' (eXDR) in France. We evaluated factors associated with outbreaks occurrence (n = 103), which followed 901 eXDR introductions (index case followed or not by secondary cases) from 2010 to 2015. In univariate analysis, knowing that patients had been hospitalised abroad, bacterial species (GRE vs CPE, as well as the CPE Klebsiella pneumoniae compared with the other Enterobacteriaceae species) and type of measures implemented within the first 2 days of hospitalisation were associated with outbreaks occurrence, but not the type of wards where carriers were hospitalised, nor the eXDR colonisation or infection status. In multivariate analysis, occurrence of outbreaks was significantly lower when contact precautions (odds ratio (OR): 0.34; 95% confidence interval (CI): 0.22-0.54) and even more when dedicated nursing staff (OR: 0.09; 95% CI: 0.02-0.39) were implemented around eXDR index cases within the first 2 days of hospitalisation (p < 10 - 3). GRE introductions were more frequently associated with occurrence of outbreaks than CPE (OR: 3.58; 95% CI: 2.32-5.51, p < 10 - 3). A sustained and coordinated strategy is efficient to limit the spread of eXDR at the scale of a large health institution.

Surveillance of antimicrobial resistance in Peking Union Medical College Hospital in 2017 / 中国感染与化疗杂志

Objective To investigate the antimicrobial resistance of clinical bacterial isolates in Peking Union Medical College Hospital (PUMCH) in 2017. Methods A total of 9 515 non-duplicate clinical isolates were collected from January 1 to December 31, 2017. Disc diffusion test (Kirby-Bauer method) and E-test method were employed to determine antimicrobial susceptibility. Results Gram-negative bacilli and gram-positive cocci accounted for 68.2％ and 31.8％, respectively among the 9 515 clinical isolates. Methicillin-resistant strains in S. aureus (MRSA) and coagulase-negative Staphylococcus (MRCNS) accounted for 25.6％ and 73.3％, respectively. Extended-spectrum β-lactamases (ESBLs) -producing strains accounted for 47.6％ (877/1 842), 27.6％ (335/1 213) and 33.0％ (59/179) in E. coli, Klebsiella spp (K. pneumoniae and K. oxytoca) and P. mirabilis, respectively. Enterbacteriaceae strains were still highly susceptible to carbapenems, with an overall resistance rate of ≤ 3.8％. The resistance rates of K. pneumoniae to imipenem and meropenem were 8.5％ and 8.2％, respectively. About 72.7％ and 70.4％ of A. baumannii isolateswere resistant to imipenem and meropenem. The resistance rate of P. aeruginosa to imipenem and meropenem was 14.8％ and 10.0％, respectively. The prevalence of extensively drug-resistant strains in A. baumannii, P. aeruginosa and K. pneumoniae was 31.7％ (239/753), 1.0％ (10/1 035), and 3.0％ (33/1 117), respectively. Conclusions The common bacterialisolates show various level of resistance to antimicrobial agents. Laboratory staff should improve communication with clinicians to prevent the spread of resistant strains.

Extensively drug-resistant bacteria: Which ethical issues?

OBJECTIVE: The increased bacterial resistance to antibiotics has now become a public health concern. How can we preserve the well-being of patients presenting with infections caused by extensively drug-resistant bacteria (EDRBs) and that of their contacts without inducing any loss of chance of survival, all the while living together and controlling the spread of these EDRBs? METHOD: Terre d'éthique, a French territorial ethics committee, was asked to reflect on this topic by the infection control unit of a French University Hospital as it raises many ethical issues. RESULTS: Patients are at the core of any ethical approach, and respecting their autonomy is fundamental. Patients should be adequately informed to be able to give consent. Indeed, the creation and dissemination of a register (list of names of contacts or infected patients) entails responsibility of the infected person and that of the community. This responsibility leads to an ethical dilemma as protecting the group (the whole population) necessarily means limiting individual freedom. The principle of autonomy should thus be compared with that of solidarity. Is medical confidentiality an obstacle to the sharing of information or lists of names? CONCLUSION: We did not aim to answer our problematic but merely wanted to show the complexity of EDRB spread in a broader societal and economic context, all the while respecting the rights of patients.

Extensively drug-resistant bacteria are an independent predictive factor of mortality in 130 patients with spontaneous bacterial peritonitis or spontaneous bacteremia.

AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis. METHODS: We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm(3). In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed. RESULTS: Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Enterococcus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeruginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95%CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95%CI: 1.024-1.236, P = 0.015) and INR (HR =1.553, 95%CI: 1.106-2.180, P = 0.011). CONCLUSION: XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.