colistin and Enterobacteriaceae-Infections

Several recent cases associating cleaned and high-level disinfected duodenoscopes with outbreaks of carbapenem-resistant Enterobacteriaceae (CRE) and related multidrug-resistant organisms (MDROs) may cause bronchoscopists, pulmonologists, and other stakeholders to inquire about the effectiveness of today's practices for reprocessing flexible bronchoscopes. The primary objectives of this study were to address this question and investigate the risk of bronchoscopes transmitting infections of CRE and related MDROs. The published literature and the US Food and Drug Administration's medical device database of adverse events were searched beginning in 2012, when endoscopy first emerged as a recognized risk factor for transmission of CRE. The Internet was also searched during this same time frame to identify other relevant cases. Several cases associating reprocessed bronchoscopes with infections of CRE or a related MDRO were identified. This study's findings suggest that bronchoscopes may pose an underrecognized potential for transmission of CRE and related MDROs, warranting greater public awareness, enhanced preventive measures, and updated reprocessing guidance. This study's data also suggest that the cleaning and high-level disinfection of bronchoscopes performed in accordance with published guidelines and manufacturer instructions may not always be sufficiently effective to eliminate this risk. Several factors were identified that can adversely affect a bronchoscope's reprocessing and pose a risk of transmission of these multidrug-resistant bacteria, including use of a damaged or inadequately serviced bronchoscope, and formation of an inaccessible biofilm. Recommendations are provided to improve the safety of flexible bronchoscopes, including supplementing their reprocessing with an enhanced measure such as sterilization when warranted, and strict adherence to a periodic servicing and maintenance schedule consistent with the bronchoscope manufacturer's instructions.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Bronchoscopes; Bronchoscopy; Carbapenem-Resistant Enterobacteriaceae; Colistin; Cross Infection; Disinfection; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Equipment Contamination; Equipment Reuse; Humans; Klebsiella Infections; Klebsiella pneumoniae; Pseudomonas aeruginosa; Pseudomonas Infections

The incidence of healthcare-associated multidrug resistant bacterial infections, particularly due to carbapenem resistant organisms, has been on the rise globally. Among these are the carbapenem resistant Acinetobacter baumannii and Enterobacteriaceae, which have been responsible for numerous outbreaks in neonatal units. The polymyxins (colistin and polymyxin B) are considered to be the last resort antibiotics for treating such infections. However, pharmacokinetic and pharmacodynamic data on the use of polymyxins in neonates and children are very limited, and there are safety concerns.. In this review, the authors summarize the global burden of multidrug resistance, particularly carbapenem resistance, in the neonatal and paediatric population, and the potential wider use of polymyxins in treating these infections.. Both colistin and polymyxin B have similar efficacy in treating multidrug resistant infections but have safety concerns. However, polymyxin B appears to be a better therapeutic option, with more rapid and higher steady state concentrations achieved compared to colistin and less reported nephrotoxicity. There is virtually no data in neonates and children currently; there is therefore an urgent need for pharmacokinetic and safety trials in these populations to determine the optimal drug and dosing regimens and provide recommendations for their use against carbapenem resistant infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Carbapenems; Child; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Humans; Infant, Newborn; Polymyxin B; Polymyxins

Multi-drug resistance in Gram negative bacteria, particularly in Enterobacteriaceae, is a major clinical and public health challenge. The main mechanism of resistance in Enterobacteriaceae is linked to the production of beta-lactamase hydrolysing enzymes such as extended spectrum beta-lactamases (ESBL), AmpC beta-lactamases and carbapenemases (Carbapenemase Producing Enterobacteriaceae (CPE)). ESBL and CPE resistance genes are located on plasmids, which can be transmitted between Enterobacteriaceae, facilitating their spread in hospitals and communities. These plasmids usually harbour multiple additional co-resistance genes, including to trimethoprim-sulfamethoxazole, aminoglycosides, and fluoroquinolones, making these infections challenging to treat. Asymptomatic carriage in healthy children as well as community acquired infections are increasingly reported, particularly with ESBL. Therapeutic options are limited and previously little used antimicrobials such as fosfomycin and colistin have been re-introduced in clinical practice. Paediatric experience with these agents is limited hence there is a need to further examine their clinical efficacy, dosage and toxicity in children. Antimicrobial stewardship along with strict infection prevention and control practices need to be adopted widely in order to preserve currently available antimicrobials. The future development of novel agents effective against beta-lactamases producers and their applicability in children is urgently needed to address the challenge of multi-resistant Gram negative infections.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Child; Colistin; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Plasmids

Colistin, a cationic polypeptide antibiotic, has reappeared in human medicine as a last-line treatment option for multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin is widely used in veterinary medicine for the treatment of gastrointestinal infections caused by Enterobacteriaceae. GNB resistant to colistin owing to chromosomal mutations have already been reported both in human and veterinary medicine, however several recent studies have just identified a plasmid-mediated mcr-1 gene encoding for colistin resistance in Escherichia coli colistin resistance. The discovery of a non-chromosomal mechanism of colistin resistance in E. coli has led to strong reactions in the scientific community and to concern among physicians and veterinarians. Colistin use in food animals and particularly in pig production has been singled out as responsible for the emergence of colistin resistance. The present review will focus mainly on the possible link between colistin use in pigs and the spread of colistin resistance in Enterobacteriaceae. First we demonstrate a possible link between Enterobacteriaceae resistance emergence and oral colistin pharmacokinetics/pharmacodynamics and its administration modalities in pigs. We then discuss the potential impact of colistin use in pigs on public health with respect to resistance. We believe that colistin use in pig production should be re-evaluated and its dosing and usage optimised. Moreover, the search for competitive alternatives to using colistin with swine is of paramount importance to preserve the effectiveness of this antibiotic for the treatment of MDR-GNB infections in human medicine.

Topics: Animal Husbandry; Animals; Anti-Bacterial Agents; Biological Evolution; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Gene Transfer, Horizontal; Humans; Selection, Genetic; Swine

In this Leading article, we summarize current knowledge of the occurrence of the first and so far only transferable colistin resistance gene, mcr-1 Its location on a conjugative plasmid is likely to have driven its spread into a range of enteric bacteria in humans and animals. Screening studies have identified mcr-1 in five of the seven continents and retrospective studies in China have identified this gene in Escherichia coli originally isolated in the 1980s, while the first European isolate dates back to 2005. Based on the widespread use of colistin in pigs and poultry in several countries and the higher number of mcr-1-carrying isolates of animal origin than of human origin, it is tempting to assume that this resistance may have emerged in the animal sector. Whatever its origin, interventions to reduce its further spread will require an integrated global one-health approach, comprising robust antibiotic stewardship to reduce unnecessary colistin use, improved infection prevention, and control and surveillance of colistin usage and resistance in both veterinary and human medicine.

Topics: Animal Husbandry; Animals; Anti-Bacterial Agents; China; Colistin; Drug Resistance, Bacterial; Drug Utilization; Enterobacteriaceae; Enterobacteriaceae Infections; Gene Transfer, Horizontal; Health Policy; Humans; Poultry; Swine

Carbapenem-resistant Enterobacteriaceae (CRE) is a worldwide challenge and associated with a high mortality rate in critically ill patients. This review focused on rapid diagnosis, optimization of antimicrobial therapy, and implication of effective infection control precautions to reduce impact of CRE on vulnerable patients.. Several new diagnostic assays have recently been described for the early diagnosis of CRE. Retrospective studies are supportive for colistin plus meropenem combination for the treatment of CRE infections; however, solid evidence is still lacking. Ceftazidime-avibactam may be an effective therapeutic agent for infections caused by carbapenem-hydrolyzing oxacillinase-48 and Klebsiella pneumoniae carbapenamase-producing Enterobacteriaceae, but not for New Delhi metallo-β-lactamase producers. Gastrointestinal screening may permit early identification of patients with CRE infections. There is not enough evidence to recommend selective digestive decontamination for CRE carriers.. The information for rapid diagnosis of CRE is accumulating. There are new agents with high in-vitro activity against CRE, but clinical experience is limited to case reports. Active surveillance with a high rate of compliance to basic infection control precautions seems to be the best approach to reduce the impact of CRE on vulnerable patients.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactam Resistance; beta-Lactamases; Carbapenems; Ceftazidime; Colistin; Critical Illness; Drug Combinations; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meropenem; Retrospective Studies; Thienamycins

Colistin has been used in veterinary medicine for decades, mainly for the prevention and treatment of Enterobacteriaceae infections. However, data regarding colistin resistance in bacteria from animals and food of animal origin are relatively scarce, partly because there are methodological difficulties hampering the analysis of susceptibility to colistin. Most data regarding clinical isolates are related to enteropathogenic Escherichia coli and Salmonella. The resistance percentages are sometimes high for pathogenic strains, and the mcr-1 gene has been detected in pathogenic E. coli isolates from pigs, cattle and poultry in different countries. The prevalence of colistin resistance in Salmonella from healthy animals is usually low but depends on the proportion of intrinsically colistin-resistant serotypes. For indicator E. coli, the resistance levels are often very low, although higher levels have been observed in Asia. The mcr-1 gene has been detected in indicator E. coli from pigs, cattle, poultry and their products. Thus, there is an urgent need to re-assess the use of colistin in livestock throughout the world to ensure a global strategy for preserving this last-resort antimicrobial.

Topics: Animals; Anti-Bacterial Agents; Cattle; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Global Health; Meat Products; Poultry; Prevalence; Swine

The objective of this study was to describe the microbiological characteristics of an extensively drug-resistant (XDR) isolate of Morganella morganii obtained from a patient with sepsis of urinary origin and to describe the patient's clinical characteristics. We further aimed to perform a literature review of the situation in Latin America regarding Gram-negative bacillus (GNB) carriers of New Delhi metallo-β-lactamase (NDM-1) and qnr genes and current reports on the treatment of infections caused by XDR enterobacteria, with particular attention to colistin-resistant isolates.. The patient's clinical data were obtained from his medical history. Microbiological identification and susceptibility testing were done using the VITEK 2 Compact System. Resistance genes were detected by PCR and sequencing.. Blood and urine cultures grew an M. morganii isolate (Mm4232) harboring NDM-1 and qnrD1. The patient was treated successfully with fosfomycin and double doses of meropenem. There are no previous reports of the use of fosfomycin and meropenem to treat infections by XDR enterobacteria harboring NDM-1 carbapenemase.. This is the first report of qnrD1 in South America. We consider that this report could be helpful to physicians implementing treatments for infections caused by XDR GNB, including colistin-carbapenem-resistant GNB.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae Infections; Fosfomycin; Humans; Male; Meropenem; Morganella morganii; Sepsis; South America; Thienamycins; Young Adult

To address the therapeutic management of carbapenem-resistant Enterobacteriaceae on the basis of literature of the last 12 months.. Retrospective and prospective (nonrandomized noncontrolled) studies provide data regarding the management of infections due to carbapenem-resistant Enterobacteriaceae. The combination of a carbapenem with colistin or high-dose tigecycline or aminoglycoside or even triple carbapenem-containing combinations if the minimum inhibitory concentration (MIC) range of carbapenem (meropenem and imipenem) resistance is 8 mg/l or less seems to have an advantage over monotherapy with either colistin or tigecycline or fosfomycin. For Enterobacteriaceae with MIC for carbapenems over 8 mg/l, combination regimens involve colistin, tigecycline usually administered in a double dose than that suggested by its manufacturer, fosfomycin and aminoglycosides in various combinations.. Suggestions based on the limited literature cannot be made safely. Combination regimens involving carbapenems for Enterobacteriaceae with MICs 8 mg/l or less for carbapenems (in dual combination with colistin or high-dose tigecycline or aminoglycoside or even triple combinations) seem to confer some therapeutic advantage over monotherapy. For Enterobacteriaceae with higher than the above-mentioned MICs, a combination of two or even three antibiotics among colistin, high-dose tigecycline, aminoglycoside and fosfomycin seems to confer decreased mortality.

Topics: beta-Lactam Resistance; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Infection Control; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Practice Patterns, Physicians'; Prospective Studies; Retrospective Studies; Tigecycline; Treatment Outcome

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) highlights the importance of effective antibiotics to maintain the safety of our health care system. Clinicians will encounter CRE as a cause of difficult-to-treat and often fatal infections in hospitalized patients. We review the mechanisms of carbapenem resistance, the dissemination and clinical impact of these resistant organisms, and challenges to their detection, treatment, and control.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Klebsiella pneumoniae; Minocycline; Tigecycline

Topics: Anti-Bacterial Agents; Cephalosporins; Chloramphenicol; Colistin; Drug Hypersensitivity; Enterobacteriaceae Infections; Erythromycin; Female; Gonorrhea; Humans; Kidney Diseases; Mycoplasma Infections; Pelvic Inflammatory Disease; Salpingitis; Staphylococcal Infections; Streptococcal Infections; Streptomycin; Tetracycline; Thrombophlebitis; Tuberculosis, Female Genital; Wound Infection

To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients.. Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed.. MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24-2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea.. DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.

Topics: Administration, Oral; Aged; Anti-Bacterial Agents; Carrier State; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Neomycin; Organ Transplantation; Rectum; Transplant Recipients

Intestinal carriage with extended spectrum β-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE.. Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4-6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT).. Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted.

Topics: Administration, Oral; Aged; Anti-Bacterial Agents; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carrier State; Colistin; Drug Administration Schedule; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Fecal Microbiota Transplantation; Feces; Female; Humans; Male; Middle Aged; Tertiary Care Centers

Topics: Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Colistin; Creatinine; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Healthcare-Associated Pneumonia; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Sample Size; Sisomicin

To describe the incidence and microbiological features of carbapenemase-producing Enterobacteriaceae (CPE) from colonized patients in a Spanish university hospital during a cluster-randomized study [the Resistance of Gram-Negative Organisms: Studying Intervention Strategies (R-GNOSIS) project] on isolation strategies for faecal ESBL carriers.. From March 2014 to March 2016, 15 556 rectal swabs from 8209 patients admitted in two surgical wards and two medical wards were collected and seeded on ESBL and CPE chromogenic agars. Carbapenemase characterization (PCR and sequencing) was performed, and antibiotic susceptibility (MIC), clonality (PFGE and MLST) and diversity (Simpson diversity index estimation) were determined.. One hundred and ninety-eight CPE isolates, mainly Klebsiella pneumoniae (53.5%) and Escherichia coli (19.2%), were identified in 162 patients (2%). Prevalence of CPE carriage remained unchanged over time. Overall, amikacin (9.6%), tigecycline (9.6%) and colistin (0.5%) showed low non-susceptibility. The most frequent carbapenemase was OXA-48 (64.1%), followed by VIM-1 (26.8%), NDM-1 (5.3%) and KPC-3 (3.5%), and these were co-produced with ESBLs in 43.9%. OXA-48 plus CTX-M-15 was the most frequent association. Two major K. pneumoniae clones were identified (OXA-48-CTX-M-15-ST11 and VIM-1-SHV-12-ST54) with considerable genetic diversity among the remaining isolates, including OXA-48-E. coli. Species diversity tended to decrease from 0.75 in the first 6 months of the study to 0.43 in the final months. The emergence of new clones (i.e. OXA-48-Kluyvera spp. and NDM-1-K. pneumoniae ST437 and ST101) and displacement of other particular clones were also demonstrated.. We describe a polyclonal and changeable CPE population over time. Coexistence of worldwide disseminated clones, such as ST11-OXA-48- K. pneumoniae, with unrelated and emerging OXA-48-E. coli clones, depicts a disturbing CPE epidemiology in our institution.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; Bacterial Typing Techniques; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Colistin; DNA, Bacterial; Enterobacteriaceae Infections; Female; Genetic Variation; Hospitals, University; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Spain; Time Factors

Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) are an increasingly frequent cause of infections in the community and the healthcare setting. In this study, we aimed to investigate whether intestinal carriage of ESBL-E can be eradicated.. We conducted a double-blind, randomized, placebo-controlled, single-centre trial to assess the efficacy of an oral decolonization regimen on intestinal ESBL-E carriage in adult patients with an ESBL-E-positive rectal swab. Fifty-eight patients were allocated 1 : 1 to either placebo or colistin sulphate (50 mg 4×/day) and neomycin sulphate (250 mg 4×/day) for 10 days plus nitrofurantoin (100 mg 3×/day) for 5 days in the presence of ESBL-E bacteriuria. The primary outcome was detection of ESBL-E by rectal swab 28 ± 7 days after the end of treatment. Missing primary outcome data were imputed based on the last available observation. Additional cultures (rectal, inguinal and urine) were taken on day 6 of treatment and on days 1 and 7 post-treatment. The study protocol has been registered with ClinicalTrials.gov (NCT00826670).. Among 54 patients (27 in each group) included in the primary analysis, there was no statistically significant difference between the groups with regard to the primary outcome [14/27 (52%) versus 10/27 (37%), P = 0.27]. During treatment and shortly afterwards, there was significantly lower rectal ESBL-E carriage in the treatment group: 9/26 versus 19/22 on day 6 of treatment (P < 0.001) and 8/25 versus 20/26 on day 1 post-treatment (P = 0.001). This effect had disappeared by day 7 post-treatment (18/27 versus 17/25, P = 0.92). Liquid stools were more common in the treatment group (7/27 versus 2/29, P = 0.05).. The regimen used in this study temporarily suppressed ESBL-E carriage, but had no long-term effect.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Carrier State; Colistin; Double-Blind Method; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; Female; Framycetin; Gastrointestinal Tract; Humans; Male; Middle Aged; Placebos; Treatment Outcome; Young Adult

To study the efficacy of intestinal decontamination by oral nonabsorbable antibiotic agents to control a nosocomial outbreak of intestinal colonization and infection with multiresistant Enterobacteriaceae, and to examine its effects on endemic nosocomial infection rates.. A 10-week prospective incidence study (group 1), and then an 8-week randomized, open trial of intestinal decontamination (groups 2 and 3).. A medical intensive care unit of a tertiary care university hospital.. Consecutive patients with unit stay of over 2 days and a severity score at admission of more than 2; 124 patients were included in group 1, 50 in group 2 (control), and 36 in group 3 (intestinal decontamination).. Neomycin, polymyxin E, and nalidixic acid were given to group 3 patients throughout their stay in the unit.. Intestinal colonization with multiresistant strains occurred in 19.6% of patients in group 1, at a mean of 16 days after admission, and preceded detection in clinical samples by a mean of 11 days. During the decontamination trial, intestinal colonization rates decreased to 10% (group 2), and 3% (group 3) (P = 0.12 and P less than 0.01, compared with group 1, respectively). Corresponding infection rates were 9% (group 1), 3% (group 2), and 0 (group 3). No new cases were detected in the following 4 months. The intestinal colonization rate with gram-positive cocci was higher in group 3 than group 2 (P less than 0.001). The overall rate of nosocomial infections was at 28% (group 1), 33% (group 2), and 32% (group 3).. Intestinal decontamination can help to control an outbreak of intestinal colonization and infection with multiresistant gram-negative bacilli in the intensive care unit, but should not be recommended for routine prevention of endemic nosocomial infections.

Topics: Adult; Aged; Anti-Bacterial Agents; Cephalosporins; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Intensive Care Units; Intestines; Klebsiella pneumoniae; Middle Aged; Nalidixic Acid; Neomycin; Paris; Random Allocation; Risk Factors

In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 intensive care patients were randomly allocated into a control group and a study group. The study group received oral nonabsorbable antimicrobial agents (i.e., tobramycin, amphotericin B, and polymyxin E) in addition to parenteral antibiotics. Colonization with Gram-negative microorganisms in the oropharynx, and respiratory and digestive tracts increased in the control group during their stay, while the study group did not tend to colonize with Gram-negative bacteria. In the control group, 107 nosocomial infections were diagnosed, vs. 42 nosocomial infections in the study group. Nosocomial infections caused by Gram-negative bacteria were significantly less frequent in the study group. Mortality due to an acquired infection was significantly less frequent in the study group. We conclude that colonization, infection, and subsequent mortality by nosocomial Gram-negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Bacteria; Cefotaxime; Child; Colistin; Cross Infection; Digestive System; Drug Therapy, Combination; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Oropharynx; Prospective Studies; Pseudomonas Infections; Random Allocation; Respiratory System; Tobramycin

113 patients being treated for acute non-lymphoblastic leukaemia were investigated to determine the effect of suppression of body microbial flora on prevention of infection. They were randomly allocated to a control group or a group which received non-absorbed antibiotics by mouth and topical applications of cutaneous and mucosal antiseptic preparations. The group receiving oral non-absorbed antibiotics had significantly few infections, fewer deaths from infection, fewer pyrexial episodes, and consequently received less systemic antibiotic therapy than the controls.

Topics: Acute Disease; Administration, Oral; Administration, Topical; Adolescent; Adult; Antineoplastic Agents; Bacterial Infections; Bacteroides Infections; Chlorhexidine; Colistin; Drug Combinations; Enterobacteriaceae Infections; Framycetin; Humans; Leukemia; Nystatin; Remission, Spontaneous; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections

Topics: Adult; Aerosols; Aged; Bronchitis; Chronic Disease; Colistin; Dyspnea; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Histamine H1 Antagonists; Humans; Kanamycin; Male; Middle Aged; Pseudomonas; Pseudomonas Infections; Respiratory Therapy; Sputum; Ventilators, Mechanical; Virulence

In the last years, Enterobacter cloacae complex has become an important threat associated with nosocomial infections (including bacteraemia). These bacteria have the ability to acquire mobile genetic elements with antimicrobial resistance genes, reducing the number of therapies available for treatment of the infections they cause. Multidrug resistant isolates of the E. cloacae complex have been causing blood stream infections in a hospital in northern Spain. The aim of this study was to report the spread of E. cloacae complex isolates carrying bla. All Enterobacter spp. isolates recovered from blood cultures of patients admitted to a tertiary Spanish hospital, over a five-year period were recovered. Of those, OXA-48-producing isolates were selected for further analysis (19 E. xiangfangensis isolates and a single E. hoffmannii). Bacterial identification, antimicrobial susceptibility, DNA sequencing, molecular typing, resistome analysis and plasmid characterization was performed.. The presence of bla

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Plasmids; Spain

Colistin (CST) is a last-line drug for multidrug-resistant Gram-negative bacterial infections. CST-heteroresistant Enterobacter cloacae complex (ECC) has been isolated. However, integrated analysis of epidemiology and resistance mechanisms based on the complete ECC species identification has not been performed.. Clinical isolates identified as "E. cloacae complex" by MALDI-TOF MS Biotyper Compass in a university hospital in Japan were analyzed. Minimum inhibitory concentrations of CST were determined by the broth microdilution method. The population analysis profiling (PAP) was performed for detecting the heteroresistant phenotype. The heat shock protein 60 (hsp60) cluster was determined from its partial nucleotide sequence. From the data of whole-genome sequencing, average nucleotide identity (ANI) for determining ECC species, multilocus sequence type, core genome single-nucleotide-polymorphism-based phylogenetic analysis were performed. phoPQ-, eptA-, and arnT-deleted mutants were established to evaluate the mechanism underlying colistin heteroresistance. The arnT mRNA expression levels were determined by reverse transcription quantitative PCR.. Thirty-eight CST-resistant isolates, all of which exhibited the heteroresistant phenotype by PAP, were found from 138 ECC clinical isolates (27.5%). The prevalence of CST-resistant isolates did not significantly differ among the origin of specimens (29.0%, 27.8%, and 20.2% for respiratory, urine, and blood specimens, respectively). hsp60 clusters, core genome phylogeny, and ANI revealed that the CST-heteroresistant isolates were found in all or most of Enterobacter roggenkampii (hsp60 cluster IV), Enterobacter kobei (cluster II), Enterobacter chuandaensis (clusters III and IX), and Enterobacter cloacae subspecies (clusters XI and XII). No heteroresistant isolates were found in Enterobacter hormaechei subspecies (clusters VIII, VI, and III) and Enterobacter ludwigii (cluster V). CST-induced mRNA upregulation of arnT, which encodes 4-amino-4-deoxy-L-arabinose transferase, was observed in the CST-heteroresistant isolates, and it is mediated by phoPQ pathway. Isolates possessing mcr-9 and mcr-10 (3.6% and 5.6% of total ECC isolates, respectively) exhibited similar CST susceptibility and PAP compared with mcr-negative isolates.. Significant prevalence (approximately 28%) of CST heteroresistance is observed in ECC clinical isolates, and they are accumulated in specific species and lineages. Heteroresistance is occurred by upregulation of arnT mRNA induced by CST. Acquisition of mcr genes contributes less to CST resistance in ECC.

Topics: Anti-Bacterial Agents; Colistin; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Nucleotides; Phylogeny; Prevalence

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; Humans; Lipid A; Microbial Sensitivity Tests; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry

Enterobacter kobei is an emerging cause of outbreak of nosocomial infections in neonatal intensive care units (NICUs). Between July and September 2016, a NICU in a tertiary care hospital of Nepal observed an abrupt increase in the number of neonatal sepsis cases caused by Enterobacter spp. infecting 11 out of 23 admitted neonates, five of whom died of an exacerbated sepsis.. To confirm the suspected outbreak, identify environmental source of infection, and characterize genetic determinants of antimicrobial resistance (AMR) and virulence of the pathogen.. Whole-genome sequencing of all Enterobacter spp. isolated from blood cultures of septic neonates admitted to NICU between May 2016 and December 2017 was performed. Also, an environmental sampling was intensified from fortnightly to weekly during the outbreak.. The genomic analysis revealed that 10 out of 11 non-duplicated E. kobei isolated from neonatal blood cultures between July and September 2016 were clonal, confirming the outbreak. The isolates carried AMR genes including bla. Our study underscored the need to implement stringent infection control measures to prevent infection outbreaks. For the first time, we report the emergence of carbapenem and colistin non-susceptible E. kobei carrying mcr-10 gene as a cause of nosocomial neonatal sepsis in a NICU.

Topics: Carbapenems; Colistin; Cross Infection; Disease Outbreaks; Enterobacter; Enterobacteriaceae Infections; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Microbial Sensitivity Tests; Neonatal Sepsis; Nepal; Tertiary Care Centers

Enterobacter is a major nosocomial genus of Enterobacteriaceae responsible for a variety of nosocomial infections, particularly in prolonged hospitalized patients in the intensive care units. Since current antibiotics have failed treating colistin- and carbapenem-resistant Enterobacteriaceae, efforts are underway to find suitable alternative strategies. Therefore, this study conducted a reverse vaccinology (RV) to identify novel and putative immunogenic targets using core proteome of 20 different sequence types (STs) of clinical Enterobacter spp. Moreover, we introduced a structural-based approach for exploration of potential vaccine candidates against the Enterobacteriaceae family using their conserved domain analysis.. A number of 2616 core coding sequences (CDSs) were retrieved from 20 clinical strains of Enterobacter spp. with a similarity of ≥ 50%. Nine proteins with a score of ≥ 20 considered as the shortlisted proteins based on the quartile scoring method, including three TonB-dependent receptors, WP_008500981.1, WP_058690971.1 and WP_058679571.1; one YjbH domain-containing protein, WP_110108068.1; three flagellar proteins, WP_088207510.1, WP_033145204.1 and WP_058679632.1; one spore-coat U domain-containing protein, WP_039266612.1; and one DD-metalloendopeptidase family protein, WP_025912449.1. In this study, proteins WP_058690971.1 and WP_110108068.1 were detected as the top candidates with regard to immune stimulation and interactions with TLRs. However, their efficacy is remaining to be evaluated experimentally.. Our investigation introduced common ferrichrome porins with high sequence similarity as potential vaccine candidates against the Enterobacteriaceae family. These proteins belong to the iron acquisition system and possess all criteria of suitable vaccine targets. Therefore, they need to be specifically paid attention for vaccine development against clinically important members of Enterobacteriaceae family.

Topics: Anti-Bacterial Agents; Colistin; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Ferrichrome; Genomics; Humans; Iron; Metalloendopeptidases; Porins; Proteome

Since 2016, several mobile colistin resistance (mcr) genes have been identified worldwide. It's worth noting that only mcr-1, mcr-3, mcr-8, and mcr-10 have been reported isolated directly from clinical samples which created greater risk to human health than other mcr gene types. A novel Quadruplex polymerase chain reaction (Quad-PCR) protocol was developed to detect and genotype transferable colistin-resistance genes (mcr-1, mcr-3, mcr-8, mcr-10) in Enterobacteria for clinical laboratory purposes. The protocol was validated by testing 11 clinical isolates of Escherichia coli and 3 clinical isolates of Klebsiella of human origin, each well characterized and prospectively validated. The Quad-PCR assay showed full concordance with whole-genome sequence data and displayed higher sensitivity and 100% specificity. The Quad-PCR assay achieved genotyping of mcr alleles (as singleton and mixture with double or triple gene types) described in one test.

Topics: Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; Fluorescence; Genotype; Humans; Molecular Diagnostic Techniques; Plasmids; Polymerase Chain Reaction; Reproducibility of Results; Sensitivity and Specificity; Time Factors

This Southeast Asia-Europe research project will use a One Health approach to identify the major parameters responsible for the presence of animal-associated antimicrobial resistant bacteria in animal production facilities in Thailand and the risk of their transmission from animals to humans. We will focus on traditional, small, extensive pig and poultry farms where information on antibiotic use is scarce and animals live in close contact with humans. This cross-sectional study will be based on the epidemiological analysis of the antimicrobial resistance (AMR) present in fecal samples from animals and humans. Extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) and Enterobacteriaceae resistant to colistin will be actively searched in the feces of farm animals (pigs and poultry), small wild rodents and farmers. Phenotypic (selective plating) and genotypic (multilocus seuquence typing and sequencing) methods will be used for the detection of AMR, the identification of antibiotic resistance genes (ARGs) and the characterization of strains carrying resistance genes. Questionnaires will be administered to investigate the effects of antibiotic use, farm characteristics and biosecurity measures on the occurrence of AMR in animals. Subsequently, the fecal carriage of AMR and ARGs in farmers will be compared to a control population with no occupational contacts with animals, thus enabling an estimation of the risk of transmission of AMR/ARGs from animals to farmers.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Chickens; Colistin; Cross-Sectional Studies; DNA, Bacterial; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Farmers; Feces; Humans; Multilocus Sequence Typing; Occupational Exposure; Surveys and Questionnaires; Swine; Thailand; Whole Genome Sequencing

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data.. The clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were "colonised" or "infected" with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes.. Altogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae. The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was bla. This study has revealed the genomic features of colonising CPE isolates, focusing on antimicrobial resistance and virulence determinants. This type of multi-layered analysis can be further exploited in Thailand and elsewhere to modify the regimes used for empirical antibiotic treatment and improve the management strategies for CPE infections in hospitalised patients.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Humans; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Molecular Epidemiology; Multilocus Sequence Typing; Phylogeny; Plasmids; Thailand; Virulence Factors; Whole Genome Sequencing

Plasmid-mediated colistin-resistance genes have been reported in human origin clinical samples worldwide which raises its threats to human infections. Notably, mcr-1, mcr-3, mcr-8, and mcr-10 have been reported isolated directly from clinical samples which creates more seriously threaten to human health than other mcr gene types. A multiplex polymerase chain reaction (Multi-PCR) protocol was developed to detect and genotype mobile colistin-resistance genes (mcr-1, mcr-3, mcr-8, mcr-10) in Enterobacteria for clinical laboratory purposes. We first designed four pairs of new primers for the amplification of mcr-1, mcr-3, mcr-8, and mcr-10 gene respectively to achieve stepwise separation of amplicons between 216 and 241 bp, and complete this Multi-PCR system with the assistance of another pair of universal primer. Among which the forward primers for mcr-8 and mcr-10 amplicons were identical. The protocol was validated by testing 11 clinical isolates of Escherichia coli and 3 clinical isolates of Klebsiella from human origin, each well characterized and prospectively validated. The Multi-PCR assay showed full concordance with whole-genome sequence data and displayed higher sensitivity and 100% specificity. The assay could detect all variants of the various mcr alleles described. The Multi-PCR assay successfully genotyped of mcr alleles described in one test.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Feces; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Plasmids

The emergence and spread of mobilized colistin resistance (mcr) genes are a global health concern.. In this study, we report the detection and genomic characterization of mcr-9 in a colistin-susceptible Enterobacter hormaechei (EH23) recovered from a pediatric patient in Lebanon.. EH23 was susceptible to colistin with a minimal inhibitory concentration (MIC) of 0.25 mg/L. Studying the mcr-9 genetic environment revealed that it was chromosomal and was bracketed by IS903 and IS26. QseCB, a two-component regulatory system, mediating the inducible expression of mcr-9 gene was not detected within the mcr-9 cassette but elsewhere on the genome. EH23 was 99.96% similar based on average nucleotide identity (ANI) to another mcr-negative E. hormaechei OIPH-N069 isolate recovered from Japan. wgSNP-based phylogenetic analysis divided all mcr-9 positive E. hormaechei isolates into five clades (I to V), with isolates from the same ST being clustered together.. The silent spread of mcr-9, particularly in the globally successful ST-78 Enterobacter lineage, is worrisome and requires close monitoring in humans and animals.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; Female; Genes, Bacterial; Genome, Bacterial; Humans; Infant; Lebanon; Microbial Sensitivity Tests

The aim of this study was to investigate the occurrence of the newly described transferable colistin resistance gene mcr-9 in extended-spectrum β-lactamase (ESBL)-producing clinical Enterobacteriaceae isolates from horses in Sweden.. A total of 56 whole-genome sequenced ESBL-producing Enterobacteriaceae isolates from horses were subjected to in silico detection of antimicrobial resistance genes and identification of plasmid replicons types. The colistin minimum inhibitory concentration (MIC) for mcr-positive isolates was determined by broth microdilution. Relatedness between Enterobacteriaceae carrying mcr genes was determined by multilocus sequence typing (MLST) and core genome MLST.. Thirty ESBL-producing Enterobacteriaceae isolates from horses were positive for the colistin resistance gene mcr-9. These isolates included Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Citrobacter freundii and belonged to diverse MLST sequence types within each species. Two of the mcr-9-containing isolates originated from the same horse. All mcr-9-positive isolates had colistin MICs below or equal to the EUCAST epidemiological cut-off value of 2 mg/L and were negative for the two potential regulatory genes qseB-like and qseC-like for mcr-9. Except for one isolate carrying only bla. The occurrence of mcr-9 was common among clinical ESBL-producing Enterobacteriaceae isolates from horses in Sweden and was linked to the ESBL-encoding gene bla

Topics: Animals; Bacterial Proteins; beta-Lactamases; Colistin; Computer Simulation; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; High-Throughput Nucleotide Sequencing; Horse Diseases; Horses; Microbial Sensitivity Tests; Multilocus Sequence Typing; Plasmids; Sweden; Whole Genome Sequencing

To undertake a prospective analysis of the occurrence of colistin-resistant and extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales colonizing pigs at two farms in Portugal, and to evaluate the putative correlations with usage of different antibiotics.. One hundred and two faecal samples recovered from two different Portuguese pig farms were screened for polymyxin-resistant and ESBL-positive Enterobacterales. The authors had undertaken a study at one of the farms previously, but the use of colistin has since been banned; zinc oxide and amoxicillin are used as prophylactic and curative drugs, respectively, at this farm. The other farm included in this study used zinc oxide alone.. Ninety-three ESBL-producing isolates (62 Escherichia coli, 29 Klebsiella pneumoniae, one Enterobacter aerogenes and one Enterobacter cloacae) and 17 colistin-resistant isolates (12 E. coli, four K. pneumoniae and one E. cloacae) were recovered. Among the ESBL producers, the majority (84%) produced CTX-M-15, while the others produced CTX-M-1 or CTX-M-9. Many different strain and plasmid backgrounds were identified, ruling out a massive dissemination of one major clone. In total, 17 colistin-resistant isolates were recovered, all from the first farm. All produced MCR-1, corresponding to 12 E. coli (10 clones) and three K. pneumoniae (two clones). The MCR-1 producers were all recovered from the farm where colistin had been used 2 years previously.. This study showed a surprisingly high rate of CTX-M-15 producers at two Portuguese pig farms. A link was found between antibiotic selective pressure (ß-lactam or polymyxin) and the corresponding resistance rate.

Topics: Animals; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter aerogenes; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Proteins; Klebsiella pneumoniae; Microbial Sensitivity Tests; Polymyxins; Portugal; Prospective Studies; Selection, Genetic; Swine

To characterize the colistin-resistant bacterial population in the gut and assess diversity of mcr-1 transmission within a single individual.. Large numbers of isolates (>100 colonies/chicken cecum sample) were collected from nine randomly selected mcr-1-positive chickens in China and used for comprehensive microbiological, molecular and comparative genomics analyses.. Of 1273 colonies, 968 were mcr-1 positive (962 Escherichia coli, two Escherichia fergusonii, two Klebsiella pneumoniae and two Klebsiella quasipneumoniae). One to six colistin-resistant species and three to 10 E. coli pulsed-field gel electrophoresis (PFGE) clusters could be identified from each sample. Whole-genome sequencing (WGS) analysis of the representative E. coli strains revealed three to nine sequence types observed in a single chicken host. The mcr-1 genes are located in either chromosomes or plasmids of different types, including IncI2 (n=30), IncHI2 (n=14), IncX4 (n=4), p0111(n=2) and IncHI1(n=1). Strikingly, in single cecum samples, one to five Inc type plasmids harbouring mcr-1 could be identified. Great diversity was also observed for the same IncI2 plasmid within a single chicken host. In addition, up to eight genetic contexts of the mcr-1 gene occurred within a single chicken.. There is extensive heterogeneity and flexibility of mcr-1 transmission in chicken gut due to bacterial species differences, distant clonal relatedness of isolates, many types and variations of mcr-positive plasmids, and the flexible genetic context of the mcr-1 gene. These compelling findings indicate that the gut is a 'melting pot' for active horizontal transfer of the mcr-1 gene.

Topics: Animals; Anti-Bacterial Agents; Cecum; Chickens; China; Colistin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Gene Transfer, Horizontal; Microbial Sensitivity Tests; Plasmids; Poultry Diseases; Whole Genome Sequencing

This study aimed to investigate the in vitro effects of a combination of antimicrobials other than colistin (CL) and tigecycline (TGC) on carbapenem-resistant Enterobacteriaceae (CRE).. We used 72 CRE strains including 65 carbapenemase-producing Enterobacteriaceae (CPE) that produce IMP-1, IMP-6, NDM, KPC, and OXA-48-like carbapenemases; and 7 carbapenemase-nonproducing Enterobacteriaceae (non-CPE) strains. These strains were assessed using antimicrobial susceptibility testing, breakpoint checkerboard (BC) plate method, and kill curve experiment to determine the effect of the combination therapy.. NDM, KPC, and OXA-48-like carbapenemase-producers showed higher MICs of carbapenem and aminoglycosides, and lower MICs of minocycline, compared to non-CPE and IMP-1/-6-producers. The results of the BC plate method suggested that the suitability of combinations of antimicrobials differ depending on the type of carbapenemases. Killing curve experiments demonstrated bactericidal or bacteriostatic action of the combination of antimicrobials even in sub-MIC concentrations of drugs. Our results suggest that the most effective antimicrobial combinations for each carbapenemase-producers are as follows; IMP-1 (tobramycin + tazobactam/piperacillin), IMP-6 (gentamicin + meropenem), NDM (minocycline + biapenem), KPC (arbekacin + doripenem) and OXA-48-like (minocycline + imipenem).. These results suggest that the combination of antimicrobials other than CL and TGC may be another candidate for the treatments of CPE infections, even though we have to choose effective antimicrobial combinations depending on the type of carbapenemase.

Topics: Anti-Infective Agents; Carbapenem-Resistant Enterobacteriaceae; Colistin; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Tigecycline

Topics: Carbapenem-Resistant Enterobacteriaceae; China; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Phylogeny

Multidrug-resistant organisms cause significant morbidity and mortality. Infections due to resistant gram-negative bacilli are increasingly being reported. For years, carbapenem antibiotics have been successfully used to treat infections due to resistant Enterobacteriaceae, such as

Topics: Aged, 80 and over; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Colistin; Enterobacteriaceae Infections; Female; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Peritonitis

Colistin is a last-resort antibiotic for the treatment of infections caused by multidrug and carbapenem-resistant Gram-negative bacteria. Colistin resistance has been emerging and multiple outbreaks have been reported in Europe and elsewhere. It has been most frequently reported in carbapenem-resistant K. pneumoniae. In this study, 24 multidrug and colistin-resistant clinical isolates (14 K. pneumoniae, one E. aerogenes, one E. cloacae, and eight A. baumannii) were collected from four hospitals in Croatia from 2013 to 2018, in order to analyse the molecular epidemiology and mechanisms of antibiotic resistance. β-lactamase and carbapenemase genes were detected by PCR. Genotyping was done on selected isolates by rep-PCR. Whole genome sequencing (WGS) was performed to discover possible molecular mechanisms for the observed colistin resistance. All isolates, except two K. pneumoniae isolates, were extensively drug resistant. Ten out of 16 (63%) K. pneumoniae isolates possessed bla

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Croatia; Cross Infection; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Phylogeny; Whole Genome Sequencing

There is limited data on the gut colonization rate of colistin resistant (Col-R) bacteria in patients and healthy volunteers in India. Aim of this study was to investigate the stool carriage rate of Col-R in hospitalized patients. Stool samples were inoculated in Eosin Methylene Blue agar plates supplemented with colistin. Colistin minimum inhibitory concentrations (MICs) were determined by the broth microdilution method. PCR for the mcr-1 was performed on Col-R Enterobacteriaceae isolates. Mutations in the mgrB gene were analyzed in K. pneumoniae isolates. Mcr-1 positive E. coli was subjected to whole-genome sequencing. Out of 65 stool samples screened, 33 (51%) samples carried Col-R bacteria. Majority (76.7%) of the isolates were sensitive to carbapenem.

Topics: Adult; Anti-Bacterial Agents; Carbapenems; Carrier State; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Proteins; Feces; Female; Hospitalization; Humans; India; Intestines; Klebsiella; Male; Microbial Sensitivity Tests; Mutation

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacter aerogenes; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests

The emergence and spread of mobilized colistin resistance (mcr) genes have triggered extensive concerns worldwide. Here, we characterized the global distribution of mcr-9, a newly-identified variant of mcr, by assembling the data set of mcr-9-positive isolates from GenBank database and the literature available. Genetic features of all the mcr-9-harboring plasmids were determined by bioinformatic analysis. We showed that mcr-9 is globally distributed in 21 countries across six continents, with a wide dissemination among various species of Enterobacteriaceae strains from human, animal, food and environment. IncHI2-ST1 plasmids were found to be the predominant replicon type carrying mcr-9. Comparative genomics highlighted that IncHI2-type plasmids may also serve as a critical reservoir of mcr-9, from which different types of circulating plasmids acquired the mcr-9. Results revealed that the rcnR-rcnA-pcoE-pcoS-IS903-mcr-9-wbuC structure was consistent in most mcr-9 cassettes, suggesting a relatively unitary model involved in the mobilization of mcr-9. It is most likely that the spread of mcr-9 was mainly attributed to the conjugation and recombination events of mcr-9-carrying plasmids. In summary, our results provide a comprehensive picture of the distribution and genetic environment of mcr-9, and demonstrate the central roles played by IncHI2 plasmids in the worldwide dissemination of mcr-9.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Colistin; DNA Restriction Enzymes; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Horses; Humans; Plasmids

Polymyxins have re-entered use against problem Gram-negative bacteria. Resistance rates are uncertain, with estimates confounded by selective testing.. The BSAC Resistance Surveillance Programme has routinely tested colistin since 2010; we reviewed data up to 2017 for relevant Enterobacterales (n = 10 914). Unexpectedly frequent resistance was seen among the Enterobacter cloacae complex isolates (n = 1749); for these, we investigated relationships to species, genome, carbon source utilization and LPS structure.. Annual colistin resistance rates among E. cloacae complex isolates were 4.4%-20%, with a rising trend among bloodstream organisms; in contrast, annual rates for Escherichia coli and Klebsiella spp. (including K. aerogenes) generally remained <2%. WGS split the E. cloacae complex isolates into seven genogroup clusters, designated A-G. Among isolates assigned to genogroups A-D, 47/50 sequenced were colistin resistant, and many of those belonging to genogroups A-C identified as E. asburiae. Isolates belonging to genogroups E-G consistently identified as E. cloacae and were rarely (only 3/45 representatives sequenced) colistin resistant. Genogroups F and G, the predominant colistin-susceptible clusters, were metabolically distinct from other clusters, notably regarding utilization or not of l-fucose, formic acid, d-serine, adonitol, myo-inositol, l-lyxose and polysorbates. LPS from resistant organisms grown without colistin pressure lacked substitutions with 4-amino-arabinose or ethanolamine but was more structurally complex, with more molecular species present.. Colistin resistance is frequent in the E. cloacae complex and increasing among bloodstream isolates. It is associated with: (i) particular genomic and metabolic clusters; (ii) identification as E. asburiae; and (iii) with more complex LPS architectures.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Genotype; Humans; Microbial Sensitivity Tests

Carbapenems are used in the treatment of infections caused by multidrug-resistant bacteria and colistin (polymyxin E) is used as the last choice of antimicrobial agent in those resistant to carbapenems. The worldwide and increased use of colistin, which causes cell death by disrupting the permeability of the cytoplasmic membrane of gram-negative bacteria, raised the problem of resistance. The transferable colistin resistance enzyme mcr, is a phosphoethanolamine transferase that adds phosphoethanolamine to lipid A and modifies lipopolysaccharides, leading to polymyxin resistance. The aim of this study was to investigate some of the most prevalent plasmid mediated colistin and carbapenemase resistance genes in colistin resistant Enterobacterales isolates. Enterobacterales isolates which were isolated in the samples of patients treated in the clinical units between October 2016 and September 2018 in the Karadeniz Technical University Faculty of Medicine Farabi Hospital Medical Microbiology Laboratory were included in the study. In addition to conventional methods, isolates were identified to the species level by MALDI-TOF MS (Bruker Daltonics, Germany). The antibiotic susceptibilities of Enterobacterales isolates were studied by an automated microbiology system (Phoenix, Becton Dickinson, USA) and evaluated according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. In isolates that are resistant to colistin, and the isolates that are found to be sensitive but should be included in the patient report of the colistin susceptibility test, colistin susceptibility tests were repeated with liquid microdilution method in accordance with EUCAST standards. The presence of extended spectrum beta-lactamase (ESBL), AmpC beta-lactamase and carbapenemase were determined by phenotypic methods according to EUCAST recommendations in colistin resistant Enterobacterales isolates. Furthermore, resistance genes of mcr-1-5, blaOXA-48, blaKPC, blaNDM, blaVIM, blaIMP were detected by polymerase chain reaction (PCR) method, followed by nucleotide sequence analysis of the amplified products. In our study, 14657 Enterobacterales isolates belonging to 7535 patients treated in different clinical units were examined retrospectively. Escherichia coli 61.2% (n= 8968), Klebsiella pneumoniae 22.7% (n= 3334) and Enterobacter cloacae 6.9% (n= 1005) were the most prevalent isolates. Carbapenem resistance was detected in 894 isolates, and 5.8% (n= 412) of 7135 iso

Topics: Aged; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Germany; Humans; Microbial Sensitivity Tests; Plasmids; Retrospective Studies

Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging global public health threat. As a reserve agent, colistin has been the drug of choice for the treatment of infections caused by CRE. The aim of this study was to determine the risk factors of carbapenem and colistin-resistant Enterobacteriaceae infections and to investigate the outcomes.. We conducted a retrospective study in a single university hospital between the years 2013 and 2017 including 150 patients with Enterobacteriaceae infections.. Of 150 Enterobacteriaceae infections, 62 (41%) were carbapenem and 23 (15%) were colistin-resistant. Colistin resistance rates among Enterobacteriaceae species increased from 4% in 2014 to 25% in 2017. The inhospital mortality of the patients with colistin-resistant and with carbapenem-resistant infections were 39% (9/23) and 45% (28/62), respectively. Prior exposure to polyantibiotic therapy for Gram negative bacteria was found as a predictor of CRE (OR = 6.4; 95% CI 3.07-13.6; p = 0.001) infections. The median length of hospital stay prior to positive culture (OR = 1.02; 95%CI, 1.0-1.04; p = 0.003) and history of surgery during the admission (OR = 2.46; 95% CI 1.2-5.1; p = 0.005) were found as the predictors of CRE infections. Underlying necrotizing enterocolitis and/or short-bowel syndrome (OR=6.38; 95%CI 1.16-35; p = 0.033) and mechanical ventilation prior to index culture were found as predictors of colistin resistance (OR = 9.4; 95% CI 2-40.4; p = 0.004).. Recognizing the risk factors of carbapenem and colistin resistant Enterobacteriaceae infections is essential in order to conserve carbapenem and colistin since there are no new antibiotics to treat multidrugresistant Enterobacteriaceae infections.

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Child; Colistin; Enterobacteriaceae Infections; Humans; Infant, Newborn; Retrospective Studies

Imipenem/relebactam, an investigational β-lactam/β-lactamase inhibitor combination for treatment of Gram-negative infections, and comparators including ceftazidime/avibactam, piperacillin/tazobactam and colistin were tested for activity against representative carbapenemase-producing Enterobacteriaceae (CPE) isolates.. MICs of the antimicrobial agents were determined using standard broth microdilution methodology for CPE isolates collected from Indiana patients, primarily during the time frame of 2013-17 (n = 199 of a total of 200 isolates). Inhibitors were tested at 4 mg/L in all combinations.. Of the CPE in the study, 199 produced plasmid-encoded KPC class A carbapenemases; 1 Serratia marcescens isolate produced the SME-1 chromosomal class A carbapenemase. MIC50/MIC90 values of imipenem/relebactam were ≤0.25/0.5 mg/L, whereas MIC50/MIC90 values of ceftazidime/avibactam were 1/2 mg/L. Resistance to colistin was observed in 54% (n = 97) of 180 non-Serratia isolates tested (MIC50 of 4 mg/L). Colistin resistance mechanisms included production of a plasmid-encoded mcr-1-like gene (n = 2) or an inactivated mgrB gene.. Imipenem/relebactam was the most potent agent tested against CPE in this study and may be a useful addition to the antimicrobial armamentarium to treat infections caused by these pathogens.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Imipenem; Indiana; Microbial Sensitivity Tests

The present study assessed the performance of Rapid Polymyxin™ NP test to detect colistin resistance directly from 132 blood cultures found positive for Enterobacterales by FilmArray. Additionally, colistin MICs of isolated microorganisms were determined by the commercial broth microdilution method ComASP™ Colistin, used as the gold standard comparator. The Rapid Polymyxin™ NP test correctly detected all colistin-resistant isolates. However, the test has misidentified as resistant 4 colistin-susceptible isolates (1 Escherichia coli and 3 Klebsiella pneumoniae). Molecular characterization of colistin-resistant isolates showed that K. pneumoniae, which belonged to ST15 and ST147, carried alterations in the mgrB. Moreover, the first Greek mcr-1-positive colistin-resistant E. coli was detected. The rapidity (2-3 h) of the results, combined with its excellent negative predictive value (100%), allows implementation of the test for routine testing of blood cultures mainly in the clinical settings that are endemic for carbapenem-resistant bacteria, avoiding misuse of colistin and preventing the spread of colistin-resistant bacteria.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Blood Culture; Colistin; Diagnostic Tests, Routine; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; False Positive Reactions; Greece; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests

A phenotypic assay based on colistin pre-diffusion and differential inhibition of Mobile Colistin Resistance (MCR) protein activity by EDTA showed that, of the 92 strains tested, all MCR producers (49) exhibited an increase ≥5 mm in the inhibition zone around the area of pre-diffusion in the presence of EDTA, in comparison with colistin alone. Results suggest that CPD-E may differentiate MCR-producing microorganisms from resistant microorganisms without this marker.

Topics: Animals; Anti-Bacterial Agents; Colistin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Bacterial; Edetic Acid; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids

Topics: Amikacin; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Enterobacteriaceae Infections; Humans; Meropenem; Microbial Sensitivity Tests; Multilocus Sequence Typing

Topics: Anti-Bacterial Agents; Colistin; Culture Media; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Proteins; False Negative Reactions; Humans; Microbial Sensitivity Tests; Sensitivity and Specificity

A carbapenem-resistant and colistin-heteroresistant clinical isolate of Enterobacter cloacae was obtained from an inpatient in Okinawa, Japan. The minimum inhibitory concentrations of both imipenem and meropenem were 32 μg/mL. The isolate showed heteroresistance to colistin using the Etest method and resistance to colistin using the broth microdilution method. It had a disrupted ompC and a mutation in the promoter region of bla

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Diarrhea; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Feces; Female; Humans; Japan; Microbial Sensitivity Tests; Mutation

The dissemination of carbapenemase-producing

Topics: Colistin; Culture Media; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Rectum

A multidrug resistant isolate, identified as Citrobacter amalonaticus using MALDI-TOF MS and confirmed by genomic analysis, was recovered from a pediatric patient in a hospital from Buenos Aires, Argentina. By whole-genome sequencing a total of 16 resistance genes were detected, including bla

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Citrobacter; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Phylogeny

When the problem with carbapenem-resistant Enterobacteriaceae (CRE) increases, the older antimicrobial agents such as colistin and fosfomycin are used for the treatment of these infections. In this study, the broth microdilution method for colistin and the agar dilution method for fosfomycin were used for a total of 147 multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains of CRE. The study included Klebsiella pneumoniae (91.16%), Escherichia coli (7.48%), Enterobacter cloacae (0.68%), and Serratia marcescens (0.68%). All these strains produce various types of carbapenemase, including OXA-48, NDM, and KPC. Some of these strains also have three different carbapenemase mechanisms, including OXA-48 (78.23%), NDM (2.04%), and KPC (0.68%) or OXA-48 and NDM (10.88%), or OXA-48 and KPC (0.68%). About 76.19% of the strains and 67.35% of the strains were resistant for colistin and fosfomycin, respectively. A total of 21 out of 35 colistin-susceptible strains were found to be susceptible to fosfomycin. This study showed that the resistance rates of colistin and fosfomycin are high. The MDR and XDR strains of CRE are spreading in our region and thus a monitoring system for CRE should be followed. Moreover, the applicability of antimicrobial stewardship programs should be increased in all inpatient and outpatient settings.

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Turkey

Polymyxin B and colistin are nephrotoxic drugs used in the treatment of carbapenem-resistant Enterobacteriaceae. The aim of this study is to evaluate the burden of costs due to polymyxin associated AKI and propose a simulated break-even price for new therapies.. The pharmacoeconomic model is based on two large cross-sectional studies of polymyxin nephrotoxicity. Total direct costs in patients with and without renal failure were compared. The direct cost of each hemodialysis section (USD82.94) and daily hospital charges (USD934.85) were based on the values used in a major public hospital in the city where the clinical study was performed. The break-even price of new drugs was simulated considering eventual new drugs as effective as polymyxins, but less nephrotoxic in different percentages. Outcomes of patients after hospital discharge were not evaluated.. Total direct cost of the group of patients who survived without AKI was significantly lower than total direct cost of the groups either with AKI or the group who died without AKI. There was a tendency of even higher costs in those who died with AKI and dialysis. Direct cost of hemodialysis was not as important as the longer hospitalization after sepsis. Considering daily cost of polymyxin is USD60, drugs with 50% less AKI could be considered cost-beneficial if the daily cost is lower than USD160.. AKI in patients with carbapenem-resistant Enterobacteriaceae treated with polymyxin increases both length of stay in hospital and total costs.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Brazil; Carbapenem-Resistant Enterobacteriaceae; Colistin; Cost of Illness; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Health Expenditures; Humans; Length of Stay; Male; Middle Aged; Models, Econometric; Polymyxin B; Renal Dialysis; Risk Factors

Colistin has become a last-resort antibiotic for the treatment of infections caused by highly drug-resistant Gram-negative bacteria. Moreover, it has been widely used in the livestock sector. As a consequence, colistin resistance is emerging worldwide. Among the colistin resistance mechanisms, the spread of the plasmid-encoded colistin resistance gene

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Capillary Action; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Humans; Immunoassay; Microbial Sensitivity Tests; Plasmids

The World Health Organization has categorized the Gram-negative superbugs, which are inherently impervious to many antibiotics, as critical priority pathogens due to the lack of effective treatments. The breach in our last-resort antibiotic (i.e., colistin) by extensively drug-resistant and pan-drug-resistant

Topics: Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Peptides

Topics: Colistin; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Mass Screening; Prospective Studies; Slovenia

To determine the influence of local spread of clonal strains and testing of follow-up isolates on categorical (CA) and essential agreement rates (EA) of common colistin (COL) drug susceptibility testing methods with the broth microdilution (BMD) reference method.. COL MICs were determined for 178 bacterial isolates (Enterobacteriaceae, n = 97; Pseudomonas aeruginosa, n = 81) collected within one year from 64 patients by BMD according to ISO standard 20776-1 (reference method), the SensiTest BMD panel (ST), agar dilution (AD), the VITEK 2 instrument, and gradient diffusion (GD) using antibiotic strips of two and Muller-Hinton agar plates of three manufacturers. CA and EA with BMD were calculated for all isolates and compared to the subset of 68 unique isolates.. CA ranges were 79.4% to 94.1% for the unique isolateq panel and 89.9% to 96.1% for all tested isolates. EA ranges were 64.7% to 86.8% and 67.4% to 91.0%, respectively. In both panels, EA for all GD assays was lower than 90%. Both lower and higher EA values ranging from-18.3% (MTS on BD agar) to + 6.3% (AD, Vitek 2) were observed in the full one-year sample. Acquisition of colistin resistance under therapy was observed for 3 patients.. i) Repeat testing and local spread of clonal strains can positively or negatively affect CA and EA, ii) CA is more robust towards local influences than EA, iii) EA of GD and AD methods for COL with the reference BMD method is insufficient.

Topics: Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections

Antibiotic-resistant bacteria are a significant threat to human health, with one estimate suggesting they will cause 10 million worldwide deaths per year by 2050, surpassing deaths due to cancer

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Ceftazidime; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacteriaceae Infections; Fosfomycin; Klebsiella; Microbial Sensitivity Tests

The escalation in carbapenem resistance among Enterobacteriaceae has resulted in a lack of effective therapeutic alternatives. Older antimicrobials, fosfomycin, nitrofurantoin and colistin for urinary tract infections (UTIs) caused by carbapenem-resistant Enterobacteriaceae (CRE) may be effective treatment options. The objectives of this study were to evaluate the utility of fosfomycin, nitrofurantoin and colistin in treating UTI caused by CRE and molecular characterization of the plasmid-mediated carbapenem resistance mechanisms.. Consecutive, non-duplicate isolates of CR Escherichia coli and Klebsiella spp. from urine cultures were included (n=150). Minimum inhibitory concentrations (MIC) were determined by E-test (fosfomycin and nitrofurantoin) and broth microdilution (colistin). Efficacy ratios were derived by dividing susceptibility breakpoints by observed MIC values of the drugs for the isolates. Isolates were screened for genes coding for carbapenemases using multiplex PCR. Fosfomycin, nitrofurantoin and colistin-resistant isolates were screened for plasmid-borne resistance genes fos A3, oqx AB and mcr-1, respectively using PCR.. Among E. coli, 98.9, 56 and 95 per cent isolates were susceptible to fosfomycin, nitrofurantoin and colistin, respectively, while 94 and 85 per cent of Klebsiella spp. were susceptible to fosfomycin and colistin, respectively. The efficacy ratios indicated fosfomycin as the drug of choice for UTI caused by CR E. coli and Klebsiella spp., followed by colistin. The bla. With increasing resistance against the current treatment options, older drugs may emerge as effective options. Molecular screening of resistant isolates is essential to prevent the spread of plasmid-borne resistance against these drugs.

Topics: Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Colistin; Enterobacteriaceae Infections; Fosfomycin; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Nitrofurantoin; Urinary Tract Infections

In an increasing number of cases the last therapeutic option for treatment of carbapenem-resistant Enterobacteriaceae is colistin. As the detection of colistin resistance is problematic and time-consuming, it is desirable to find a rapid and reliable test. The rapid polymyxin NP test developed by Nordmann et al. addresses this problem and has a sensitivity of 99.3  % and a specificity of 95.4  %, as described by the authors.. In this study, we aimed to evaluate the NP test and tested the effect of measuring the absorbance of the test with an enzyme-linked immunosorbent assay (ELISA) reader at 430 nm as an alternative objectified readout. We performed a study with 120 carbapenemase-producing Enterobacteriaceae isolates, including 40 colistin-resistant and 23 colistin-susceptible Klebsiella pneumoniae, 4 resistant and 23 susceptible Escherichia coli, and 20 susceptible and 10 resistant Enterobacter species, respectively.. Our data showed lower values for sensitivity and specificity than previously, namely only 91  % and 70 %, respectively, due to visual inspection. Furthermore, the results revealed a weakness in the correct detection of colistin-susceptible Enterobacter species. With the measurement of the absorbance we optimized the results to prevent misinterpretations of weak or inconclusive colour changes and enhanced the accuracy and objectivity of the rapid polymyxin NP test results.. We reinforced the rapid polymyxin NP test as a rapid and valuable tool for detecting colistin-resistant K. pneumoniae isolates, although false-positive results were obtained for several colistin-susceptible Enterobacter spp. By using the optimized method, we were able to increase the sensitivity and specificity values to 94  % and 95  %, respectively.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Enzyme-Linked Immunosorbent Assay; Humans; Microbial Sensitivity Tests; Polymyxins; Sensitivity and Specificity

For low-income countries, data regarding the intestinal colonization with extended-spectrum cephalosporin-resistant (ESC-R) and colistin-resistant (CST-R) Enterobacteriaceae in the community are still scarce. Here, we investigated this phenomenon by analysing hotel employees in Zanzibar.. During June to July 2018, rectal swabs from 59 volunteers were screened implementing selective enrichments and agar plates. Species identification was achieved using MALDI-TOF MS. Strains were characterized using microdilution panels (MICs), microarray, PCRs for mcr-1/-8, repetitive extragenic palindromic-PCR (rep-PCR) and WGS.. Colonization prevalence with ESC-R-, CST-R- and mcr-1-positive Enterobacteriaceae were 91.5%, 66.1% and 18.6%, respectively (average: 2.2 strains per volunteer). Overall, 55 ESC-R Escherichia coli (3 also CST-R), 33 ESC-R Klebsiella pneumoniae (1 also CST-R), 17 CST-R E. coli and 21 CST-R K. pneumoniae were collected. The following main resistance genes were found: ESC-R E. coli (blaCTX-M-15-like, 51.0%), ESC-R K. pneumoniae (blaCTX-M-9-like, 42.9%), CST-R E. coli (mcr-1, 55%) and CST-R K. pneumoniae (D150G substitution in PhoQ). ESBL-producing E. coli mainly belonged to ST361, ST636 and ST131, whereas all those that were mcr-1 positive belonged to ST46 that carried mcr-1 in a 33 kb IncX4 plasmid. ESBL-producing K. pneumoniae mainly belonged to ST17, ST1741 and ST101, whereas CST-R strains belonged to ST11.. We recorded remarkably high colonization prevalence with ESC-R and/or CST-R Enterobacteriaceae in hotel staff. Further research in the local environment, livestock and food chain is warranted to understand this phenomenon. Moreover, as Zanzibar is a frequent holiday destination, attention should be paid to the risk of international travellers becoming colonized and thereby importing life-threatening pathogens into their low-prevalence countries.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteriological Techniques; Carrier State; Cephalosporins; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Polymerase Chain Reaction; Prevalence; Rectum; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tanzania; Young Adult

The efficacy of ceftazidime-avibactam-a cephalosporin-β-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared with colistin remains unknown.. Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study. Efficacy, safety, and benefit-risk analyses were performed using intent-to-treat analyses with partial credit and the desirability of outcome ranking approaches. The ordinal efficacy outcome was based on disposition at day 30 after starting treatment (home vs not home but not observed to die in the hospital vs hospital death). All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW).. Thirty-eight patients were treated first with ceftazidime-avibactam and 99 with colistin. Most patients received additional anti-CRE agents as part of their treatment. Bloodstream (n = 63; 46%) and respiratory (n = 30; 22%) infections were most common. In patients treated with ceftazidime-avibactam versus colistin, IPTW-adjusted all-cause hospital mortality 30 days after starting treatment was 9% versus 32%, respectively (difference, 23%; 95% bootstrap confidence interval, 9%-35%; P = .001). In an analysis of disposition at 30 days, patients treated with ceftazidime-avibactam, compared with those treated within colistin, had an IPTW-adjusted probability of a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit analyses indicated uniform superiority of ceftazidime-avibactam to colistin.. Ceftazidime-avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase-producing CRE infections. These findings require confirmation in a randomized controlled trial.

Topics: Aged; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; Carbapenem-Resistant Enterobacteriaceae; Ceftazidime; Colistin; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Prospective Studies; Survival Analysis; Treatment Outcome

mcr-1-mediated colistin resistance in Enterobacteriaceae is concerning, as colistin is used in treating multidrug-resistant Enterobacteriaceae infections. We identified trends in human fecal mcr-1-positivity rates and colonization with mcr-1-positive, third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae in Guangzhou, China, and investigated the genetic contexts of mcr-1 in mcr-1-positive 3GC-R strains.. Fecal samples were collected from in-/out-patients submitting specimens to 3 hospitals (2011-2016). mcr-1 carriage trends were assessed using iterative sequential regression. A subset of mcr-1-positive isolates was sequenced (whole-genome sequencing [WGS], Illumina), and genetic contexts (flanking regions, plasmids) of mcr-1 were characterized.. Of 8022 fecal samples collected, 497 (6.2%) were mcr-1 positive, and 182 (2.3%) harbored mcr-1-positive 3GC-R Enterobacteriaceae. We observed marked increases in mcr-1 (0% [April 2011] to 31% [March 2016]) and more recent (since January 2014; 0% [April 2011] to 15% [March 2016]) increases in human colonization with mcr-1-positive 3GC-R Enterobacteriaceae (P < .001). mcr-1-positive 3GC-R isolates were commonly multidrug resistant. WGS of mcr-1-positive 3GC-R isolates (70 Escherichia coli, 3 Klebsiella pneumoniae) demonstrated bacterial strain diversity; mcr-1 in association with common plasmid backbones (IncI, IncHI2/HI2A, IncX4) and sometimes in multiple plasmids; frequent mcr-1 chromosomal integration; and high mobility of the mcr-1-associated insertion sequence ISApl1. Sequence data were consistent with plasmid spread among animal/human reservoirs.. The high prevalence of mcr-1 in multidrug-resistant E. coli colonizing humans is a clinical threat; diverse genetic mechanisms (strains/plasmids/insertion sequences) have contributed to the dissemination of mcr-1, and will facilitate its persistence.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carrier State; Cephalosporins; China; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Proteins; Feces; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Plasmids; Prevalence; Whole Genome Sequencing

A colistin-resistant Enterobacter aerogenes [study code 12264] was isolated from the tracheal aspirate of a 71-year-old male patient in the General Hospital [GH] in Pula, Croatia. The patient was previously treated in University Hospital Centre in Rijeka with colistin in order to eradicate Acinetobacter baumannii isolate, susceptible only to colistin and tigecycline. Genes encoding ESBLs [bla

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Croatia; Drug Resistance, Bacterial; Enterobacter aerogenes; Enterobacteriaceae Infections; Humans; Male; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Colistin; Cross Infection; DNA, Bacterial; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Genes, Bacterial; Humans; Limit of Detection; Molecular Typing; Multiplex Polymerase Chain Reaction; Real-Time Polymerase Chain Reaction

The Rapid Polymyxin NP test has been recently developed to rapidly detect polymyxin resistance in Enterobacteriaceae. Here we evaluated this test for detecting MCR-1/MCR-2-producing Enterobacteriaceae using a collection of 70 non-redundant strains either recovered from the environment, animals, or humans. Sensitivity and specificity were found to be 100%.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Enterobacter aerogenes; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Proteins; Humans; Klebsiella oxytoca; Klebsiella pneumoniae; Membrane Proteins; Microbial Sensitivity Tests; Polymyxins

Epidemiological studies have suggested an association between increased colistin use and selection for inherently colistin-resistant Enterobacteriaceae (ICRE). We aimed to evaluate whether colistin exposure is a risk factor for ICRE infection.. A matched 1:1 case-control study including patients recently hospitalized for ≥14 days with ICRE infection as cases matched with similar patients with a clinical isolate of a colistin-susceptible Enterobacteriaceae as controls was performed. Univariate analysis using McNemar test and multivariate analysis were conducted to explore risk factors for ICRE isolation, including colistin exposure 90 days before the positive culture.. We included 446 patients, 223 cases and 223 controls matched for gender, age, department, year, source of culture and duration of hospitalization before positive culture. Colistin exposure was significantly associated with ICRE isolation in both univariate (14/223, 6.3% of cases versus 4/223, 1.8% of controls, p 0.031) and multivariate analyses (odds ratio 4.415, 95% CI 1.078-18.082). Curtailed functional capacity was a significant risk factor for ICRE as well. Exposure to other broad-spectrum antibiotics was associated with isolation of a colistin-susceptible pathogen.. Exposure to colistin is associated with an increased risk of isolating an inherently colistin-resistant Enterobacteriaceae in patients with prolonged hospitalization. This should be taken into account while considering empirical therapy for such patients. Use of colistin should be judicious. The correlation between duration and magnitude of exposure and ICRE infection should be investigated in further studies.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Case-Control Studies; Colistin; Comorbidity; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Treatment Outcome

Plasmid-borne colistin resistance mediated by mcr-1 may contribute to the dissemination of pan-resistant Gram-negative bacteria. Here, we show that mcr-1 confers resistance to colistin-induced lysis and bacterial cell death, but provides minimal protection from the ability of colistin to disrupt the Gram-negative outer membrane. Indeed, for colistin-resistant strains of Enterobacteriaceae expressing plasmid-borne mcr-1, clinically relevant concentrations of colistin potentiate the action of antibiotics that, by themselves, are not active against Gram-negative bacteria. The result is that several antibiotics, in combination with colistin, display growth-inhibition at levels below their corresponding clinical breakpoints. Furthermore, colistin and clarithromycin combination therapy displays efficacy against mcr-1-positive Klebsiella pneumoniae in murine thigh and bacteremia infection models at clinically relevant doses. Altogether, these data suggest that the use of colistin in combination with antibiotics that are typically active against Gram-positive bacteria poses a viable therapeutic alternative for highly drug-resistant Gram-negative pathogens expressing mcr-1.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacter aerogenes; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Ethanolaminephosphotransferase; Klebsiella Infections; Klebsiella pneumoniae; Mice; Microbial Sensitivity Tests

Human fecal carriage of Enterobacteriaceae possessing mobilized colistin resistance genes (mcr-1 and mcr-2) remains obscure in Hong Kong. As part of routine surveillance on emerging antibiotic resistance, we conducted a prospective study on this topic in a regional hospital in Hong Kong.. From October 31 to November 25, 2016, all fecal specimens submitted for routine analysis were included in this surveillance study. These comprised 672 consecutive routine fecal specimens collected from 616 individuals. Fecal specimens were screened for colistin-resistant Enterobacteriaceae by culture-based method, and the presence of mcr-1 and mcr-2 genes in resistant isolates was identified by polymerase chain reaction and Sanger sequencing. Whole genome sequencing (WGS) of mcr-1-possessing Escherichia coli strains was facilitated using Illumina® MiSeq® followed by sequence analysis with appropriate bioinformatics tools.. Fourteen mcr-1-positive E. coli strains were isolated from 14 separate individuals (2.08% of total fecal specimens), with 9 of them being asymptomatic, healthy clients coming for health assessment. No mcr-2-possessing Enterobacteriaceae was identified. Colistin minimum inhibitory concentrations of these mcr-1-positive isolates ranged from 2 to 4 μg/mL. All these isolates were susceptible to carbapenems with 2 being extended spectrum β-lactamase producers. WGS data revealed that these isolates belonged to at least 12 different sequence types (STs) and possessed diversified plasmid replicons, virulence and acquired antibiotic resistance genes. Further study on an E. coli ST201 strain (Pasteur scheme) revealed coexistence of 47,818-bp IncP-1 and 33,309-bp IncX4 types of mcr-1 plasmids, which was a combination of stability and high transmissibility.. To the best of our knowledge, this is the first study on human fecal carriage of Enterobacteriaceae possessing mcr-1 and mcr-2 genes in Hong Kong. Our data further revealed asymptomatic carriage of mcr-1-possessing Enterobacteriaceae by both patients and healthy individuals. This is alarming considering wide diversity and high transmissibility of mcr-1 plasmids, which potentially facilitate emergence of pan-drug-resistant bacteria in future infection. This also highlights the importance of surveillance on emerging antibiotic resistance, especially for patients under intensive care.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; Child; Child, Preschool; Colistin; Cytochrome-B(5) Reductase; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Feces; Hong Kong; Hospitals; Humans; Infant; Microbial Sensitivity Tests; Middle Aged; Plasmids; Prospective Studies; Sequence Analysis, DNA; Whole Genome Sequencing

Background and aimPlasmid-mediated colistin resistance mechanisms have been identified worldwide in the past years. A multiplex polymerase chain reaction (PCR) protocol for detection of all currently known transferable colistin resistance genes (

Topics: Anti-Bacterial Agents; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Humans; Membrane Proteins; Microbial Sensitivity Tests; Multiplex Polymerase Chain Reaction; Plasmids; Salmonella; Transferases (Other Substituted Phosphate Groups)

To start a surveillance program to investigate the possible diffusion of mobilized colistin resistance genes in Enterobacteriaceae strains isolated in the Unit of Microbiology of the Great Romagna Hub Laboratory.. All the colistin resistant Enterobacteriaceae, isolated from August 1st 2016 to July 31st 2017, were prospectively evaluated for mcr-1 and mcr-2. Backdated survey of mcr-3, mcr-4 and mcr-5 was performed on the same group of isolates. Species identification was achieved by Vitek MS and the antibiotic susceptibility testing was performed both with Vitek-2 and Sensititre systems. Colistin resistant isolates were screened by PCR for the presence of the plasmid-mediated colistin resistance genes and amplicons were verified by sequencing. All mcr-1 positive isolates were subjected to MLST analysis.. Over the total of 19053 isolates belonging to Enterobacteriaceae, 90 were colistin resistant. The presence of mcr-1 was detected in 26 Escherichia coli. The overall prevalence of mcr-1 was 0.14%. The mcr-1 positive E. coli strains were assigned to 13 distinct sequence types (STs) according to MLST.. The prospective epidemiological survey carried out in our study gave a glimpse of the plasmid-mediated colistin resistance dissemination in Romagna. Since the prevalence rate of carbapenem resistant Enterobacteriaceae (CRE) in some hospital wards in our area is alarming, we underline the importance of a Surveillance Program to monitor the spread of the plasmid-mediated colistin resistance genes into MDR Gram-negative bacteria.

Topics: Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Eggs; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Food Contamination; Food Microbiology; Foodborne Diseases; Humans; Italy; Meat; Plasmids; Risk Factors

The increasing use of colistin has contributed to the emergence of resistant bacteria and to an increase in the frequency of infections caused by naturally resistant Enterobacteriaceae strains such as Proteus, Providencia, Morganella, and Serratia. In August 2016, the French High Council for Public Health (French acronym HCSP) received a request from the Ministry of Health on the advice of the French National Public Health agency (Santé publique France) with regard to measures that should be taken to tackle the emergence of plasmid-mediated colistin resistance among Enterobacteriaceae strains. French healthcare facilities were asked to take the necessary measures as soon as possible, such as updating the definition of emerging highly resistant bacteria and defining the identification methods so as to take account of the evolving epidemiology of this type of resistance. This article describes the epidemiological context of the discovery of this emergence in France and worldwide, the resistance mechanisms, the microbiological methods of routine laboratory detection and the level of hygiene measures to implement in French facilities.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Clinical Laboratory Techniques; Colistin; Communicable Disease Control; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids

The plasmid-located colistin resistance gene

Topics: Anti-Bacterial Agents; Bacteriological Techniques; Calcium; Colistin; Culture Media; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Klebsiella pneumoniae; Microbial Sensitivity Tests; Polymyxins

Few studies have addressed the molecular epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) isolates in the Arabian Peninsula, and such investigations have been missing from Dubai, a major economical, tourism and medical centre of the region. The antibiotic susceptibility, the carbapenemase type produced, and the clonality of 89 CRE strains isolated in five major Dubai hospitals in June 2015 to June 2016 were determined. Thirty-three percent of the collection of 70 Klebsiella pneumoniae, 13 Escherichia coli and 6 other Enterobacteriaceae were extremely drug resistant, 27% were resistant to colistin, and 4.5% (4 K. pneumoniae isolates) were resistant to all antibiotics tested. The colistin resistance rate in K. pneumoniae was 31.4%. None of the isolates carried mobile colistin resistance genes. Seventy-seven isolates produced carbapenemase: 53.3% OXA-48-like, 24.7% NDM and 22.1% both OXA-48-like and NDM, respectively. Pulsed-field gel electrophoresis clustered 50% of K. pneumoniae into a 35-membered group, which showed significant association with double carbapenemase production, with extreme drug resistance, and with being isolated from Emirati patients. Members of the cluster belonged to sequence type ST14. The rate of colistin resistance in K. pneumoniae ST14 was 37.1% vs. 27.1% of K. pneumoniae isolates outside of the cluster. Two of the panresistant K. pneumoniae isolates also belonged to ST14, whereas the other two were ST15 and ST231, respectively. In conclusion, beyond the overall high colistin resistance rate in CRE, the emergence of a highly resistant clone of K. pneumoniae ST14 in all Dubai hospitals investigated is a serious problem requiring immediate attention.

Topics: Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; United Arab Emirates

Antimicrobial resistance against colistin has emerged worldwide threatening the efficacy of one of the last-resort antimicrobials used for the treatment of Enterobacteriaceae. To investigate the presence of the recently identified colistin resistance genes (mcr-4, mcr-5) in China, we established PCRs to detect mcr-4 and mcr-5 on 213 anal and 1,339 nasal swabs from apparently healthy pigs (n = 1,454) in nine provinces, and 1,696 cloacal and 1,647 oropharyngeal samples from poultry (n = 1,836) at live-bird markets in 24 provinces of China. The prevalence of the mcr-4 in swine swabs (41.4%; 642/1,552) was significantly higher than in swabs from poultry (11.5%; 384/3,343). The mcr-4 gene was found in geese (49.5%, 54/109), chickens (17.2%, 257/1,498), pigeons (17.2%, 17/99) and ducks (15.4%, 20/130). In a similar trend, the prevalence of the mcr-5 in swine swabs (33.1%; 514/1552) was significantly higher than in swabs from poultry (5.6%; 187/3,343). The mcr-5 was identified in geese (17.4%, 19/109), chickens (9.9%, 148/1,498), ducks (7.7%, 10/130) and pigeons (3%, 3/99). The mcr-4 prevalence in the nasal swabs from pigs (59.2%, 58/98) was significantly higher than that in anal swabs (29.6%, 29/98) (P<0.001). Similarly, the mcr-5 prevalence in the nasal swabs from pigs (61.2%, 60/98) was significantly higher than in anal swabs (44.9%, 44/98) (P = 0.02), and significantly higher in oropharyngeal swabs (7.2%, 109/1,507) than in the cloacal swabs (3.7%, 56/1,507) (P<0.001). This study further confirms the presence of the mcr-4 and mcr-5 in animals and indicates these genes are prevalent and widespread in food producing animals (pig and poultry) in China. Future studies are needed to characterize the bacteria carrying the mcr-4 and mcr-5 and their locations on plasmids and/or the bacterial chromosomes, and determine co-resistances in the mcr-4 and mcr-5 positive strains.

Topics: Animals; Bacterial Proteins; China; Colistin; Digestive System; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Plasmids; Poultry; Prevalence; Swine

Colistin represents one of the few available drugs for treating infections caused by carbapenem-resistant Enterobacteriaceae. As such, the recent plasmid-mediated spread of the colistin resistance gene mcr-1 poses a significant public health threat, requiring global monitoring and surveillance. Here, we characterize the global distribution of mcr-1 using a data set of 457 mcr-1-positive sequenced isolates. We find mcr-1 in various plasmid types but identify an immediate background common to all mcr-1 sequences. Our analyses establish that all mcr-1 elements in circulation descend from the same initial mobilization of mcr-1 by an ISApl1 transposon in the mid 2000s (2002-2008; 95% highest posterior density), followed by a marked demographic expansion, which led to its current global distribution. Our results provide the first systematic phylogenetic analysis of the origin and spread of mcr-1, and emphasize the importance of understanding the movement of antibiotic resistance genes across multiple levels of genomic organization.

Topics: Americas; Anti-Bacterial Agents; Asia; Carbapenems; Colistin; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Europe; Evolution, Molecular; Gene Expression; Gene Transfer, Horizontal; Genome, Bacterial; Humans; Plasmids; Population Dynamics

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Humans; Microbial Sensitivity Tests; Plasmids; Salvage Therapy; Zidovudine

A set of 908 clinically derived colistin-resistant Enterobacteriaeae isolates collected worldwide in 2014-2016 were screened for the presence of the plasmid-borne mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5 genes. In total 3.2% (29/908) of the collection were positive for mcr, including 27 Escherichia coli, 1 Klebsiella pneumoniae and 1 Enterobacter cloacae. Twenty-four isolates possessed genes from the mcr-1 family, including the original mcr-1 (n = 22), as well as mcr-1.2 (n = 1) and mcr-1.5 (n = 1), which each differ from mcr-1 by encoding single amino acid variations. Genes from the mcr-3 family were found in isolates from Thailand, including mcr-3.1 (n = 3) and mcr-3.2 (n = 1). An E. coli isolated from a patient with a urinary tract infection in Colombia contained the recently discovered mcr-5. The full colistin-resistant collection was tested against a panel of antimicrobial agents with ceftazidime-avibactam and tigecycline exhibiting the highest activity.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Proteins; Ceftazidime; Colistin; Drug Combinations; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Epidemiological Monitoring; Humans; Internationality; Minocycline; Prevalence; Tigecycline

The isolation of a carbapenem-resistant Enterobacter cloacae strain harboring the IMI-1 variant of bla

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cephalosporins; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Japan; Levofloxacin; Microbial Sensitivity Tests

Efflux in bacteria is a ubiquitous mechanism associated with resistance to antimicrobials agents. Efflux pump inhibitors (EPIs) have been developed to inhibit efflux mechanisms and could be a good alternative to reverse colistin resistance, but only CCCP has shown good activity. The aim of our study was to identify CCCP activity in a collection of 93 Gram-negative bacteria with known and unknown colistin resistance mechanisms including isolates with mcr-1 plasmid-mediated colistin resistance.. Colistin MIC was evaluated with and without CCCP and the fold decrease of colistin MIC was calculated for each strain. In order to evaluate the effect of this combination, a time-kill study was performed on five strains carrying different colistin resistance mechanisms.. Overall, CCCP was able to reverse colistin resistance for all strains tested. The effect of CCCP was significantly greater on intrinsically colistin-resistant bacteria (i.e. Proteus spp., Serratia marcescens, Morganella morganii and Providencia spp.) than on other Enterobacteriaceae (P < 0.0001). The same was true for bacteria with a heteroresistance mechanism compared to bacteria with other colistin resistance mechanisms (P < 0.0001). A time-kill study showed the combination was bacteriostatic on strains tested.. These results suggest an efflux mechanism, especially on intrinsically resistant bacteria and Enterobacter spp., but further analysis is needed to identify the molecular support of this mechanism. EPIs could be an alternative for restoring colistin activity in Gram-negative bacteria. Further work is necessary to identify new EPIs that could be used in humans.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Proteins; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Plasmids; Proton Ionophores

A total of 18,656 Enterobacteriaceae and 4,175 Pseudomonas aeruginosa were consecutively collected from 85 US hospitals and tested for susceptibility by broth microdilution methods in a central monitoring laboratory (JMI Laboratories). The antimicrobial susceptibility and frequency of key resistance phenotypes were assessed and stratified by infection type as follows: bloodstream (BSI; 3,434 isolates; 15.0%), pneumonia (6,439; 28.2%), skin and skin structure (SSSI; 4,134; 18.1%), intra-abdominal (IAI; 951; 4.2%), and urinary tract (UTI; 7,873; 34.5%). Ceftazidime-avibactam was active against 99.9% to 100.0% of Enterobacteriaceae and 97.0% (pneumonia) to 99.4% (UTI) of P. aeruginosa isolates. Susceptibility rates were consistently lower for β-lactams, such as ceftazidime (82.3% vs. 87.1-90.8%), piperacillin-tazobactam (87.5% vs. 90.2-95.6%), and meropenem (96.8% vs. 98.4-99.4%) among Enterobacteriaceae from pneumonia compared to other infection types. Susceptibility to gentamicin was also generally lower among isolates from pneumonia, whereas susceptibility to levofloxacin and colistin were lowest among BSI and SSSI isolates, respectively. The occurrence of multidrug-resistance (MDR; 8.2% overall), extensively drug-resistance (XDR; 1.1% overall), and carbapenem-resistant Enterobacteriaceae (CRE; 1.3% overall) phenotypes were markedly higher among isolates from patients with pneumonia compared to other infection types. Among P. aeruginosa, susceptibility rates for ceftazidime, piperacillin-tazobactam, and gentamicin were lowest among isolates from pneumonia, whereas susceptibility to meropenem was similar among isolates from BSI, pneumonia, and IAI (77.3-77.9%), and susceptibility to levofloxacin was markedly lower among UTI isolates (67.1%). The frequencies of P. aeruginosa isolates with MDR and XDR phenotypes were highest among isolates from patients with pneumonia.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Colistin; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins; United States

A high prevalence of colistin resistance among. Colistin-resistant. This study demonstrates a stable low-level endemicity of MREb in two Dutch ICUs with prolonged use of SDD, which was characterized by the persistent presence of two clusters, suggesting incidental clonal transmission.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Gastrointestinal Diseases; Gastrointestinal Tract; Humans; Intensive Care Units; Microbial Sensitivity Tests; Polymorphism, Single Nucleotide; Prospective Studies; Retrospective Studies; Tobramycin; Whole Genome Sequencing

The spread of carbapenemase-producing Enterobacteriaceae in the Southwest Indian Ocean islands is poorly known. Here we describe an outbreak of colistin-resistant Enterobacter cloacae harbouring bla

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Cephalosporins; Colistin; Comoros; Disease Outbreaks; Electrophoresis, Gel, Pulsed-Field; Enterobacter cloacae; Enterobacteriaceae Infections; Ertapenem; Female; Genome, Bacterial; Humans; Imipenem; Male; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Young Adult

We investigated the colistin resistance rate among 356 Enterobacter spp. clinical isolates from eight hospitals in Korea. Antibiotic susceptibility testing was performed by broth microdilution. While 51 of 213 (23.9%) Enterobacter cloacae isolates were colistin-resistant, only six of 143 (4.2%) E. aerogenes isolates showed resistance. We also identified the skip well phenotype in eight E. cloacae and three E. aerogenes isolates. Multilocus sequence typing for E. cloacae and randomly amplified polymorphic DNA analysis and enterobacterial repetitive intergenic consensus PCR for E. aerogenes revealed that clonal spreading of colistin-resistant and skip well Enterobacter spp. isolates had not occurred. In vitro time-kill assays were performed with three colistin-resistant, three skip well, and two colistin-susceptible isolates of E. cloacae and E. aerogenes. Inconsistent results were observed among isolates with skip well phenotypes; while some were eradicated by 2 mg/L colistin, others were not. This suggests that skip well isolates have differentiated into different categories. As the high rates of colistin resistance in E. cloacae detected are of clinical concern, continuous monitoring is warranted. In addition, the clinical implications and mechanisms of the skip well phenotype should be investigated to ensure the appropriate use of colistin against Enterobacter infections.

Topics: Anti-Bacterial Agents; Colistin; DNA, Bacterial; Drug Resistance, Bacterial; Enterobacter; Enterobacter aerogenes; Enterobacter cloacae; Enterobacteriaceae Infections; Genotype; Humans; Microbial Sensitivity Tests; Phenotype; Republic of Korea; RNA, Ribosomal, 16S

Development and evaluations of the Rapid Polymyxin NP test for detection of colistin resistance in Enterobacteriaceae have been recently reported. In this study, we evaluated the performance of the test using a larger number of Enterobacteriaceae, and a larger proportion of isolates with a colistin MIC close to the breakpoint. Out of 339 isolates, the Rapid Polymyxin NP test detected colistin resistance in 13 isolates of Escherichia coli, 213 isolates of Klebsiella pneumoniae, 9 isolates of Enterobacter aerogenes, and 10 isolates of the other Enterobacteriaceae species. Sensitivity and specificity of the test for detecting colistin resistance were 100% and 95.9%, respectively. Positive predictive value and negative predictive value were 98.3% and 100%, respectively.

Topics: Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Polymyxins; Thailand

The commercial Rapid Polymyxin NP test was evaluated to detect colistin-resistant Enterobacteriaceae. A total of 223 enterobacterial isolates corresponding to 136 resistant (including 38 MCR-like producers), 19 heteroresistant, and 78 colistin-susceptible isolates were tested. The test was performed according to the manufacturer's instruction, and the color of the wells was read after 2 and 3 hours of incubation. The results were compared with those of the homemade Rapid Polymyxin NP test, and manual broth microdilution according to EUCAST guidelines was used as the reference method to determine the performance of the test. Excellent performance of the commercial Rapid Polymyxin NP test was found with a very major error rate, a major error rate, a sensitivity, and a specificity of 1.9%, 5.1%, 98.1%, and 94.9%, respectively. The performance of the homemade Polymyxin NP test was similar, with a slightly better value for the very major error (1.2 %).

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests; Polymyxins; Reagent Kits, Diagnostic; Sensitivity and Specificity; Time Factors

The emerging mobile colistin resistance gene, mcr-1, is an ongoing worldwide concern and an evaluation of clinical isolates harboring this gene is required in Korea. We investigated mcr-1-possessing Enterobacteriaceae among Enterobacteriaceae strains isolated in Korea, and compared the genetic details of the plasmids with those in Escherichia coli isolates from livestock.. Among 9,396 Enterobacteriaceae clinical isolates collected between 2010 and 2015, 1,347 (14.3%) strains were resistant to colistin and those were screened for mcr-1 by PCR. Colistin minimum inhibitory concentrations (MICs) were determined by microdilution, and conjugal transfer of the mcr-1-harboring plasmids was assessed by direct mating. Whole genomes of three mcr-1-positive Enterobacteriaceae clinical isolates and 11 livestock-origin mcr-1-positive E. coli isolates were sequenced.. Two E. coli and one Enterobacter aerogenes clinical isolates carried carried IncI2 plasmids harboring mcr-1, which conferred colistin resistance (E. coli MIC, 4 mg/L; E. aerogenes MIC, 32 mg/L). The strains possessed the complete conjugal machinery except for E. aerogenes harboring a truncated prepilin peptidase. The E. coli plasmid transferred more efficiently to E. coli than to Klebsiella pneumoniae or Enterobacter cloacae recipients. Among the three bacterial hosts, the colistin MIC was the highest for E. coli owing to the higher mcr-1-plasmid copy number and mcr-1 expression levels. Ten mcr-1-positive chicken-origin E. coli strains also possessed mcr-1-harboring IncI2 plasmids closely related to that in the clinical E. aerogenes isolate, and the remaining one porcine-origin E. coli possessed an mcr-1-harboring IncX4 plasmid.. mcr-1-harboring IncI2 plasmids were identified in clinical Enterobacteriaceae isolates. These plasmids were closely associated with those in chicken-origin E. coli strains in Korea, supporting the concept of mcr-1 dissemination between humans and livestock.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Chickens; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Proteins; Humans; Microbial Sensitivity Tests; Plasmids; Republic of Korea; Retrospective Studies; Whole Genome Sequencing

BackgroundEmergence of colistin resistance has been related to increased use in clinical settings, following global spread of carbapenem-resistant Gram-negative bacteria. Use of colistin in animal production may constitute a further source of spread of resistant strains to humans. We sought to determine risk factors for human colonisation or infection with colistin-resistant

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Case-Control Studies; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Escherichia coli; Hospitals, University; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Switzerland

Plasmid-mediated colistin resistance driven by the mcr-1 gene is of great clinical concern. Its diffusion in the hospital environment is unknown. We detected mcr-1-driven resistance in 8.3% of Enterobacteriaceae isolates from hospital surfaces in Italy, which might represent a reservoir of threatening nosocomial pathogens.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Colistin; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Hospitals; Humans; Italy; Microbial Sensitivity Tests

The environment, including farms, might act as a reservoir for mobile colistin resistance (mcr) genes, which has led to calls for reduction of usage in livestock of colistin, an antibiotic of last resort for humans.. To establish the molecular epidemiology of mcr Enterobacteriaceae from faeces of two cohorts of pigs, where one group had initially been treated with colistin and the other not, over a 5 month period following stoppage of colistin usage on a farm in Great Britain; faecal samples were also taken at ∼20 months.. mcr-1 Enterobacteriaceae were isolated from positive faeces and was WGS performed; conjugation was performed on selected Escherichia coli and colistin MICs were determined.. E. coli of diverse ST harbouring mcr-1 and multiple resistance genes were isolated over 5 months from both cohorts. Two STs, from treated cohorts, contained both mcr-1 and mcr-3 plasmids, with some isolates also harbouring multiple copies of mcr-1 on different plasmids. The mcr-1 plasmids grouped into four Inc types (X4, pO111, I2 and HI2), with mcr-3 found in IncP. Multiple copies of mcr plasmids did not have a noticeable effect on colistin MIC, but they could be transferred simultaneously to a Salmonella host in vitro. Neither mcr-1 nor mcr-3 was detected in samples collected ∼20 months after colistin cessation.. We report for the first known time on the presence in Great Britain of mcr-3 from MDR Enterobacteriaceae, which might concurrently harbour multiple copies of mcr-1 on different plasmids. However, control measures, including stoppage of colistin, can successfully mitigate long-term on-farm persistence.

Topics: Animals; Anti-Bacterial Agents; Colistin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Farms; Feces; Livestock; Microbial Sensitivity Tests; Plasmids; Swine; Time Factors; Transferases (Other Substituted Phosphate Groups); United Kingdom; Whole Genome Sequencing

mcr-1-mediated colistin resistance in bacteria is concerning, as colistin is used in treating multidrug-resistant bacterial infections. And mcr-1-producing bacteria have been identified in multiple sources. Up to 248 million people use public transportation daily in China, however; public transportation hasn't been studied as a potential source of community-based transmission of mcr-1. Herein we investigated mcr-1-producing isolates from public transportation and explored the genomic characteristics of them.. Surface samples were collected from public transportation in Guangzhou, China, from October 2016 to April 2017. Polymerase chain reaction was performed to detect mcr-1 gene, plasmid replicon type and phylogenetic group. Minimum inhibitory concentrations (MICs) were determined by microdilution method. S1-nuclease digestion and pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting were performed with mcr-1-harboring plasmids. Whole-genome sequencing was performed with mcr-1-producing isolates.. Of the 737 samples with bacterial growth, 26 isolates were positive for mcr-1, including 23 Escherichia coli and 3 Klebsiella pneumoniae isolates. The E. coli isolates belonged to phylogroups A and B1. Most mcr-1-producing isolates were resistant to ampicillin (25), cefotaxime (21), fosfomycin (16), and gentamicin (15). S1-PFGE, Southern blotting and replicon typing showed that mcr-1 was mainly located on ~33.3 kb to ~220 kb IncX4, IncI2 and IncHI2 plasmids in E. coli, while located on ~33.3 kb untyped plasmid in K. pneumoniae. Several sequence types (ST), including ST2253, ST101, ST10 complex and ST37, were revealed. Between 53 and 66 (mean = 61.8) resistance genes were identified among mcr-1-producing isolates.. Public transportation may serve as a source of mcr-1-producing bacteria.

Topics: Anti-Bacterial Agents; China; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Proteins; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Motor Vehicles; Plasmids; Polymerase Chain Reaction; Public Health; Railroads; Transportation; Whole Genome Sequencing

To investigate the in vitro and in vivo activity of imipenem-colistin combination against multidrug-resistant Enterobacter cloacae infections in order to determine whether it should be explored further.. The antimicrobial activity of colistin alone and in combination with imipenem was assessed versus an imipenem-susceptible isolate, E. cloacae GN1059, or an imipenem-resistant strain, E. cloacae GN0791, isolated in Anhui, China. The potential synergy of imipenem-colistin was evaluated using a checkerboard assay, as well as static time-kill experiments at 1× and 2× minimum inhibitory concentration (MIC). A simple invertebrate model (Galleria mellonella) was developed to assess the in vivo efficacy of imipenem-colistin in treating E. cloacae infection.. In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of ≤ 0.5) was observed between imipenem and colistin for both isolates tested. In time-kill assays, the combination of imipenem-colistin at 1× or 2× MIC resulted in complete killing of both strains. In the G. mellonella larvae model infected with lethal doses of E. cloacae, the combination therapy led to significantly increased survival of the larvae as compared with imipenem or colistin monotherapy alone (p < 0.05).. This is the first report demonstrating the efficacy of antimicrobial agents in the G. mellonella larvae model of infections caused by E. cloacae. Our study suggested that imipenem-colistin combination was highly active against E. cloacae both in vitro and in the simple invertebrate model, and provided preliminary in vivo evidence that such combination might be useful therapeutically.

Topics: Animals; Anti-Bacterial Agents; China; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Imipenem; Larva; Lepidoptera; Microbial Sensitivity Tests; Microbial Viability; Models, Animal; Time Factors

We aimed to characterize carbapenem-resistant isolates in a tertiary hospital in Istanbul, Turkey, high-prevelance area for OXA-48 producers. About 76 Enterobacteriaceae clinical isolates were included. Carbapenemase production was detected by Carbapenem Inactivation Method and carbapenemase genes were investigated by PCR. The clonal relationships were evaluated by AP-PCR. Nineteen Klebsiella pneumoniae isolates were colistin resistant. About 75 isolates yielded carbapenemase by CIM. 52 OXA-48, 17 NDM-1 and 2 VIM-5 carbapenemase genes were detected. Co-production of 'OXA-48 and NDM-1' and 'OXA-48 and VIM-5' were demonstrated in two Klebsiella pneumoniae isolates. The total clustering rate was 20.2%. About 69 Klebsiella pneumoniae yielded 60 profiles and 12 isolates formed five clusters. We have demonstrated the presence of OXA-48 carbapenemases in the majority of isolates in a large collection of carbapenemase-producing isolates from a single hospital. The relatively high rates of NDM-1-producing isolates and colistin resistance is noteworthy.

Topics: Adolescent; Adult; Aged; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Child; Child, Preschool; Colistin; Drug Resistance, Microbial; Endemic Diseases; Enterobacteriaceae Infections; Female; Humans; Infant; Infant, Newborn; Male; Microbial Sensitivity Tests; Middle Aged; Turkey; Young Adult

To study the evolution in the susceptibility of Enterobacter spp. in Crete, Greece from 2010 to 2015.. Non-duplicate isolates were studied using automated systems. Phenotypic confirmatory tests were applied.. A total of 939 Enterobacter isolates were included. Colistin was the most active antibiotic (97.9%) followed by imipenem (96.1%), gentamicin (95.7%), tigecycline (91.8%), cefepime (89.4%), chloramphenicol (85.8%), fosfomycin (85.5%), trimethoprim/sulfamethoxazole (83.3%) and piperacillin/tazobactam (73.3%). Antibiotic resistance did not increase during the study period for most antibiotics. Lower susceptibility was observed among multidrug-resistant strains and carbapenem-nonsusceptible isolates. AmpC was the most common resistant mechanism (21%); carbapenemases (3.7%) and aminoglycoside-modifying enzymes (6.5%) were also detected.. A significant proportion of Enterobacter spp. was resistant to several antibiotics, most notably β-lactams.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Carbapenems; Cefepime; Cephalosporins; Child; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter; Enterobacteriaceae Infections; Greece; Hospitals, University; Humans; Microbial Sensitivity Tests; Minocycline; Penicillanic Acid; Phenotype; Piperacillin; Piperacillin, Tazobactam Drug Combination; Tigecycline

To determine the susceptibility to colistin of Hafnia alvei and Hafnia paralvei, and to compare methods for colistin resistance detection in the Hafnia genus.. A collection of 25 Hafnia isolates was studied. Species were identified by using 16S rRNA gene sequencing with subsequent phylogeny analysis. Susceptibility to colistin was determined using the broth microdilution (BMD) reference method, the Phoenix automated system, the Rapid Polymyxin NP test, the Etest system and the disc diffusion method.. The collection consisted of 15 H. alvei and 10 H. paralvei isolates. Based on the 16S rRNA analysis, a close relationship of the Hafnia genus with naturally colistin-resistant enterobacterial genera (Proteus, Morganella, Providencia and Serratia) was identified. Susceptibility testing performed using the BMD method, the Phoenix automated system and the Rapid Polymyxin NP test revealed a high rate of colistin resistance (96%). Underestimation of colistin resistance using Etest strips (72%) and the disc diffusion method (0%) was observed.. The high rate of colistin resistance observed within the Hafnia genus and its close phylogenetic relationship with naturally colistin-resistant genera suggest that Hafnia is a naturally colistin-resistant enterobacterial genus.

Topics: Anti-Bacterial Agents; Colistin; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Hafnia; Humans; Microbial Sensitivity Tests; Molecular Typing; Phylogeny; RNA, Ribosomal, 16S

In this study, outer membrane proteins (OMPs) of colistin-resistant Klebsiella pneumoniae and Enterobacter asburiae were analyzed. One colistin-susceptible and three colistin-resistant K. pneumoniae sequence type 258 strains as well as one colistin-susceptible E. asburiae and its colistin-heteroresistant counterpart strain were involved in the study. OMP analysis of each strain was performed by microchip method. Matrix-assisted laser desorption ionization time of flight/mass spectrometry (MALDI-TOF/MS) investigation was carried out after separation of OMPs by two-dimensional gel electrophoresis and in-gel digestion. The MALDI-TOF/MS analysis of OMPs in the colistin-susceptible K. pneumoniae found 16 kDa proteins belonging to the LysM domain/BON superfamily, as well as DNA starvation proteins, whereas OmpX and OmpW were detected in the colistin-resistant counterpart strains. OmpC and OmpW were detected in the colistin-susceptible E. asburiae, whereas OmpA and OmpX were identified in the colistin-resistant counterpart. This study demonstrated that OMP differences were between colistin-susceptible and -resistant counterpart strains. The altered Gram-negative cell wall may contribute to acquired colistin resistance in Enterobacteriaceae.

Topics: Bacterial Outer Membrane Proteins; Colistin; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Genes, Bacterial; Humans; Oligonucleotide Array Sequence Analysis; Sequence Analysis, DNA; Time Factors

The emergence of colistin resistance has been detected worldwide in recent years. Whilst colistin susceptibility has been tested in carbapenem resistant Enterobacteriaceae as well as multidrug-resistant Pseudomonas spp. and Acinetobacter spp. during routine laboratory practice, the overall rate of colistin resistance was unknown in our centre. The aim of this retrospective study was to reveal the prevalence of colistin resistance among clinically significant blood culture isolates in two different periods (2010-2011 and 2016) in our laboratory.. Consecutive non-duplicate strains (n=776) were screened for colistin resistance using agar plates containing 4mg/L colistin. Strains cultured on colistin-containing plates were further examined. Minimum inhibitory concentrations (MICs) of colistin-tolerant subcultures and original cultures were determined in parallel by the broth microdilution method. Screening for mcr-1-mediated colistin resistance was performed by PCR.. The rate of colistin resistance was 0.6%, 1.3% and 2.6% in Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp., respectively; colistin-resistant subpopulations were found in 17%, 27% and 20% of isolates, respectively, with low frequency. Seven colistin-resistant strains were found, among which was an mcr-1-positive Escherichia coli isolated from a blood sample of a haemato-oncology patient in 2011. All Stenotrophomonas maltophilia isolates were resistant to colistin.. The low prevalence of colistin resistance was in accordance with European data. The prevalence of heteroresistance was significantly higher, but the clinical significance of the phenomenon is unclear. We have identified the first mcr-1-positive E. coli strain in Hungary. mcr-1 has been in Hungary since 2011 but has not yet expanded.

Topics: Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Hungary; Microbial Sensitivity Tests; Prevalence; Retrospective Studies; Tertiary Care Centers

Topics: Anti-Bacterial Agents; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Fosfomycin; Hong Kong; Humans; Microbial Sensitivity Tests; Penicillins; Public Health Surveillance

The objectives were to determine the prevalence of colistin resistance in clinical isolates of Enterobacteriaceae, and to gain knowledge on the epidemiological and clinical features of the patients.. All colistin-resistant Enterobacteriaceae consecutively isolated from clinical samples in our institution from 2012 to 2015, were included in this cross-sectional study. Intrinsic-resistant species were excluded. Minimum inhibitory concentration was performed by gradient diffusion. Detection of plasmid-encoded colistin resistance genes mcr-1 and mcr-2 was performed by amplification. Epidemiological and clinical features were reviewed.. Of 13579 Enterobacteriaceae isolates, 91 were colistin-resistant. The overall prevalence of colistin resistance was 0.67%. The rates were higher in Enterobacter cloacae (4.2%) than Escherichia coli (0.5%) and Klebsiella pneumoniae (0.4%). One third of the isolates were multi-drug resistant (MDR). While mcr-2 was not detected, mcr-1 was detected only in E. coli. Regarding these infections, 23% were community-acquired. 89% of the patients had not received colistin previously. There were no significant differences between infections caused by mcr-1 and non-mcr-1-carrying isolates.. Colistin resistance was not restricted to MDR isolates and to clinical settings. Most patients had no record of previous administration of colistin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anti-Bacterial Agents; Child; Colistin; Cross-Sectional Studies; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prevalence; Prospective Studies; Retrospective Studies; Spain; Tertiary Care Centers; Young Adult

Colistin is the last drug option for the treatment of MDR Gram-negative bacterial infections. Several types of resistance to colistin have been identified, including hetero-resistance, which has been observed in several Gram-negative pathogens. During a routine surveillance project on antimicrobial resistance, we found abnormal colistin-resistant Enterobacter asburiae and Enterobacter cloacae isolates. E. cloacae is an intestinal commensal bacterium and a well-known opportunistic nosocomial pathogen.. To characterize the molecular mechanism of colistin hetero-resistance in Enterobacter spp.. Several approaches (WGS, transposome mutagenesis and RT-PCR analysis) were used to discover the molecular mechanism of colistin hetero-resistance.. Genomic analysis of mutant clones generated by transposome mutagenesis suggests that hetero-resistance is linked with overexpression of the acrAB-tolC efflux pump. Transcriptional analysis further found that naturally elevated soxRS triggers the induction of the acrAB-tolC efflux pump proteins followed by the development of colistin hetero-resistance in E. asburiae and E. cloacae. Transcriptional analysis results were further verified as demonstrating the development of hetero-resistance in colistin-susceptible strains by plasmid-based overexpression of soxRS.. Our observations highlight the importance of such findings, which previously were only superficially described because of the challenges associated with their detection, in the context of common modes of colistin resistance in Gram-negative bacteria. This study constitutes a unique demonstration of efflux-based high-level colistin hetero-resistance, controlled by a soxRS regulator in Gram-negative bacteria.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Carrier Proteins; Colistin; DNA Transposable Elements; Drug Resistance, Bacterial; Enterobacter; Enterobacter cloacae; Enterobacteriaceae Infections; Gene Expression Regulation, Bacterial; Humans; Microbial Sensitivity Tests; Mutagenesis, Insertional; Transcription Factors

Plazomicin, a novel aminoglycoside with in vitro activity against MDR Gram-negative organisms, is under development to treat patients with serious enterobacterial infections. We evaluated the activity of plazomicin and comparators against colistin-resistant enterobacterial isolates.. Susceptibility to plazomicin and comparators was tested by broth microdilution for a collection of 95 colistin-resistant enterobacterial isolates collected from 29 hospitals in eight countries. Forty-two isolates (Klebsiella pneumoniae and Klebsiella oxytoca) possessed chromosomally encoded resistance mechanisms to colistin, 21 isolates (Escherichia coli and Salmonella enterica) expressed the mcr-1 gene, 8 isolates (Serratia, Proteus, Morganella and Hafnia) were intrinsically resistant to colistin and 24 isolates (K. pneumoniae, E. coli and Enterobacter spp.) had undefined, non-mcr-1 mechanisms. Susceptibility profiles were defined according to CLSI for aminoglycosides and to EUCAST for colistin and tigecycline.. Plazomicin inhibited 89.5% and 93.7% of the colistin-resistant enterobacterial isolates at ≤ 2 and ≤4 mg/L, respectively. MICs of plazomicin were ≤2 mg/L for all of the mcr-1 positive isolates and ≤4 mg/L for all the intrinsic colistin-resistant Enterobacteriaceae. Non-susceptibility to currently marketed aminoglycosides was common: amikacin, 16.8%; gentamicin, 47.4%; and tobramycin, 63.2%. Plazomicin was the most potent aminoglycoside tested with an MIC90 of 4 mg/L, compared with 32, >64 and 64 mg/L for amikacin, gentamicin and tobramycin, respectively.. Plazomicin displayed potent activity against colistin-resistant clinical enterobacterial isolates, including those expressing the mcr-1 gene. Plazomicin was more active than other aminoglycosides against this collection of isolates. The further development of plazomicin for the treatment of infections due to MDR Enterobacteriaceae is warranted.

Topics: Africa; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Colombia; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Proteins; Europe; Humans; Klebsiella oxytoca; Klebsiella pneumoniae; Microbial Sensitivity Tests; Sisomicin

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Hospitals, University; Humans

We described 27 polyclonal colistin-resistant Enterobacteriaceae (MIC 4-16 μg/mL) infections (12 pneumonia, 12 urinary tract infection (UTI), two Bacteremia, and one skin/soft tissue infection) in which 74% harbored KPC. The isolates were polyclonal, 6 STs were identified and the colistin resistance was due to chromosome mutations. Eight patients with UTI received monotherapy, and combination therapy was given to 19 patients. Overall mortality was 37%. In vitro synergy using time-kill assay was observed in 14 of 19 (74%) isolates tested; the synergistic effect was observed for almost all isolates for the combination of three drugs: colistin, amikacin, and tigecycline. The Kaplan-Meier survival curve showed no significant difference comparing combination therapy with 2, 3, or more drugs and risk factors associated with death were dialysis and shock. These findings reinforce the fact that colistin in combination with other classes of drugs can be useful in treating infections caused by colistin-resistant CRE.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Kaplan-Meier Estimate; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Pneumonia; Prospective Studies; Soft Tissue Infections; Tigecycline; Urinary Tract Infections

As part of the multicentre Antibiotic Therapy Optimisation Study, MIC values of 19 non-β-lactam agents were determined for third-generation cephalosporin-resistant Escherichia coli , Klebsiella species and Enterobacter species (3GCREB) isolates collected in German hospitals.. A total of 328 E. coli , 35 Klebsiella spp. (1 Klebsiella oxytoca and 34 Klebsiella pneumoniae ) and 16 Enterobacter spp. (1 Enterobacter aerogenes and 15 Enterobacter cloacae ) isolates were submitted to broth microdilution antimicrobial susceptibility testing with the MICRONAUT system. MICs of fluoroquinolones (levofloxacin and moxifloxacin), aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin and paromomycin), tetracyclines (tetracycline, minocycline and tigecycline), macrolides (erythromycin, clarithromycin and azithromycin) and miscellaneous agents [trimethoprim/sulfamethoxazole, chloramphenicol, nitrofurantoin, colistin and fosfomycin intravenous (iv)] were determined and reviewed against 2016 EUCAST breakpoints.. The MIC of levofloxacin was >2 mg/L for 128 of 328 E. coli and 8 of 35 Klebsiella spp., but only 1 of 16 Enterobacter spp. Rates of resistance to trimethoprim/sulfamethoxazole were high (>70%), except for Enterobacter spp. Rates of resistance to colistin and fosfomycin iv were still low. About 20% of the tested isolates were resistant to chloramphenicol. Only 1 (of 328) E. coli isolate had an MIC of amikacin >16 mg/L and only 33 of 328 E. coli and 1 of 35 Klebsiella spp. had an MIC of tobramycin >4 mg/L, whereas average gentamicin MICs were in general more elevated. A tigecycline MIC >2 mg/L was only found for 1 of 16 Enterobacter spp., but in none of the E. coli or Klebsiella spp. isolates.. Our study gives insight into previously unreported non-β-lactam MIC distributions of 3GCREB isolates.

Topics: Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cephalosporin Resistance; Cephalosporins; Colistin; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; Escherichia coli; Hospitalization; Humans; Klebsiella; Microbial Sensitivity Tests; Minocycline; Tertiary Care Centers; Tetracycline; Tigecycline

The mcr-1 gene confers transferable colistin resistance. mcr-1-positive Enterobacteriaceae (MCRPE) have attracted substantial medical, media, and political attention; however, so far studies have not addressed their clinical impact. Herein, we report the prevalence of MCRPE in human infections and carriage, clinical associations of mcr-1-positive Escherichia coli (MCRPEC) infection, and risk factors for MCRPEC carriage.. We undertook this study at two hospitals in Zhejiang and Guangdong, China. We did a retrospective cross-sectional assessment of prevalence of MCRPE infection from isolates of Gram-negative bacteria collected at the hospitals from 2007 to 2015 (prevalence study). We did a retrospective case-control study of risk factors for infection and mortality after infection, using all MCRPEC from infection isolates and a random sample of mcr-1-negative E coli infections from the retrospective collection between 2012 and 2015 (infection study). We also did a prospective case-control study to assess risk factors for carriage of MCRPEC in rectal swabs from inpatients with MCRPEC and mcr-1 negative at the hospitals and collected between May and December, 2015, compared with mcr-1-negative isolates from rectal swabs of inpatients (colonisation study). Strains were analysed for antibiotic resistance, plasmid typing, and transfer analysis, and strain relatedness.. We identified 21 621 non-duplicate isolates of Enterobacteriaceae, Acinetobacter spp, and Pseudomonas aeruginosa from 18 698 inpatients and 2923 healthy volunteers. Of 17 498 isolates associated with infection, mcr-1 was detected in 76 (1%) of 5332 E coli isolates, 13 (<1%) of 348 Klebsiella pneumoniae, one (<1%) of 890 Enterobacter cloacae, and one (1%) of 162 Enterobacter aerogenes. For the infection study, we included 76 mcr-1-positive clinical E coli isolates and 508 mcr-1-negative isolates. Overall, MCRPEC infection was associated with male sex (209 [41%] vs 47 [63%], adjusted p=0·011), immunosuppression (30 [6%] vs 11 [15%], adjusted p=0·011), and antibiotic use, particularly carbapenems (45 [9%] vs 18 [24%], adjusted p=0·002) and fluoroquinolones (95 [19%] vs 23 [30%], adjusted p=0·017), before hospital admission. For the colonisation study, we screened 2923 rectal swabs from healthy volunteers, of which 19 were MCRPEC, and 1200 rectal swabs from patients, of which 35 were MCRPEC. Antibiotic use before hospital admission (p<0·0001) was associated with MCRPEC carriage in 35 patients compared with 378 patients with mcr-1-negative E coli colonisation, whereas living next to a farm was associated with mcr-1-negative E coli colonisation (p=0·03, univariate test). mcr-1 could be transferred between bacteria at high frequencies (10. In 2017, colistin will be formally banned from animal feeds in China and switched to human therapy. Infection with MRCPEC is associated with sex, immunosuppression, and previous antibiotic exposure, while colonisation is also associated with antibiotic exposure. MLST and plasmid analysis shows that MCRPEC are diversely spread throughout China and pervasive in Chinese communities.. National Key Basic Research Program of China, National Natural Science Foundation of China/Zhejiang, National Key Research and Development Program, and MRC, UK.

Topics: Animals; Carbapenems; Case-Control Studies; China; Colistin; Cross-Sectional Studies; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Healthy Volunteers; Humans; Molecular Epidemiology; Plasmids; Prevalence; Prospective Studies; Retrospective Studies; Risk Factors; Sex Factors

Topics: Anti-Bacterial Agents; beta-Lactamases; CD4 Lymphocyte Count; Cephalosporins; Cohort Studies; Colistin; Drug Resistance, Multiple, Bacterial; Dysbiosis; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Proteins; Feces; HIV Infections; Humans; Intestines; Microbial Sensitivity Tests; Microbiota; Plasmids; Risk Factors; Switzerland

Four NDM-1-producing Enterobacteriaceae strains (three Klebsiella pneumoniae and one Citrobacter koseri) were isolated between 2009 and 2011 through a nationwide surveillance for carbapenem-resistant Enterobacteriaceae in Croatia to study the molecular genetic background of blaNDM and the responsible plasmid types. Phenotypically, the clinical strains proved to be multidrug resistant. All strains remained susceptible to tigecycline and colistin. The clinical strains harbored variable antibiotic resistance determinants, notably, blaNDM-1, blaTEM-1, blaSHV-1, blaSHV-12, blaOXA-1, blaOXA-9, blaCTX-M-15, blaCMY-4, qnrB1, and aac(6')Ib-cr in different combinations. Two K. pneumoniae belonged to sequence type ST15 and one strain to ST16. As for the plasmid types, C. koseri and one of the ST15 K. pneumoniae carried IncR, and the second ST15 K. pneumoniae carried IncR and colE. The K. pneumoniae ST16 strain hosted A/C and colE plasmids. The blaNDM-1 gene was detected on conjugative high-molecular-weight plasmids, namely, A/C and IncR types. It is noteworthy that this is the first description of K. pneumoniae ST16 expressing NDM-1 in Europe. Remarkably, our study underscores the importance of the IncR plasmid as a reservoir of multidrug resistance. To the best of our knowledge, the IncR plasmid carrying blaNDM-1 in C. koseri is reported for the first time.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Citrobacter koseri; Colistin; Conjugation, Genetic; Croatia; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Gene Expression; Gene Transfer, Horizontal; Humans; Isoenzymes; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Plasmids; Sequence Analysis, DNA; Tigecycline

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Middle Aged; Practice Guidelines as Topic; Tertiary Care Centers

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae.. The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model.. Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10(-1) to 10(-3) cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011-14, and 16 (1%) of 1322 samples from inpatients with infection.. The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria.. Ministry of Science and Technology of China, National Natural Science Foundation of China.

Topics: Animals; China; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Meat; Mice; Plasmids; Polymyxins; Swine; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Abdominal Injuries; Coinfection; Colistin; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Intestinal Perforation; Intestine, Small; Male; Middle Aged; Peritonitis; Phylogeny; Pneumoperitoneum; Ribotyping; RNA, Bacterial; RNA, Ribosomal, 16S; Sequence Alignment; Sequence Homology, Nucleic Acid; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Wounds, Nonpenetrating

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

Topics: Animals; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Polymyxins; Swine Diseases

In response to the first report of transmissible colistin resistance mediated by the mcr-1 gene in Escherichia coli and Klebsiella spp. from animals and humans in China, we sought to determine its presence in Enterobacteriaceae isolated in the UK.. The PHE archive of whole-genome sequences of isolates from surveillance collections, submissions to reference services and research projects was retrospectively analysed for the presence of mcr-1 using Genefinder. The genetic environment of the gene was also analysed.. Rapid screening of the genomes of ∼24 000 Salmonella enterica, E. coli, Klebsiella spp., Enterobacter spp., Campylobacter spp. and Shigella spp. isolated from food or humans identified 15 mcr-1-positive isolates. These comprised: 10 human S. enterica isolates submitted between 2012 and 2015 (8 Salmonella Typhimurium, 1 Salmonella Paratyphi B var Java and 1 Salmonella Virchow) from 10 patients; 3 isolates of E. coli from 2 patients; and 2 isolates of Salmonella Paratyphi B var Java from poultry meat imported from the EU. The mcr-1 gene was located on diverse plasmids belonging to the IncHI2, IncI2 and IncX4 replicon types and its association with ISApl1 varied. Six mcr-1-positive S. enterica isolates were from patients who had recently travelled to Asia.. Analysis of WGS data allowed rapid confirmation of the presence of the plasmid-mediated colistin resistance gene mcr-1 in diverse genetic environments and plasmids. It has been present in E. coli and Salmonella spp. harboured by humans in England and Wales since at least 2012.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Computational Biology; Drug Resistance, Bacterial; England; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Food Microbiology; Genes, Bacterial; Humans; Male; Middle Aged; Plasmids; Retrospective Studies; Sequence Analysis, DNA; Wales; Young Adult

Stool samples from 38 travelers returning from India were screened for extended-spectrum cephalosporin- and carbapenem-resistant Enterobacteriaceae implementing standard selective plates. Twenty-six (76.3%) people were colonized with CTX-M or DHA producers, but none of the strains was colistin resistant and/or mcr-1 positive. Nevertheless, using overnight enrichment and CHROMagar Orientation plates supplemented with colistin, four people (10.5%) were found to be colonized with colistin-resistant Escherichia coli One cephalosporin-susceptible sequence type 10 (ST10) strain carried a 4,211-bp ISApl1-mcr-1-ISApl1 element in an IncHI2 plasmid backbone.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; India; Plasmids

The aim of the study was to investigate the prevalence of extended-spectrum β-lactamase (ESBL) and carbapenemase production among clinical isolates of Enterobacteriaceae recovered from Tunisian and Libyan hospitals.. Bacterial isolates were recovered from patients in intensive care units and identified by biochemical tests and MALDI-TOF. Antibiotic susceptibility testing was performed by disk diffusion and the E-test method. ESBL and carbapenemase activities were detected using standard microbiological tests. Antibiotic resistance-encoding genes were screened by PCR and sequencing. Clonal relationships between Klebsiella pneumoniae strains were carried out using multi-locus sequence typing (MLST).. A total of 87 isolates were characterized, with 51 and 36, respectively, identified as E. coli and K. pneumoniae. Overall the resistance prevalence was high for aminoglycosides (> 60%), fluoroquinolones (> 80%), and extended-spectrum cephalosporins (> 94%), and was low for imipenem (11.4%). Among this collection, 58 strains (66.6%) were ESBL producers and 10 K. pneumoniae strains (11.4%) were carbapenemase producers. The antibiotic resistance-encoding genes detected were blaCTX-M-15 (51.7%), blaTEM-1 (35.6%), several variants of blaSHV (21.8%), and blaOXA-48 (11.4%). The MLST typing of K. pneumoniae isolates revealed the presence of multiple clones and three novel sequence types. Also, close relationships between the OXA-48-producing strains from Tunisia and Libya were demonstrated.. This study is the first paper describing the emergence of carbapenemase- and ESBL-producing Enterobacteriaceae, sensitive to colistin, isolated in Tunisia and Libya. Active surveillance and testing for susceptibility to colistin should be implementing because resistance to colistin, mainly in Klebsiella, has been recently reported worldwide.

Topics: Anti-Bacterial Agents; Bacterial Typing Techniques; beta-Lactamases; Colistin; Cross Infection; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Escherichia coli; Genotype; Hospitals; Humans; Intensive Care Units; Klebsiella pneumoniae; Libya; Microbial Sensitivity Tests; Multilocus Sequence Typing; Polymerase Chain Reaction; Prevalence; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tunisia

Aims of this study were to: (i) evaluate whether the cluster membership could have an impact on hetero-resistance phenotype to colistin in the Enterobacter cloacae complex (ECC); and (ii) determine the genetic mechanism of colistin hetero-resistance in ECC.. A collection of 124 clinical isolates belonging to 13 clusters were used to analyse the hetero-resistance phenotype (MICs were determined using the broth microdilution method, Etest and population analysis profiling). Different mutants (ΔphoP, ΔphoQ, ΔphoPQ, ΔpmrA, ΔpmrB, ΔpmrAB, ΔarnE, ΔarnF and ΔarnBCADTEF) were constructed and tested for their colistin hetero-resistance phenotype.. Because the colistin hetero-resistance appeared cluster-dependent in the ECC, it should be advocated to determine the cluster of the strain associated with the infection in parallel with the MIC of colistin. The resistance mechanism may not be similar to other Enterobacteriaceae since only the two-component regulatory system PhoP/PhoQ (and not PmrA/PmrB) seemed to play a role in resistance regulation.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Gene Deletion; Genes, Bacterial; Genotype; Humans; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenem-Resistant Enterobacteriaceae; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Pneumonia, Ventilator-Associated

Topics: Anti-Bacterial Agents; Bacteremia; Bacteriological Techniques; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Mass Screening; Plasmids

Topics: Anti-Bacterial Agents; Carbapenems; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Plasmids; Singapore; Urine

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Genes, Bacterial; Hong Kong; Humans; Microbial Sensitivity Tests; Population Surveillance; Real-Time Polymerase Chain Reaction; Sequence Analysis, DNA

Antibiotic resistance is a major public health threat, further complicated by unexplained treatment failures caused by bacteria that appear antibiotic susceptible. We describe an Enterobacter cloacae isolate harbouring a minor subpopulation that is highly resistant to the last-line antibiotic colistin. This subpopulation was distinct from persisters, became predominant in colistin, returned to baseline after colistin removal and was dependent on the histidine kinase PhoQ. During murine infection, but in the absence of colistin, innate immune defences led to an increased frequency of the resistant subpopulation, leading to inefficacy of subsequent colistin therapy. An isolate with a lower-frequency colistin-resistant subpopulation similarly caused treatment failure but was misclassified as susceptible by current diagnostics once cultured outside the host. These data demonstrate the ability of low-frequency bacterial subpopulations to contribute to clinically relevant antibiotic resistance, elucidating an enigmatic cause of antibiotic treatment failure and highlighting the critical need for more sensitive diagnostics.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Histidine Kinase; Immunity, Innate; Mice; Treatment Failure

The newly identified plasmid-borne colistin resistance gene mcr-1 was found in a Kluyvera ascorbata isolate from hospital sewage in China. mcr-1 was carried by a 57-kb self-transmissible IncI2 plasmid. Unlike in a previous report, mcr-1 was not associated with ISApl1 and was inserted into a gene encoding a putative membrane protein by an unknown mechanism. This study highlights that mcr-1 has spread to multiple bacterial species.

Topics: Anti-Bacterial Agents; China; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Gene Expression; Genes, Bacterial; Hospitals; Humans; Kluyvera; Membrane Proteins; Microbial Sensitivity Tests; Mutagenesis, Insertional; Plasmids; Sewage

From January 2014 to December 2014, 972 consecutive non-replicate carbapenemase-producing Enterobacteriaceae isolates from colonised or infected patients were collected at the Associated French National Reference Centre as part of the French national survey on antimicrobial resistance. It included 577 Klebsiella spp. (59%), 236 Escherichia coli (24%), 108 Enterobacter spp. (11%), 50 Citrobacter spp. (5%), and a single Salmonella spp. isolate (0.1%). Of 561 K. pneumoniae isolates, 35 were found to be resistant to colistin (6.2%). PFGE analysis revealed a clonal outbreak involving 15 K. pneumoniae isolates belonging to sequence type ST11, recovered in a single hospital in the Picardie region in northern France. Those clonally related isolates showed variable levels of resistance to colistin, ranging from 4 to 64 mg/L. They harboured the blaOXA-48 carbapenemase gene and the blaCTX-M-15 extended-spectrum beta-lactamase gene. Among the 91 Enterobacter cloacae isolates, seven were resistant to colistin and produced different types of carbapenemases. Surprisingly, none of the E. coli and Citrobacter spp. isolates showed resistance to colistin. This national survey including carbapenemase-producing isolates recovered in 2014 reported a high rate of colistin resistance in K. pneumoniae and E. cloacae (6.2% and 7.7%, respectively) in France.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Disease Outbreaks; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae; Enterobacteriaceae Infections; France; Genotype; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Retrospective Studies; Sequence Analysis, DNA; Surveys and Questionnaires

To describe the clinical and microbiological data of carbapenem-resistant Enterobacteriaceae (CRE) infections, the treatment used, hospital- and infection-related mortality, and risk factors for death.. A prospective cohort conducted from March 2011 to December 2012. Clinical, demographic, and microbiological data such as in vitro sensitivity, clonality, carbapenemase gene mortality related to infection, and overall mortality were evaluated. Data were analyzed using Epi Info version 7.0 (CDC, Atlanta, GA, USA) and SPSS (Chicago, IL, USA).. One hundred and twenty-seven patients were evaluated. Pneumonia, 52 (42 %), and urinary tract infections (UTI), 51 (40.2 %), were the most frequent sites of infection. The isolates were polyclonal; the Bla. CRE infection mortality was higher among patients with pneumonia. Infections caused by colistin-resistant isolates did not increase mortality. The use of more than two drugs on combination therapy did not show a protective effect on outcome. The isolates were polyclonal, and the bla

Topics: Adult; Age Factors; Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cohort Studies; Colistin; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Hospital Mortality; Humans; Kidney Failure, Chronic; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Polymerase Chain Reaction; Prospective Studies; Renal Dialysis; Risk Factors; Shock, Septic; Urinary Tract Infections

The widespread multidrug-resistant Enterobacteriaceae pose a serious therapeutic challenge. Colistin and tigecycline are potential antimicrobial agents for treating infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. We evaluated the in-vitro activity of colistin sulfate against 253 ESBL producers isolated from patients admitted to a medical center in southern Taiwan (Escherichia coli, n = 82; Klebsiella pneumoniae, n = 102; Enterobacter cloacae, n = 34; and Serratia marcescens, n = 35). Colistin showed promising in-vitro activity against E. coli, K. pneumoniae, and E. cloacae, but not S. marcescens. One ESBL-producing K. pneumoniae strain with resistance to carbapenems (ertapenem, imipenem, and meropenem) was selected for time-killing studies. A combination of colistin and tigecycline showed synergism, but there was an inoculum effect. In conclusion, colistin was active against most ESBL-producing Enterobacteriaceae, and a combination of colistin with tigecycline was synergistic against some highly resistant strains, even those with carbapenem resistance.

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Enterobacter cloacae; Enterobacteriaceae Infections; Escherichia coli; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Serratia marcescens; Tigecycline

Topics: Anti-Bacterial Agents; beta-Lactamases; Coinfection; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Pyoderma; Skin Transplantation; Staphylococcal Infections

Carbapenemase-producing Enterobacteriaceae (CPE) cause serious infections and are associated with high mortality in part due to limited treatment options. The in vitro activities of the new aminoglycoside plazomicin and comparators were evaluated against a collection of 164 CPE (VIM-1, n=125; KPC-2, n=34; OXA-48, n=4; and IMP-22, n=1). MIC90 values of gentamicin, tobramycin and amikacin were 256, 64 and 16 mg/L, respectively. Plazomicin exhibited an MIC range of 0.12-4 mg/L with MIC50 and MIC90 values of 0.25 and 1 mg/L. The MICs of plazomicin did not correlate with the other aminoglycoside MICs, with the resistance phenotype or with the carbapenemase harboured. Chequerboard experiments against 10 carbapenemase-producing Klebsiella pneumoniae isolates showed that combinations of plazomicin with colistin yielded synergy against 60% of the strains. Synergy of plazomicin with meropenem or fosfomycin was detected against 20% and 25% of the isolates, respectively. Using time-kill methodology, the interactions of plazomicin at 2×, 1× and 0.5× MIC with meropenem, colistin, fosfomycin or tigecycline at steady-state concentrations against two K. pneumoniae carrying the VIM-1 enzyme were investigated. Bactericidal activity was evident for both isolates at 2× MIC of plazomicin. Synergy was observed when plazomicin was combined with meropenem, colistin or fosfomycin against both isolates, whilst the combination with tigecycline resulted in indifference. Antagonism was not observed for any of the combinations tested. The results of this study suggest that plazomicin may address the need for new therapeutic options for the treatment of infections due to CPE.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Fosfomycin; Humans; Klebsiella oxytoca; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Minocycline; Serratia marcescens; Sisomicin; Thienamycins; Tigecycline

Multidrug-resistant Escherichia coli and other enteric bacteria producing extended-spectrum β-lactamases (ESBL) have emerged as an important cause of invasive infection. Targeting the primary (intestinal) niche by decolonization may be a valuable approach to decrease the risk of relapsing infections and to reduce transmission of ESBL-producing enteric pathogens.. In a retrospective observational study we evaluated the efficacy of intestinal decolonization treatment using orally administered colistin or other non-absorbable agents given for 2 to 4 weeks in adult patients with previous relapsing infection and persistent intestinal colonization with ESBL-positive Enterobacteriaceae (ESBL-E). Eradication success was defined as negative rectal swab or stool culture at the end of treatment and at follow up-2 weeks after treatment discontinuation.. First-line decolonization treatment led to eradication of ESBL-E in 19/45 patients (42%, 7/18 low-dose [4 × 1 million units] colistin, 3/12 high-dose [4 × 2 million units] colistin, 9/15 rifaximin [2 × 400 mg]), and secondary/salvage treatment was successful in 8/13 patients (62 %, 20 treatment episodes). Late follow-up showed that 7/13 patients (54%) with successful initial or salvage decolonization became recolonized within 3 months after post-treatment assessment while all eight of the patients failing initial or salvage decolonization treatment with late follow-up remained colonized. A narrative review of the literature confirms the limited efficacy of non-absorbable antibiotics including conventional selective digestive tract decolonization (SDD)-like combination regimens for eradicating multidrug-resistant enteric bacteria from the intestinal tract.. At present, there is no clear evidence of a significant decolonization efficacy using single-drug treatment with oral non-absorbable antibiotics. More effective regimens are needed and a better definition of at risk patients is required for planning meaningful randomized controlled studies in this field.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Gastrointestinal Microbiome; Humans; Intestines; Male; Middle Aged; Retrospective Studies; Rifamycins; Rifaximin; Treatment Outcome; Young Adult

Carbapenem resistance among the Enterobacteriaceae is a serious healthcare challenge. bla IMI is a carbapenemase gene mediating resistance to carbapenems but has not been commonly found. A bla IMI-carrying Enterobacter cloacae, which was also resistant to colistin, is reported here.. E. cloacae strain WCHECl-1060 was recovered from a blood sample of a leukemia patient, who was not previously exposed to colistin. Strain WCHECl-1060 belongs to a new sequence type, ST410, and was resistant to carbapenems and colistin but was susceptible to third-generation cephalosporins. A new allelic variant of bla IMI-1, which has two silent mutations compared to the original bla IMI-1 variant, was found in strain WCHECl-1060. Conjugation and transformation experiments failed to transfer bla IMI-1, suggesting a likely chromosome origin.. To our knowledge, this is the first report of an IMI-1 carbapenemase-producing colistin-resistant E. cloacae in China. Microbiological laboratories should be aware of the unusual carbapenem-resistant but third-generation cephalosporin-susceptible profiles of these IMI-producing isolates. The trend of colistin resistance among the Enterobacteriaceae should be also monitored.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; China; Colistin; Conjugation, Genetic; DNA, Bacterial; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Leukemia; Male; Molecular Sequence Data; Molecular Typing; Sequence Analysis, DNA

The increasing use of carbapenems for treating multidrug-resistant (MDR) Gram-negative bacterial infections has contributed to the global dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Serine and metallo-β-lactamases (MBLs) that hydrolyze carbapenems have become prevalent and endemic in some countries, necessitating the use of older classes of agents, such as colistin. A total of 19,719 isolates of Enterobacteriaceae (excluding Proteeae and Serratia spp., which have innate resistance to colistin) were collected from infected patients during 2012 and 2013 in a global surveillance program and tested for antimicrobial susceptibility using CLSI methods. Isolates of CRE were characterized for carbapenemases and extended-spectrum β-lactamases (ESBLs) by PCR and sequencing. Using EUCAST breakpoints, the rate of colistin susceptibility was 98.4% overall, but it was reduced to 88.0% among 482 carbapenemase-positive isolates. Colistin susceptibility was higher among MBL-positive isolates (92.6%) than those positive for a KPC (87.9%) or OXA-48 (84.2%). Of the agents tested, only tigecycline (MIC90, 2 to 4 μg/ml) and aztreonam-avibactam (MIC90, 0.5 to 1 μg/ml) consistently tested with low MIC values against colistin-resistant, ESBL-positive, and carbapenemase-positive isolates. Among the 309 (1.6%) colistin-resistant isolates from 10 species collected in 38 countries, 58 carried a carbapenemase that included KPCs (38 isolates), MBLs (6 isolates), and OXA-48 (12 isolates). These isolates were distributed globally (16 countries), and 95% were Klebsiella pneumoniae. Thirty-nine (67.2%) isolates carried additional ESBL variants of CTX-M, SHV, and VEB. This sample of Enterobacteriaceae demonstrated a low prevalence of colistin resistance overall. However, the wide geographic dispersion of colistin resistance within diverse genus and species groups and the higher incidence observed among carbapenemase-producing MDR pathogens are concerning.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests

In this study susceptibility to different antimicrobial peptides was investigated on colistin-susceptible and colistin-resistant identical pulsotype strains of KPC-2 producing Klebsiella pneumoniae ST258 as well as colistin-susceptible and colistin-resistant Enterobacter asburiae strains isolated from clinical samples. In our test, bacteria were exposed to 50 mg/ml lactoferrin, lysozyme and protamine - cationic antimicrobial peptides belonging to innate immune system and having structural similarity to polymyxins - in separate reactions. After 18 hours incubation of colonies were counted. 40% of colistin-resistant K. pneumoniae strains and 97% of colistin-susceptible counterpart strains were lysed by protamine whereas 87% and 100% colony forming unit decrease by lysozyme was seen, respectively. In the case of colistin-resistant E. asburiae strains 1 log10 cell count increase were observed after treatment with lysozyme and 1.56 log10 after lactoferrin exposure compared to the initial number whereas the colistin-susceptible showed no relevant cell count increase. Our findings suggest that acquired colistin-resistance in Enterobacteriaceae is associated with tolerance against antimicrobial peptides.

Topics: Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Colistin; Drug Resistance, Bacterial; Enterobacter; Enterobacteriaceae Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

We present a case of post-neurosurgical ventriculitis caused by carbapenemase-producing Enterobacter cloacae successfully treated with intraventricular colistin. Enterobacter spp are intrinsically resistant to aminopenicillins, cefazolin, and cefoxitin due to the production of constitutive chromosomal AmpC beta-lactamases. Moreover, extended-spectrum beta-lactamase-producing Enterobacter spp have been identified in the USA and Europe, and carbapenems are considered the drug of choice in these cases. Our isolate was sensitive only to fosfomycin, tigecycline, and colistin, and 6 days of intravenous colistin had failed to eradicate the infection. This case provides clinical evidence to support the administration of intraventricular colistin in such patients.

Topics: Administration, Intravenous; Amikacin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Ceftazidime; Cerebral Ventriculitis; Child, Preschool; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Male; Teicoplanin; Treatment Outcome

Five carbapenem-resistant strains (three Klebsiella pneumoniae, one Escherichia coli, and one Enterobacter aerogenes) were isolated between 2009 and 2012 at the Verona University Hospital, Italy, during an epidemiological analysis of antibiotic resistance determinants and plasmid profiles in Enterobacteriaceae. Two out of the five strains, K. pneumoniae E530 and E. coli E558, were cultured from bile and abdominal drainage, respectively, of a single patient. The strains were resistant to beta-lactams and fluoroquinolones, and susceptible to tigecycline and colistin. All the strains harboured bla(KPC-3), bla(TEM-1), and bla(OXA-9), and the three K. pneumoniae additionally carried blaSHV-11 and aac(6')Ib. The bla(KPC-3) was inserted in transposon Tn4401a. All the strains hosted an FIIk-type plasmid, and the three K. pneumoniae coharboured an colE-type plasmid. Transconjugants, besides bla(KPC-3), harboured bla(TEM-1) and bla(OXA-9) genes on FIIk-type plasmid. K. pneumoniae E301 was ST258, while strain E530 and C525 belonged to the ST512, and E. coli E558 was ST43. To our best knowledge, this is the first report that strongly supports the transmission of bla(KPC-3) from ST512 K. pneumoniae to E. coli ST43 in a single patient, a phenomenon of both clinical and microbiological importance.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Bile; Colistin; Conjugation, Genetic; DNA Transposable Elements; Drug Resistance, Multiple, Bacterial; Enterobacter aerogenes; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Gene Expression; Humans; Klebsiella Infections; Klebsiella pneumoniae; Minocycline; Plasmids; Tigecycline

Here we describe the carbapenemase genes, genetic relatedness and antimicrobial susceptibility data of 123 carbapenemase-producing Enterobacteriaceae (CPE) clinical isolates recovered from 2010 to 2012, comprising Klebsiella pneumoniae (n = 79), Klebsiella oxytoca (n = 13), Serratia marcescens (n = 14), Enterobacter cloacae (n = 12), Enterobacter asburiae (n = 4) and Enterobacter aerogenes (n = 1). VIM-1 was the most common carbapenemase (n = 101) followed by KPC-2 (n = 19), OXA-48 (n = 2) and IMP-22 (n = 1). Among the K. pneumoniae isolates, nine sequence types (STs) were identified but two clones were dominant: ST11 (54/79) containing mainly VIM-1-producing isolates; and ST101 (13/79) constituted by KPC-2-producing strains. Pulsed-field gel electrophoresis (PFGE) showed a higher genetic diversity among the remaining Enterobacteriaceae. Amikacin and fosfomycin were the most active agents with 82.9% and 80.5% susceptibility, respectively. Non-susceptibility to tigecycline was detected in 36.5% of strains. Overall, colistin resistance was 24.7% and was as high as 47% in Enterobacter spp. An increase in colistin resistance from 13.5% to 31.7% was observed among K. pneumoniae isolates during the study period. Resistance was focused on ST11 since 83.3% of colistin-resistant strains belonged to this clone. The high level of colistin resistance observed in this study is worrying with respect to the already limited therapeutic options for infections caused by multidrug-resistant Gram-negative bacteria.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Spain; Tertiary Care Centers

We assessed the activity of tigecycline (TGC) combined with colistin (COL) against carbapenem-resistant enterobacteria. Synergy occurred in vitro against the majority of isolates, with the exception of Serratia marcescens. In a simple animal model (Galleria mellonella), TGC-COL was superior (P < 0.01) in treating Escherichia coli, Klebsiella pneumoniae, and Enterobacter infections, including those with TGC-COL resistance. Clinical studies are needed to determine whether TGC-COL regimens may be a viable option.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Colistin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Minocycline; Moths; Tigecycline

Emergence of carbapenem-resistant Enterobacteriaceae has become a substantial global health problem. The aim of this study was to analyze carbapenem-resistant isolates of Enterobacter cloacae that have emerged for the first time in the intensive care unit (ICU) at the University Hospital Centre Split, Croatia. The strains were selected in the period between June and August 2012, according to their susceptibility patterns to carbapenems. Resistant isolates were screened for metallo-β-lactamase (MBL) production with the use of the imipenem-EDTA disk synergy test, and positive findings were confirmed by PCR. The type of VIM β-lactamase gene was determined by sequencing of PCR products. The genetic relatedness was evaluated using pulsed-field gel electrophoresis analysis. The demographic and clinical data were retrospectively analyzed from medical records. Five patients were infected and one patient was colonized with a single clone of multidrug-resistant VIM-1-producing E. cloacae susceptible only to colistin. Three cases of lower respiratory tract infections, one case of bacteremia, and one case of intra-abdominal infection were identified. All cases were hospital-acquired after prolonged stay in ICU. All patients had serious underlying diseases and received a broad-spectrum antibiotic. Four patients died and two had unimprovable medical condition at the time of discharge from the hospital. MBL-producing E. cloacae can cause fatal infection in severely ill patients. Monoclonal outbreak highlights the need for continuous surveillance and good infection control practices to prevent further spread since the antibiotic therapy options for infections caused by such strains are strongly limited.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Clone Cells; Colistin; Critical Illness; Croatia; Cross Infection; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Gene Expression; Hospitals, University; Humans; Intensive Care Units; Male; Microbial Sensitivity Tests; Middle Aged; Survival Analysis

The objective of this investigation was to evaluate the association between colistin consumption and the isolation of intrinsically resistant to colistin Enterobacteriaceae (IRCE) in a university hospital in Crete, Greece. The database of the microbiological laboratory was reviewed retrospectively during 2006-2010. All positive cultures for IRCE were retrieved. We assessed the total consumption of colistin in medical, surgical, and intensive care units (ICUs). A total of 1,304 single-patient IRCE isolates were recorded. Of these, 466 (35.7%) were hospital-acquired, while 838 (64.3%) were community-acquired. Proteus spp. accounted for 72% of them, Serratia spp. for 16.6%, Morganella morganii for 8.4%, and Providencia spp. for 3%. Urine (44.8%), pus (20.4%), and lower respiratory tract specimens (12.8%) accounted for the majority of specimens. IRCE isolated during the first half (2006 to 1st semester of 2008) and second half (2nd semester of 2008 to 2010) of the study period accounted for 5.8% and 7.4% of Gram-negative isolates, respectively (p < 0.001). Colistin consumption was not different in the two periods in the hospital, but in the ICU, it was higher in the second half of the study period (p = 0.013). Colistin consumption was associated with the isolation of hospital-acquired IRCE (p = 0.037); a trend was noted between colistin consumption and the isolation of IRCE in the ICU (p = 0.057). In this study, colistin consumption was associated with the isolation of hospital-acquired IRCE. The use of colistin increased in the ICU during the study period. Prudent use of colistin is essential for the prevention of nosocomial outbreaks due to resistant IRCE.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Drug Utilization; Enterobacteriaceae; Enterobacteriaceae Infections; Greece; Humans; Retrospective Studies; Tertiary Care Centers

Prosthetic joint infections are severe complications of joint implants. Further complications arise when polymicrobial and/or multidrug-resistant microorganisms are involved. Currently, there are limited data on the management of these infections and on the tolerability of long-term treatment with daptomycin, ceftazidime and colistin.. A 55-year-old Caucasian woman who had a right hip prosthesis removed 1 year prior because of infection was admitted for prosthesis reimplantation. On admission at our hospital, anamnesis regarding etiology and management of prosthesis infection was not available. On clinical, laboratory findings and imaging studies infection was not suspected. A hip prosthesis was reimplanted. At surgery, histopathological and microbiological investigations were not taken. Three weeks after reimplantation, surgical site infection due to Enterobacter cloacae was diagnosed and oral ciprofloxacin was prescribed. Four days later, a periprosthesis fluid collection was evidenced and a percutaneous needle aspirate grew Staphylococcus epidermidis and S. haemolyticus. Enterobacter genome was also detected from the same sample. Teicoplanin and meropenem were added to ciprofloxacin without clinical improvement. Moreover, acetabular cup dislocation was documented. She underwent prosthesis explantation, debridement, and positioning of an antimicrobial mixed spacer. From the intraoperatory cultures S. epidermidis and Acinetobacter baumannii were grown. Daptomycin, ceftazidime, colistin and rifampin were administered. Four days later, rifampin was stopped due to a suspected liver toxicity. While undergoing therapy she presented recurrent episodes of wound dehiscence and on the 22nd week of treatment a further surgical debridement was performed, upon which the spacer was removed. At this time, intraoperative cultures resulted negative. Three months later, after a total of 8 months, antimicrobials were interrupted. Subsequently, a femoral transcondylar traction was positioned, and 3 weeks later a new prosthesis was reimplanted. At over 1 year after reimplantation she is well.. Our findings suggest that microbiologic investigations are mandatory even when prosthetic joint infection is not suspected. Molecular methods for identification of microorganisms can be used in addition to conventional cultures especially when patients are under antibiotic treatment. Daptomycin, ceftazidime and colistin can be administered for several months without side effects. Guidelines specifically addressing the diagnosis and the management of polymicrobial, multidrug-resistant prosthetic joint infections need to be developed.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Ceftazidime; Coinfection; Colistin; Daptomycin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacter cloacae; Enterobacteriaceae Infections; Female; Hip Prosthesis; Humans; Middle Aged; Prosthesis-Related Infections; Recurrence; Reoperation; Staphylococcal Infections; Staphylococcus epidermidis; Staphylococcus haemolyticus; Treatment Outcome

Blood stream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) are associated with high hospital mortality rates and present a tremendous challenge to clinicians. The optimal treatment remains undefined. We aimed to investigate the risk factors for mortality and the correlation between different treatment modalities and outcomes.. The clinical characteristics and treatment outcomes of a cohort of 36 patients with BSIs due to CRE were investigated and a retrospective nested case-control study of surviving and non-surviving patients was conducted.. Fifty percent of the cases were male and the mean patient age was 54.9 ± 15.8 years. Klebsiella pneumoniae was the etiological agent in 26 cases (72.2%), Escherichia coli in eight (22.2%), and Enterobacter aerogenes in two (5.5%). All strains were phenotypically positive for carbapenemase activity and all except two (one E. coli and one K. pneumoniae) yielded both blaOXA-48 carbapenemases and blaCTX-M-type extended-spectrum beta-lactamases (ESBLs) in PCR products. The 14-day, 28-day, and all-cause in-hospital mortality rates were 41.6%, 50%, and 58.3%, respectively. The median time to death was 8 days (range 2-52 days). No significant differences were observed between survivors and non-survivors in terms of baseline characteristics, comorbid conditions, etiologies, or sources of bacteremia, however hematological malignancies (p=0.015) and prolonged neutropenia (p=0.044) were more common in non-survivors. Microbiological eradication and clinical response within 7 days were two major determinants of 28-day attributable mortality (p=0.001 and p=0.001, adjusted r(2)=0.845). Colistin-based dual combinations, and preferably triple combinations, were associated with significantly better outcomes when compared to non-colistin-based regimens (p<0.001). Time to active treatment had a significant effect on the course of infection (p=0.014).. Earlier active treatment with colistin based regimens and microbiological and clinical response within 7 days are major predictors of survival in cases of BSIs due to CRE. Rectal screening offers the advantage of earlier recognition and prompt empirical treatment.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Carbapenems; Case-Control Studies; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Female; Hospital Mortality; Humans; Klebsiella pneumoniae; Male; Middle Aged; Retrospective Studies; Risk Factors; Treatment Outcome

Nosocomial infections and their rational antibiotic treatment represent a major challenge for the healthcare nowadays. In this context, gramnegative bacteria including Pseudomonas aeruginosa, Acinetobacter baumanii and Enterobacteriaceae spp. are etiologically important and characterized by a significant level of antibiotic resistance. To examine dynamics of the respiratory tract colonization by hospital flora, tracheal aspirates obtained at three time points from 69 children with severe craniocerebral trauma during their stay in ICU were analysed. Colonization was observed on the 4th day of the ICU stay with predomination of K. pneumoniae (45%) and A. baumanii (27-37%). P. aeruginosa was detected after the 8th day of the ICU stay with the isolation rate of 33%. Substantial proportions of P. aeruginosa (61%), A. baumanii (78%) and K. pneumoniae (25%) were resistant to carbapenems. In 65 carbapemen resistant isolates, the presence of carbapenemases was examined using PCRs. OXA-48 carbapenemase was detected in 11 out of 14 (78%) K. pneumoniae isolates. Among the A. baumanii isolates, 30/31 (97%) carried OXA-40 and 1/31 (3%) had OXA-23 carbapenemases. None of the examined A. baumanii and K. pneumoniae isolates produced metallo-betalactamases (MBL). In contrast, all 20 carbapenem resistant P. aeruginosa isolates produced a MBL, and in 12 out of 20 (60%) of theme VIM-2 was detected. Thus, gramnegative nosocomial microflora rapidly colonizes ICU patients and has a high level of resistance to antibiotics, including carbapenems.

Topics: Acinetobacter baumannii; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; beta-Lactams; Child; Colistin; Craniocerebral Trauma; Cross Infection; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Gene Expression; Humans; Intensive Care Units, Pediatric; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Respiratory Tract Infections; Trachea; Trauma Severity Indices

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Gastrointestinal Tract; Humans; Male

Limited antimicrobials remain active for treating severe infections due to KPC-producing pathogens, and optimal regimens have not been established. In murine thigh infections caused by nine KPC-producing clinical strains of Enterobacteriaceae (meropenem MICs, 1 to 4 μg/ml), we evaluated the activities of tigecycline, colistin, meropenem, rifampin, and gentamicin in single and combination regimens lasting for 24 h and 48 h. Rifampin, tigecycline, and gentamicin were the most effective monotherapies, reducing significantly the CFU counts yielded from thighs infected by 88.9 to 100%, 77.8 to 88.9%, and 66.7 to 88.9% of strains, respectively; meropenem and colistin alone exhibited considerably lower performance (significant CFU reduction in 33.3% and 22.2 to 33.3% of the strains, respectively). The addition of rifampin or gentamicin to tigecycline produced synergistic effect in most strains, while antagonism was observed in 33.3 to 44.4% of the strains when colistin was added to tigecycline and in 44.4 to 55.5% of the strains for meropenem combination with tigecycline. Tigecycline combinations with gentamicin or with rifampin caused higher CFU reductions than did tigecycline plus colistin or plus meropenem with almost all strains. Furthermore, tigecycline plus gentamicin was significantly more effective than tigecycline plus colistin or tigecycline plus meropenem in 33.3 to 44.4% and 55.5 to 66.7% of the strains, respectively, while tigecycline plus rifampin significantly outperformed tigecycline plus colistin and tigecycline plus meropenem in 33.3% and 66.7 to 77.8% of the strains, respectively. Overall, our in vivo study showed that tigecycline plus rifampin or plus gentamicin is a robust regimen against soft tissue infections caused by KPC-producing strains. The combinations of tigecycline with colistin or meropenem should be considered with caution in clinical practice.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Colony Count, Microbial; Drug Synergism; Drug Therapy, Combination; Enterobacteriaceae Infections; Escherichia coli; Female; Gentamicins; Klebsiella pneumoniae; Meropenem; Mice; Microbial Sensitivity Tests; Minocycline; Rifampin; Thienamycins; Thigh; Tigecycline

This study was conducted in response to the rising incidence of drug resistance observed in the intensive care unit (ICU) of King Fahad Medical City.. A retrospective observational study was conducted in the ICU of King Fahad Medical City between October 2003 and April 2012. Data were collected using a structured data sheet.. Nine episodes of infection with colistin-resistant Enterobacteriacae were recorded in seven patients. Five were females with an average age of 59.75 years. All patients had multiple co-morbidities; five had diabetes mellitus. In five of the episodes, Klebsiella pneumoniae was responsible, Serratia marcescens was reported in two, while Enterobacter aerogenes and Providencia stuartii were responsible for one episode of infection each. Prior colistin use was documented in all but one patient. Colistin resistance was defined by a minimum inhibitory concentration (MIC) of > 4 µg/mL according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoint for Enterobacteriacae. Various antibiotics were used to treat the patients, with mortality reported in two.. Infection due to colistin-resistant Enterobacteriacae is a rising challenge in Saudi Arabia; colistin use is thought to be associated with these infections. This calls for a stricter antimicrobial stewardship program and improved infection control measures to curb the rising trend of antibiotic resistance.

Topics: Aged; Anti-Bacterial Agents; Colistin; Critical Illness; Cross-Sectional Studies; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Saudi Arabia

This study reports on the emergence of OXA-48-like carbapenemases among isolates of Enterobacteriaceae in South Africa. In addition, the emergence during therapy of a colistin-resistant OXA-181-producing Klebsiella pneumoniae isolate was documented following selective digestive tract decontamination with oral colistin, which is therefore strongly discouraged.

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Gastrointestinal Tract; Humans; Male; Middle Aged; South Africa

The New Delhi metallo-β-lactamase gene (bla(NDM-1)) has emerged as a worldwide concern among isolates of Enterobacteriaceae. Its epidemiology is been strongly associated with travel and healthcare on the Indian Subcontinent. We report two cases of urinary tract infection with Enterobacteriaceae harboring a bla(NDM-1). Both cases presented as infection in community-dwelling individuals in Australia and were associated with travel to the Indian Subcontinent. One isolate of Escherichia coli harbored the previously undescribed enzyme variant bla(NDM-3), differing from bla(NDM-1) by a single nonsynonymous SNP conferring a putative peptide sequence change at the 95th position (ASP→ASN). The second was an Enterobacter cloacae harboring bla(NDM-1). Further genetic characterization included identification of additional β-lactamase and aminoglycoside resistance genes. Legacy antimicrobials were used for treatment. Oral therapy with nitrofurantoin was successful in one case, while combination of colistin and rifampicin was required in the second patient. Such infection, due to extensively drug-resistant pathogens, poses significant challenges in balancing the efficacy and toxicity of potential antimicrobial therapies.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Escherichia coli; Female; Humans; Male; Nitrofurantoin; Polymorphism, Single Nucleotide; Rifampin; Urinary Tract Infections

New Delhi metallo-β-lactamase-1 (NDM-1)-producing Enterobacteriaceae have emerged as a global threat. The aim of this study was to assess the efficacies of colistin and tigecycline in an experimental model of pneumonia caused by NDM-1-producing Escherichia coli and Klebsiella pneumoniae. The susceptibilities of K. pneumoniae NDM, E. coli NDM and K. pneumoniae ATCC 29665 were determined using the broth microdilution technique. The pharmacokinetics of colistin and tigecycline in an experimental model of pneumonia were performed using immunocompetent C57BL/6 mice. Mice were treated with colistin (60 mg/kg/day) or tigecycline (10 mg/kg/day). Mortality, bacteraemia and lung bacterial concentrations were recorded. The strains were susceptible to colistin and tigecycline. The ratio of area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) for colistin was 158.5 (all three strains) and that for tigecycline was 18.5 (K. pneumoniae NDM) and 37 (K. pneumoniae ATCC 29665 and E. coli NDM). In vivo, colistin decreased bacterial lung concentrations of K. pneumoniae NDM and K. pneumoniae ATCC 29665 by 1.16 log colony-forming units (CFU)/g and 2.23 logCFU/g, respectively, compared with controls (not significant). Tigecycline reduced K. pneumoniae NDM and K. pneumoniae ATCC 29665 load by 2.67 logCFU/g and 4.62 logCFU/g (P<0.05). Colistin and tigecycline decreased lung concentrations of E. coli NDM by 2.27 logCFU/g and 4.15 logCFU/g (P<0.05), respectively, compared with controls, and was more active than colistin (P<0.05). In conclusion, these results suggest that colistin is inappropriate for treating pneumonia due to NDM-1-producing K. pneumoniae and its efficacy was suboptimal against NDM-1-producing E. coli. A high tigecycline dose was efficacious for treating experimental pneumonia due to NDM-1-producing E. coli and K. pneumoniae.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Load; Bacterial Proteins; beta-Lactamases; Colistin; Disease Models, Animal; Drug Evaluation, Preclinical; Enterobacteriaceae Infections; Escherichia coli; Female; Klebsiella pneumoniae; Lung; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Minocycline; Tigecycline

To describe the treatment and outcomes of patients with carbapenemase-producing Enterobacteriaceae and evaluate whether these cases represented active infection requiring antibiotic therapy or colonization.. Adult inpatients with carbapenemase-producing Enterobacteriaceae were retrospectively evaluated. Cases were classified as colonization versus infection by 2 infectious diseases physicians. Multiple cultures that grew in the same patient within a 2-week period were evaluated as a single case.. A total of 42 cases among 35 patients were identified. The mean age of the cohort was 67.7 ± 13.7 y, mean APACHE II score was 17.9 ± 8.6, and 77% of patients were in the intensive care unit when the carbapenem-producing Enterobacteriaceae was isolated. Klebsiella pneumoniae (84%) was the predominant organism; urine (36%), tissue/wound/drainage (25%), and blood (20%) were the most common sites of collection. Though 43% of cases were classified as colonization, 56% of these cases were treated with antibiotics. Only 1 patient characterized as colonized subsequently developed infection, 29 days later. Among infected cases, colistin (55%), meropenem (41%), aminoglycosides (32%), and tigecycline (27%) were used for treatment, and combination antimicrobial therapy was common (55%). Clinical and microbiological success was higher in patients receiving combination therapy (83% vs 60%, p = 0.35). Colistin monotherapy was only successful in urinary infections. All-cause hospital mortality was 29%.. Nearly half of cases represented colonization, yet the majority were treated with broad-spectrum antibiotics. Determining infection versus colonization is a critical first step in managing patients with carbapenemase-producing Enterobacteriaceae. The risk of not treating apparent colonization appears low.

Topics: Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Thienamycins; Treatment Outcome

Therapeutic options are limited for infections because of Acinetobacter baumannii and carbapenem-resistant Enterobacteriaceae (CRE). Study aim was to compare the efficacy of colistin to tigecycline for the treatment of these types of infections.. A retrospective study was conducted at the Detroit Medical Center. Adult patients with infections because of A baumannii or CRE in 2009 who received ≥2 doses of colistin or tigecycline were studied. Risk factors, outcomes, and costs were analyzed.. There were 82 patients with infections because of A baumannii, 12 with CRE, and 12 with A baumannii and CRE coinfection. Seventy-one patients received colistin, 16 received tigecycline, and 19 received both colistin and tigecycline. Seven isolates were nonsusceptible to colistin and 79 to tigecycline. Patients receiving colistin alone or in combination were more likely to die during their hospitalization than patients receiving only tigecycline (P = .002). However, patients receiving colistin had higher severity of acute illness and had notable delays in initiation of effective antimicrobial therapy (P < .001).. Compared with patients who received tigecycline alone, patients who received colistin alone or in combination had a higher severity of acute illness indices and delays in initiation of effective therapy. This increased severity of illness contributed to the increased rate of mortality among patients treated with colistin for A baumannii or CRE infections.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Case-Control Studies; Cohort Studies; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Male; Michigan; Middle Aged; Minocycline; Retrospective Studies; Severity of Illness Index; Survival Analysis; Tigecycline; Treatment Outcome

The authors had for aim to monitor Enterobacteriaceae resistance to colistin, during 6 years (2005-2010), and to study the epidemiology of Enterobacteriaceae resistant strains isolated in the Sfax region (Tunisia).. This retrospective study was carried out in the microbiology laboratory, at the Habib Bourguiba teaching hospital in Sfax. All strains of colistin resistant Enterobacteriaceae isolated from patients were studied.. One hundred and twenty one strains of colistin resistant Enterobacteriaceae were isolated from 93 patients. Klebsiella pneumoniae was the most frequent species (60.2%), followed by Enterobacter cloacae (26.9%), and Escherichia coli (12.9%). Thirteen strains (E. cloacae) were heteroresistant to colistin. Eighty one isolates (87.1%) were resistant to third generation cephalosporins. The rate of resistance to colistin ranged from 0.09% for E. coli to 1.2% for K. pneumoniae, and 1.5% for E. cloacae. A progressively increasing colistin resistance was observed for K. pneumoniae. Most resistant strains were isolated from urine in the urology department. Previous exposure to colistin was reported in 59.2% of patients. Pulsed field gel electrophoresis typing revealed different clones.. Colistin resistance in Enterobacteriaceae is a worrying phenomenon in Sfax. It is related to polyclonal diffusion. Continuous epidemiological monitoring and a rational use of colistin are necessary to limit the spreading of these colistin resistant strains and to maintain this antibiotic's effectiveness.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Child; Child, Preschool; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Retrospective Studies; Tunisia; Young Adult

From 2005 to 2009, at Detroit Medical Center, the prevalence of Providencia stuartii increased from 0.52 to 0.91/1000 patient-days (p<0.001). The use of colistin also increased (p<0.001) during the study period. The increase in the prevalence of P. stuartii was associated with an increased use of colistin (p<0.001). Facilities that frequently use colistin and tigecycline should closely monitor the prevalence of P. stuartii along with other Proteeae, since these organisms are intrinsically resistant to colistin and tigecycline.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae Infections; Female; Humans; Logistic Models; Michigan; Middle Aged; Minocycline; Prevalence; Providencia; Retrospective Studies; Tertiary Care Centers; Tigecycline

Colonisation and infection with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) is an emerging problem. The aim of this study was to investigate whether colistin, which is reported to be effective against multiresistant enterobacteria, prevents ESBL-E colonisation in neonates. For prophylaxis of necrotising enterocolitis, oral gentamicin (15 mg/kg/day) is routinely used in all neonates hospitalised at the Neonatal Intensive Care Unit of University Hospital Graz (Austria). During the study period from May 2005 to September 2007, three ESBL-E outbreaks (total duration 18 months) occurred. During these outbreaks, gentamicin was immediately replaced by oral colistin (8 mg/kg/day) in all hospitalised neonates. All neonates colonised with ESBL-E during the study period were retrospectively analysed with regard to the influence of colistin on ESBL-E colonisation. Genetic relatedness of isolates was assessed by repetitive sequence-based polymerase chain reaction (rep-PCR). During the study period, 30 (4.5%) of 667 neonates were colonised with ESBL-E. Twelve of twenty-one patients colonised with Klebsiella pneumoniae (ESBL-Kp) and one of nine patients colonised with Klebsiella oxytoca (ESBL-Ko) had received oral colistin at time of colonisation with ESBL-E. Amongst ESBL-Kp, the rate of colistin resistance was significantly higher in the colistin group (P=0.0075). Four different clones of ESBL-Kp and three different clones of ESBL-Ko were isolated, indicating the occurrence of patient-to-patient transmission. Colistin-resistant as well as colistin-susceptible isolates were detected within the same clones, indicating induction of resistance. At the dosage used, oral colistin did not prevent colonisation with ESBL-E and appeared to select colistin-resistant strains or to induce colistin resistance.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Austria; Bacterial Typing Techniques; beta-Lactamases; Carrier State; Cluster Analysis; Colistin; Disease Outbreaks; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Gastrointestinal Tract; Genotype; Hospitals; Humans; Infant, Newborn; Male; Molecular Typing; Retrospective Studies; Selection, Genetic

Antibiotic combinations including tigecycline have not been studied against Klebsiella pneumoniae carbapenemase (KPC)-producing pathogens. Tigecycline alone and combined with colistin and meropenem was tested against eight genetically unrelated KPC-producing clinical strains of Enterobacteriaceae (four K. pneumoniae, two Escherichia coli, one Enterobacter cloacae and one Serratia marcescens) by time-kill assay. Tigecycline displayed a concentration-independent bacteriostatic activity in seven strains and bactericidal activity in one strain. Colistin showed bactericidal activity at 4× the minimum inhibitory concentration (MIC) in three strains and was bacteriostatic for the remaining strains and concentrations. Meropenem was bactericidal in three strains and bacteriostatic in five strains. The tigecycline+meropenem combination was not bactericidal against the four K. pneumoniae strains and was non-synergistic against all eight strains. Tigecycline+colistin was bactericidal against all strains at most time intervals and concentrations and was also synergistic at 1× and 2× MIC against most strains up to 4-8h and at 4× MIC up to 24 h against all strains. These findings suggest that, at most drug concentrations, tigecycline, colistin and meropenem as single agents do not exhibit efficient bactericidal activity against most of the KPC-producing strains. Tigecycline alone might be a therapeutic option for infections caused by KPC-producers when bacteriostatic activity is adequate or combined with colistin when bactericidal activity is necessary. Additional in vivo tests are warranted to assess better the killing kinetics of tigecycline combinations against KPC-producers.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Colistin; Drug Combinations; Drug Resistance, Bacterial; Enterobacter cloacae; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Humans; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Minocycline; Serratia marcescens; Thienamycins; Tigecycline

Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly emerging in hospitals in the United States and are posing a significant threat. To better understand the transmission dynamics and the acquisition of resistant strains, a thorough analysis of epidemiologic and molecular characteristics was performed.. CRE isolated at Detroit Medical Center were analyzed from September 2008 to September 2009. bla(KPC) genes were investigated by polymerase chain reaction (PCR), and repetitive extragenic palindromic PCR (rep-PCR) was used to determine genetic similarity among strains. Epidemiologic and outcomes analyses were performed.. Ninety-two unique patient CRE isolates were recovered. Sixty-eight strains (74%) were Klebsiella pneumoniae, 7 were Klebsiella oxytoca, 15 were Enterobacter species, and 2 were Escherichia coli. Fifteen isolates (16%) were resistant to colistin, 14 (16%) were resistant to tigecycline, and 2 were resistant to all antimicrobials tested. The mean ± standard deviation age of patients was 63 ± 2 years. Sixty patients (68%) were admitted to the hospital from long-term care facilities. Only 70% of patients received effective antimicrobial therapy when infection was suspected, with a mean time to appropriate therapy of 120 ± 23 hours following sample culturing. The mean length of hospitalization after sample culturing was 18.6 ± 2.5 days. Of 57 inpatients, 18 (32%) died in the hospital. Independent predictors for mortality were intensive care unit stay (odds ratio [OR], 15.8; P = .003) and co-colonization with CRE and either Acinetobacter baumannii or Pseudomonas aeruginosa (OR, 17.2; P = .006). Among K. pneumoniae CRE, rep-PCR revealed 2 genetically related strains that comprised 70% and 20% of isolates, respectively.. In this large U.S. cohort of patients with CRE infection, which reflects the modern continuum of medical care, co-colonization with CRE and A. baumannii or P. aeruginosa was associated with increased mortality. Two predominant clones of K. pneumoniae accounted for the majority of cases of CRE infection.

Topics: Academic Medical Centers; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Child; Child, Preschool; Colistin; Disease Reservoirs; Drug Resistance, Multiple, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Genotype; Hospital Mortality; Humans; Infant; Length of Stay; Male; Michigan; Middle Aged; Minocycline; Nursing Homes; Retrospective Studies; Tigecycline; Treatment Outcome; Young Adult

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Microbial Sensitivity Tests

There has been an increase in recent years of antimicrobial resistance of Gram negative bacilli (GNB). Carbapenems, the mainstay for the treatment of multidrug resistant GNB infections, are no longer always effective leaving treatment options limited. We present the case of patient with recurrent, complicated urinary tract infections. The current episode was caused by carbapenem-resistant K. pneumoniae and P. aeruginosa and carbapenem-susceptible, but MDR E. cloacae. Resistance to carbapenems of K. pneumoniae was conferred by the production of the class B metallo-beta-lactamase, VIM1. Infection control measures were implemented and following a 2-week course of treatment with colistin, the infection resolved and the patient was discharged. We discuss the changes in the epidemiology, the mechanisms involved and the means of detecting carbapenem resistance in GNB. We would also like to stress the role of infection control measures in limiting patient-to-patient spread of MDR organisms which, are of paramount importance in cases when few treatment options are left available.

Topics: Aged; Anastomosis, Surgical; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Infection Control; Klebsiella Infections; Klebsiella pneumoniae; Male; Nephrolithiasis; Pseudomonas aeruginosa; Pseudomonas Infections; Risk Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms; Urinary Tract Infections

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae Infections; Hafnia alvei; Humans; Microbial Sensitivity Tests

Increasing antibiotic resistance in gram-negative bacteria has recently renewed interest in colistin as a therapeutic option. The increasing use of colistin necessitates the availability of rapid and reliable methods for colistin susceptibility testing. We compared seven methods of colistin susceptibility testing (disk diffusion, agar dilution on Mueller-Hinton [MH] and Isosensitest agar, Etest on MH and Isosensitest agar, broth microdilution, and VITEK 2) on 102 clinical isolates collected from patient materials during a selective digestive decontamination or selective oral decontamination trial in an intensive-care unit. Disk diffusion is an unreliable method to measure susceptibility to colistin. High error rates and low levels of reproducibility were observed in the disk diffusion test. The colistin Etest, agar dilution, and the VITEK 2 showed a high level of agreement with the broth microdilution reference method. Heteroresistance for colistin was observed in six Enterobacter cloacae isolates and in one Acinetobacter baumannii isolate. This is the first report of heteroresistance to colistin in E. cloacae isolates. Resistance to colistin in these isolates seemed to be induced upon exposure to colistin rather than being caused by stable mutations. Heteroresistant isolates could be detected in the broth microdilution, agar dilution, Etest, or disk diffusion test. The VITEK 2 displayed low sensitivity in the detection of heteroresistant subpopulations of E. cloacae. The VITEK 2 colistin susceptibility test can therefore be considered to be a reliable tool to determine susceptibility to colistin in isolates of genera that are known not to exhibit resistant subpopulations. In isolates of genera known to (occasionally) exhibit heteroresistance, an alternative susceptibility testing method capable of detecting heteroresistance should be used.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Agar; Anti-Bacterial Agents; Bacterial Infections; Colistin; Cross Infection; Culture Media; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Intensive Care Units; Microbial Sensitivity Tests; Polymyxin B

Enterobacter aerogenes is an agent of hospital-acquired infection that exhibits a remarkable resistance to beta-lactam antibiotics during therapy. Five successive isolates of E. aerogenes infecting a patient and exhibiting a multiresistance phenotype to beta-lactam antibiotics and fluoroquinolones were investigated. Among these clinical strains, four presented resistant phenotypes during successive imipenem and colistin treatments. The involved resistance mechanisms exhibited by the successive isolates were associated with alterations of the outer membrane that caused a porin decrease and lipopolysaccharide modifications.

Topics: Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Enterobacter aerogenes; Enterobacteriaceae Infections; Evolution, Molecular; Female; Humans; Imipenem; Microbial Sensitivity Tests; Middle Aged; Porins

A comparison was made of different culture media and procedures for detection of Serratia marcescens from faecal, pharyngeal and ocular swabs collected from 213 neonates. MacConkey agar and MacConkey agar with sorbitol (1%) and/or colistin (200 i.u./ml) were used both for primary isolation and after enrichment using Mossel Enterobacteriaceae broth with colistin (200 i.u./ml). The use of MacConkey agar supplemented with colistin for primary isolation improved considerably the isolation rate of S. marcescens from faecal swabs but not from pharyngeal swabs; the number of ocular isolations were insufficient to demonstrate differences between procedures. Moreover the enrichment procedures consistently increased the number of S. marcescens isolates especially from pharyngeal and ocular swabs. Use of sorbitol made detection of S. marcescens from clinical specimens easier and time- and cost-efficient.

Topics: Colistin; Culture Media; Enterobacteriaceae Infections; Eye; Feces; Humans; Infant, Newborn; Pharynx; Serratia marcescens; Sorbitol

Topics: Anti-Bacterial Agents; Colistin; Enterobacteriaceae Infections; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestines; Klebsiella; Sepsis; Serotyping

Edwardsiella tarda is an uncommon enteric bacterium which has been found generally in animal hosts and occasionally in human feces. Three cases of extraintestinal infection caused by E. tarda which are described herein include a typhoid-like illness, peritonitis with sepsis, and cellulitis from a wound acquired while fishing. The microbiology of E. tarda and the previous reports of infection due to this organism are reviewed.

Topics: Adult; Cellulitis; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Male; Middle Aged; Peritonitis

Topics: Anti-Bacterial Agents; Colistin; Colon; Drug Resistance, Microbial; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Intestinal Diseases; Kanamycin; Postoperative Complications; Preoperative Care; Rectum

An epidemic caused by Serratia marcescens occurred in intensive care unit of the Children's clinic in Essen, with three deaths. Although there was good sensitivity of the strain to gentamicin in vitro, there was no noticeable clinical improvement when it was administered. But cotrimoxazole, given systemically and locally, and colistin locally cured the disease.

Topics: Colistin; Cross Infection; Disease Outbreaks; Enterobacteriaceae Infections; Gentamicins; Germany, West; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Intensive Care Units; Sepsis; Serratia marcescens; Sulfamethoxazole; Trimethoprim

Topics: Ampicillin; Bacitracin; Bacterial Infections; Carbenicillin; Cephalexin; Cephaloridine; Chloramphenicol; Colistin; Dexamethasone; Dicloxacillin; Enterobacteriaceae; Enterobacteriaceae Infections; Gentamicins; Humans; Microbial Sensitivity Tests; Neomycin; Penicillin G; Penicillin Resistance; Root Canal Therapy; Streptococcal Infections; Streptococcus; Tetracycline; Tooth Diseases

Topics: Ampicillin; Anti-Bacterial Agents; Carbenicillin; Chloramphenicol; Colistin; Drug Combinations; Drug Interactions; Drug Synergism; Enterobacteriaceae Infections; Erythromycin; Gentamicins; Glycosides; Humans; Hydrogen-Ion Concentration; Infections; Neoplasms; Novobiocin; Penicillins; Polymyxins; Streptomycin; Sulfonamides; Tetracycline; Trimethoprim

Topics: Algeria; Ampicillin; Anti-Bacterial Agents; Cephalosporins; Chloramphenicol; Colistin; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Furazolidone; Gentamicins; Humans; Kanamycin; Klebsiella; Penicillin Resistance; Proteus; Salmonella; Salmonella typhi; Streptomycin; Tetracycline

Topics: Aged; Bacteriological Techniques; Colistin; Enterobacteriaceae Infections; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Middle Aged; Pseudomonas Infections; Urinary Tract Infections

Topics: Colistin; Enterobacteriaceae Infections; Escherichia coli Infections; Humans; Klebsiella Infections; Polymyxins; Pseudomonas Infections

Topics: Ampicillin; Chloramphenicol; Colistin; Cross Infection; Enterobacter; Enterobacteriaceae; Enterobacteriaceae Infections; Epidemiologic Methods; Escherichia coli; Housekeeping, Hospital; Humans; Kanamycin; Methods; Otorhinolaryngologic Diseases; Proteus; Proteus Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Tetracycline

Topics: Animals; Brain; Chloramphenicol; Colistin; Electrocardiography; Enterobacteriaceae; Enterobacteriaceae Infections; Female; Fever; Humans; Infant, Newborn; Infant, Newborn, Diseases; Leukocyte Count; Meningitis; Penicillins; Sepsis; Snakes; Spinal Puncture; Streptomycin; Sulfadiazine

Topics: Adult; Cephalothin; Child; Colistin; Cross Infection; Enterobacter; Enterobacteriaceae Infections; Gentamicins; Germany, West; Humans; Infant, Newborn; Middle Aged; Penicillin Resistance; Penicillins; Postoperative Complications; Sepsis

Topics: Colistin; Enterobacter aerogenes; Enterobacteriaceae Infections; Humans; Klebsiella; Paraplegia; Toxicology; Urinary Tract Infections