meropenem and Escherichia-coli-Infections

A 73-year-old woman was admitted with consciousness disturbance following a fever. Abdominal computed tomography revealed a large liver abscess with which the presence of Desulfovibrio desulfuricans and Escherichia coli was confirmed by thorough blood and abscess content culture. Empiric meropenem treatment was switched to cefoperazone/sulbactam, followed by ampicillin/sulbactam based on susceptibility testing. Desulfovibrio desulfuricans is a common bacterium that rarely causes liver abscess and may be overlooked during co-infection due to overgrowth of the accompanying bacteria. Clinicians should bear Desulfovibrio desulfuricans in mind and select the appropriate antibiotics according to susceptibility testing when anaerobic bacteria are detected in a liver abscess.

Topics: Aged; Ampicillin; Cefoperazone; Coinfection; Desulfovibrio desulfuricans; Desulfovibrionaceae Infections; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Humans; Liver Abscess; Meropenem; Thienamycins

Topics: Anti-Bacterial Agents; Biopsy; Colitis, Ischemic; Colonic Diseases; Colonoscopy; Colostomy; Combined Modality Therapy; Escherichia coli Infections; Gastrointestinal Hemorrhage; Humans; Intestinal Mucosa; Male; Meropenem; Mesentery; Middle Aged; Morphine; Panniculitis, Peritoneal; Parenteral Nutrition, Total; Prednisone; Pseudomonas Infections; Tamoxifen; Thienamycins; Travel

Community acquired bacterial meningitis due to extended spectrum β lactamase-producing Escherichia coli is very rare. We report the case of a 72-year-old woman being treated for longstanding diabetes mellitus. She developed lower back pain accompanied by elevated body temperature, and was transported to the emergency unit in our hospital five days later because of impaired consciousness. An abdominal plane CT showed acute pyelonephritis and a brain MRI showed inflammatory exudate in the posterior horn of her bilateral ventricles. A lumbar puncture was performed, and examination of the cerebrospinal fluid revealed a marked elevation in her cell count (polymorphonuclear leukocytes dominant) that we diagnosed as bacterial meningitis. Initially, she was treated with intravenous meropenem, ceftriaxon, and vancomycin. Extended spectrum β lactamase-producing Escherichia coli were then detected in her urinary and blood cultures, and the antibiotics were changed to intravenous meropenem, gentamicin, and intrathecal gentamicin. Her clinical symptoms improved, but her inflammatory reaction was prolonged and we detected spondylitis. She was then treated with levofloxacin, and the inflammatory reaction improved. Extended spectrum β lactamase-producing Escherichia coli should be taken into consideration as a cause of community acquired bacterial meningitis.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Community-Acquired Infections; Escherichia coli; Escherichia coli Infections; Female; Gentamicins; Humans; Infusions, Intravenous; Meningitis, Bacterial; Meropenem; Thienamycins; Treatment Outcome

Hemophagocytic lymphohistiocytosis (HLH) is a rare condition with high mortality. We report a case of a 74-year-old woman with rheumatoid arthritis who developed HLH secondary to pyelonephritis due to Escherichia coli infection following infliximab treatment. Bone marrow aspiration showed proliferation of histiocytes with hemophagocytosis. The patient died despite treatment with intravenous antibiotics intravenous methylprednisolone and intravenous immunoglobulin. Cytokine levels were measured and are discussed.

Topics: Aged; Anti-Bacterial Agents; Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Rheumatoid; Bone Marrow; Escherichia coli Infections; Fatal Outcome; Female; Histiocytes; Humans; Immunocompromised Host; Immunoglobulins, Intravenous; Immunosuppressive Agents; Infliximab; Lymphohistiocytosis, Hemophagocytic; Meropenem; Methylprednisolone; Pyelonephritis; Thienamycins

Topics: Acute Disease; Amikacin; Anemia, Aplastic; Antilymphocyte Serum; Combined Modality Therapy; Cyclosporine; Drug Therapy, Combination; Escherichia coli Infections; Gastric Mucosa; Gastritis; Granulocyte Colony-Stimulating Factor; Immunosuppressive Agents; Meropenem; Methylprednisolone; Necrosis; Neutropenia; Omeprazole; Parenteral Nutrition, Total; T-Lymphocytes; Thienamycins

Multidrug resistant (MDR)

Topics: Animals; Anti-Bacterial Agents; Cattle; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Male; Meropenem; Microbial Sensitivity Tests; Trimethoprim, Sulfamethoxazole Drug Combination

Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum β-lactamase producers.. To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae.. Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study.. Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician.. The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used.. Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group.. Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting.. anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Cause of Death; Ceftriaxone; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Thienamycins

The increase in infections caused by drug-resistant ESBL-producing Enterobacteriaceae (ESBL-ENT) is a global concern. The characteristics and outcomes of patients infected with ESBL-ENT were examined in a pooled analysis of Phase 3 clinical trials of ceftolozane/tazobactam in patients with complicated urinary tract infections (ASPECT-cUTI) and complicated intra-abdominal infections (ASPECT-cIAI).. Trials were randomized and double blind. The ASPECT-cUTI regimen was 7 days of either intravenous ceftolozane/tazobactam (1.5 g) every 8 h or levofloxacin (750 mg) once daily. The ASPECT-cIAI regimen was 4-14 days of either intravenous ceftolozane/tazobactam (1.5 g) plus metronidazole (500 mg) or meropenem (1 g) every 8 h. Baseline cultures were obtained in both indications. Enterobacteriaceae were selected for ESBL characterization based on predefined criteria and were verified genotypically. Outcomes were assessed at the test-of-cure visit 5-9 days post-therapy in ASPECT-cUTI and 24-32 days post-randomization in ASPECT-cIAI among microbiologically evaluable (ME) patients.. Of 2076 patients randomized, 1346 were included in the pooled ME population and 150 of 1346 (11.1%) had ESBL-ENT at baseline. At US FDA/EUCAST breakpoints of ≤2/≤1 mg/L, 81.8%/72.3% of ESBL-ENT (ESBL-Escherichia coli, 95%/88.1%; ESBL-Klebsiella pneumoniae, 56.7%/36.7%) were susceptible to ceftolozane/tazobactam versus 25.3%/24.1% susceptible to levofloxacin and 98.3%/98.3% susceptible to meropenem at CLSI/EUCAST breakpoints. Clinical cure rates for ME patients with ESBL-ENT were 97.4% (76/78) for ceftolozane/tazobactam [ESBL-E. coli, 98.0% (49 of 50); ESBL-K. pneumoniae, 94.4% (17 of 18)], 82.6% (38 of 46) for levofloxacin and 88.5% (23 of 26) for meropenem.. Randomized trial data demonstrated high clinical cure rates with ceftolozane/tazobactam treatment of cIAI and cUTI caused by ESBL-ENT.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents, Urinary; beta-Lactamase Inhibitors; beta-Lactamases; Cephalosporins; Double-Blind Method; Escherichia coli; Escherichia coli Infections; Female; Genotype; Humans; Intraabdominal Infections; Klebsiella Infections; Klebsiella pneumoniae; Levofloxacin; Male; Meropenem; Metronidazole; Middle Aged; Penicillanic Acid; Tazobactam; Thienamycins; Treatment Outcome; Urinary Tract Infections; Young Adult

To evaluate the efficacy of meropenem single dose before transrectal prostate biopsy, instead of ciprofloxacin in the era of fluoroquinolones resistance.. This prospective study included patients with indications for prostatic biopsy from January to December 2014. Those with known resistance in fluoroquinolones or meropenem or with decreased creatinine clearance were excluded. Patients were randomized into two groups, and statistical analysis was carried out. Group A received a 3-day course of ciprofloxacin 500 bid per os starting the day before biopsy. Group B received 1 g meropenem intravenously 1 h prior to the procedure. Patients were followed up for 15 days, and those with lower urinary tract symptoms (LUTS) and fever were called for hospitalization. Urine and blood cultures were obtained.. A total of 110 patients, 52-75 years old (mean 67.5, median 66) participated in the study, allocated in Groups A and B. After the procedure, 18 patients (32.7 %) of Group A reported macroscopic hematuria, while 10 (18.2 %) reported rectal blood loss. Nine patients (16.3 %) presented because of fever and LUTS. One of them developed septic shock and died in the ICU. Cultures revealed multi-resistant E. coli with high sensitivity to meropenem, and patients were treated accordingly. In Group B, 20 (36.3 %) patients presented with macroscopic hematuria and 9 (16.3 %) with rectal blood loss. One patient returned to hospital with LUTS and fever. Cultures revealed Klebsiella pneumoniae sensitive to colimycine.. A single dose of meropenem prior to prostate biopsy is a safe and effective way to avoid the possible infectious complications in high-risk patients.

Topics: Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Biopsy, Needle; Ciprofloxacin; Dose-Response Relationship, Drug; Endosonography; Escherichia coli; Escherichia coli Infections; Follow-Up Studies; Humans; Image-Guided Biopsy; Male; Meropenem; Middle Aged; Prospective Studies; Prostatic Diseases; Rectum; Thienamycins; Time Factors

Gram-negative bacteria such as Escherichia coli or Klebsiella spp. frequently cause bloodstream infections. There has been a worldwide increase in resistance in these species to antibiotics such as third generation cephalosporins, largely driven by the acquisition of extended-spectrum beta-lactamase or plasmid-mediated AmpC enzymes. Carbapenems have been considered the most effective therapy for serious infections caused by such resistant bacteria; however, increased use creates selection pressure for carbapenem resistance, an emerging threat arising predominantly from the dissemination of genes encoding carbapenemases. Recent retrospective data suggest that beta-lactam/beta-lactamase inhibitor combinations, such as piperacillin-tazobactam, may be non-inferior to carbapenems for the treatment of bloodstream infection caused by extended-spectrum beta-lactamase-producers, if susceptible in vitro. This study aims to test this hypothesis in an effort to define carbapenem-sparing alternatives for these infections.. The study will use a multicentre randomised controlled open-label non-inferiority trial design comparing two treatments, meropenem (standard arm) and piperacillin-tazobactam (carbapenem-sparing arm) in adult patients with bacteraemia caused by E. coli or Klebsiella spp. demonstrating non-susceptibility to third generation cephalosporins. Recruitment is planned to occur in sites across three countries (Australia, New Zealand and Singapore). A total sample size of 454 patients will be required to achieve 80% power to determine non-inferiority with a margin of 5%. Once randomised, definitive treatment will be for a minimum of 4 days, but up to 14 days with total duration determined by treating clinicians. Data describing demographic information, antibiotic use, co-morbid conditions, illness severity, source of infection and other risk factors will be collected. Vital signs, white cell count, use of vasopressors and days to bacteraemia clearance will be recorded up to day 7. The primary outcome measure will be mortality at 30 days, with secondary outcomes including days to clinical and microbiological resolution, microbiological failure or relapse, isolation of a multi-resistant organism or Clostridium difficile infection.. The MERINO trial is registered under the Australian New Zealand Clinical Trials Register (ANZCTR), reference number: ACTRN12613000532707 (registered 13 May 2013) and the US National Institute of Health ClinicalTrials.gov register, reference number: NCT02176122 (registered 24 June 2014).

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Clinical Protocols; Drug Resistance, Microbial; Escherichia coli Infections; Humans; Klebsiella Infections; Meropenem; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sample Size; Thienamycins

Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future.. The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a 'real practice' multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli.. Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals.. This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects with this drug, whether as monotherapy or combination therapy.. NCT02142751. EudraCT no: 2013-002922-21. Protocol V.1.1 dated 14 March 2014.

Topics: Administration, Intravenous; Anti-Bacterial Agents; beta-Lactamases; Clinical Protocols; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Gastrointestinal Microbiome; Gram-Negative Bacteria; Humans; Intestines; Meropenem; Research Design; Thienamycins; Urinary Tract Infections

Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM-7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions. The results are summarized as follows. 1. Pharmacokinetic studies. MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion. Peak plasma concentrations (Cmax's) and plasma half-lives (T1/2's) of these doses were 28.5, 47.2 and 130.0 micrograms/ml, and 0.80, 0.93 and 0.94 hours, respectively. A clear dose response was observed in Cmax's and T1/2 values were quite similar to those observed in adults. In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine. The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 microgram/ml at a dose of 6 mg/kg, and 0.64 to 4.22 micrograms/ml at a dose of 29 to 44 mg/kg within day 4 of onset. The penetration rate of MEPM showed an intermediate value among those for other cephalosporin antibiotics. 2. Clinical study. Clinical efficacies of MEPM were evaluated in 389 cases. The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day. The maximum dose was 173 mg/kg/day q.i.d. MEPM gave "excellent" or "good" responses in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified. Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI. Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment. Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains). The overall eradication rate for Gram-positive bacteria was 94.6%. Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated. The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated. Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave "excellent" or "good" responses in 77 cases (91.7%) and excellent bacteriological responses (95.7%).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Bacterial Infections; Child; Child, Preschool; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Moraxella catarrhalis; Neisseriaceae Infections; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Thienamycins

The authors report three trials of B-lactams and carbapenems for soft tissue infections treated on a surgical service: 1) cefmetazole versus cefoperazone, n = 44; 2) cefotetan versus cefoxitin, n = 24; and 3) meropenem versus imipenem, n = 44. A total of 138 hospitalized patients were enrolled with 112 meeting evaluability criteria. Four hundred twenty-three isolates were cultured (mean, three/patient) of which 67 per cent were aerobes and 33 per cent anaerobes. Cure rates for each trial were: 1) 93 per cent; 2) 92 per cent; 3) 100 per cent. Failures were caused by resistant organisms (Streptococcus group D, Bacteroides fragilis and Pseudomonas) appearing in incompletely drained infection sites. Three patients receiving meropenem had adverse effects (headache, nausea) and one receiving cefoxitin (truncal rash). Operative drainage and debridement remain the critical elements in therapy. Agents with longer half lives allowing twice daily dosing (cefmetazole and cefotetan) were as effective and less expensive than multiple doses of short-acting agents. The extended spectrum carbapenems are most useful for severe infections or resistant organisms.

Topics: Adult; Aged; Bacterial Infections; Carbapenems; Cefmetazole; Cefoperazone; Cefotetan; Cefoxitin; Cephalosporins; Drug Combinations; Drug Resistance, Microbial; Escherichia coli Infections; Female; Humans; Imipenem; Male; Meropenem; Middle Aged; Prospective Studies; Remission Induction; Skin Diseases, Infectious; Staphylococcal Infections; Streptococcal Infections; Thienamycins

Whole genome sequencing (WGS) enables detailed characterization of bacteria at single nucleotide resolution. It provides data about acquired resistance genes and mutations leading to resistance. Although WGS is becoming an essential tool to predict resistance patterns accurately, comparing genotype to phenotype with WGS is still in its infancy. Additional data and validation are needed. In this retrospective study, we analysed 234 E. coli isolates from positive blood cultures using WGS as well as microdilution for 11 clinically relevant antibiotics, to compare the two techniques. We performed whole genome sequencing analyses on 234 blood culture isolates (genotype) to detect acquired antibiotic resistance. Minimal inhibitory concentrations (MIC) for E. coli were performed for amoxicillin, cefepime, cefotaxime, ceftazidime, meropenem, amoxicillin/clavulanic acid, piperacillin/tazobactam, amikacin, gentamicin, tobramycin, and ciprofloxacin, using the ISO 20776-1 standard broth microdilution method as recommended by EUCAST (phenotype). We then compared the two methods for statistical 'agreement'. A perfect (100%) categorical agreement between genotype and phenotype was observed for gentamicin and meropenem. However, no resistance to meropenem was observed. A high categorical agreement (> 95%) was observed for amoxicillin, cefepime, cefotaxime, ceftazidime, amikacin, and tobramycin. A categorical agreement lower than 95% was observed for amoxicillin/clavulanic acid, piperacillin/tazobactam, and ciprofloxacin. Most discrepancies occurred in isolates with MICs within ± 1 doubling dilution of the breakpoint and 22.73% of the major errors were samples that tested phenotypically susceptible at higher antibiotic exposure and were therefore considered as 'not resistant'. This study shows that WGS can be used as a valuable tool to predict phenotypic resistance against most of the clinically relevant antibiotics used for the treatment of E. coli bloodstream infections.

Topics: Amikacin; Amoxicillin; Anti-Bacterial Agents; Cefepime; Cefotaxime; Ceftazidime; Ciprofloxacin; Clavulanic Acid; Escherichia coli; Escherichia coli Infections; Genotype; Gentamicins; Humans; Meropenem; Microbial Sensitivity Tests; Phenotype; Piperacillin; Retrospective Studies; Tazobactam; Tobramycin; Whole Genome Sequencing

Cefepime is a first-line agent for empiric sepsis therapy; however, cefepime use may be associated with increased mortality for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in an MIC-dependent manner. This study aimed to compare the efficacy of empiric cefepime versus meropenem for bloodstream infections (BSI) caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae with cefepime MICs ≤ 2 mg/L.. This single-center retrospective cohort study included patients admitted from October 2010 to August 2020 who received cefepime or meropenem empirically for sepsis with a blood culture growing ceftriaxone-resistant Escherichia coli or Klebsiella pneumoniae. The primary outcome was 30-day mortality; secondary endpoints included 14-day mortality, recurrent BSI, readmission and recurrent infection within 90 days, time to clinical resolution of infection, time to clinical stability, and clinical stability at 48 hours.. Fifty-four patients met inclusion criteria: 36 received meropenem and 18 received cefepime. The median (IQR) treatment durations of cefepime and meropenem were 3 (2-6) days and 7 (5-10) days, respectively. Thirty-day and 14-day mortality were similar between cefepime and meropenem (11.1% vs. 2.8%; P = 0.255 and 5.6% vs. 2.8%; P = 1.00, respectively). Cefepime was associated with longer time to clinical stability compared with meropenem (median 38.48 hours vs. 21.26; P = 0.016).. Mortality was similar between groups, although most patients who received cefepime empirically were ultimately transitioned to a carbapenem to complete the full treatment course. Empiric cefepime was associated with a delay in achieving clinical stability when compared with meropenem to treat BSI caused by ceftriaxone-resistant Enterobacterales, even when cefepime-susceptible.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Sepsis

Cefmetazole is active against extended-spectrum β-lactamase-producing

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefmetazole; Escherichia coli; Escherichia coli Infections; Humans; Meropenem; Urinary Tract Infections

Antibiotic persistence is a phenomenon observed when genetically susceptible cells survive long-term exposure to antibiotics. These 'persisters' are an intrinsic component of bacterial populations and stem from phenotypic heterogeneity. Persistence to antibiotics is a concern for public health globally, as it increases treatment duration and can contribute to treatment failure. Furthermore, there is a growing array of evidence that persistence is a 'stepping-stone' for the development of genetic antimicrobial resistance. Urinary tract infections (UTIs) are a major contributor to antibiotic consumption worldwide, and are known to be both persistent (i.e. affecting the host for a prolonged period) and recurring. Currently, in clinical settings, routine laboratory screening of pathogenic isolates does not determine the presence or the frequency of persister cells. Furthermore, the majority of research undertaken on antibiotic persistence has been done on lab-adapted bacterial strains. In the study presented here, we characterized antibiotic persisters in a panel of clinical uropathogenic

Topics: Anti-Bacterial Agents; Bacteria; Colistin; Escherichia coli Infections; Humans; Meropenem; Urinary Tract Infections; Uropathogenic Escherichia coli

Urosepsis caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. Carbapenems are commonly recommended for the treatment of ESBL infections; however, to minimize the emergence of carbapenem resistance, interest in alternative treatments has heightened.. This study compared pharmacodynamics of piperacillin/tazobactam versus meropenem against ESBL-producing and non-producing E. coli clinical isolates.. E. coli isolates, obtained from national reference laboratory in Bangladesh, were characterized by phenotypic tests, WGS, susceptibility tests and mutant frequency analysis. Three ESBL-producing and two non-producing E. coli were exposed to piperacillin/tazobactam (4.5 g, every 6 h and every 8 h, 30 min infusion) and meropenem (1 g, every 8 h, 30 min infusion) in a hollow-fibre infection model over 7 days.. Piperacillin/tazobactam regimens attained ∼4-5 log10 cfu/mL bacterial killing within 24 h and prevented resistance emergence over the experiment against ESBL-producing and non-producing E. coli. However, compared with 8 hourly meropenem, the 6 hourly piperacillin/tazobactam attained ∼1 log10 lower bacterial kill against one of three ESBL-producing E. coli (CTAP#173) but comparable killing for the other two ESBL-producing (CTAP#168 and CTAP#169) and two non-producing E. coli (CTAP#179 and CTAP#180). The 6 hourly piperacillin/tazobactam regimen attained ∼1 log10 greater bacterial kill compared with the 8 hourly regimen against CTAP#168 and CTAP#179 at 24 h.. Our study suggests piperacillin/tazobactam may be a potential alternative to carbapenems to treat urosepsis caused by ESBL-producing E. coli, although clinical trials with robust design are needed to confirm non-inferiority of outcome.

Topics: Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Escherichia coli; Escherichia coli Infections; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination

Topics: Agar; Ampicillin; Animals; Anti-Bacterial Agents; Biofilms; Drug Resistance, Bacterial; Ertapenem; Escherichia coli Infections; Female; Imipenem; Meropenem; Norfloxacin; Saudi Arabia; Sheep; Urinary Tract Infections; Uropathogenic Escherichia coli; Virulence Factors

Antibiotic combinations remain the frontline therapy for severe infections to reduce mortality. However, conventional antibiotic combinations have some limitations such as the low bioavailability and the rise of resistant strains. Nanoparticles are increasingly used as antibiotic delivery systems to promote bioavailability and hence improve efficacy of antibiotics. In this work, we hypothesize that the simultaneous delivery of two antibiotic-loaded nanoparticles will improve the intracellular bioavailability and thus inhibit emergence of resistance. Accordingly, Chitosan-pluronic nanoparticles were used to construct nanosized ciprofloxacin and meropenem and the antibacterial activity of nanosized combined antibiotics were compared versus unloaded single, unloaded combined, and nanosized single antibiotics. Thirty-six stepwise mutants were selected by exposing two

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Chitosan; Ciprofloxacin; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Meropenem; Microbial Sensitivity Tests; Multidrug Resistance-Associated Proteins; Poloxamer; Porins

Antimicrobial resistance (AMR) is a recognised threat to global health. Obtaining data on the prevalence of AMR in environmental bacteria is key to understanding drivers and routes of transmission. Here, 325 Shiga toxin negative deer faecal samples-gathered from across the Scottish mainland-were screened for the presence of AMR Escherichia coli and investigated for potential risk factors associated with AMR occurrence. E. coli with resistance to antimicrobials of clinical health concern, including carbapenems and 3rd generation cephalosporins, were targeted. Ninety-nine percent of samples yielded E. coli, and the prevalence of resistant E. coli at the level of faecal samples was 21.8% (n = 71) for tetracycline, 6.5% (n = 21) for cefpodoxime, 0.3% for ciprofloxacin (n = 1), with no recorded resistance to meropenem. Potential risk factors for tetracycline and cefpodoxime resistance were investigated. The presence of broadleaved woodlands was significantly associated with both AMR phenotypes, which may relate to land use within or around such woodlands. Associated risk factors varied across resistance phenotype and deer species, with proximity or density of horses an indicator of significantly decreased and increased risk, respectively, or tetracycline and cefpodoxime resistance in E. coli from roe deer, but not from red deer. Distance from wastewater treatment plants was a significant risk factor for tetracycline resistance in E. coli from red deer but not from roe deer. Data indicated that AMR E. coli can occur in wild deer populations that are not directly exposed to the selective pressure exerted by antimicrobial treatment. Overall, resistance to critically important antimicrobials was found to be low in the studied population, suggesting no immediate cause for concern regarding human health. Utilising existing culling frameworks, wild deer in Scotland could function well as a sentinel species for the surveillance of AMR in the Scottish environment.

Topics: Animals; Animals, Wild; Anti-Bacterial Agents; Anti-Infective Agents; Cefpodoxime; Ceftizoxime; Ciprofloxacin; Deer; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Horses; Humans; Meropenem; Prevalence; Risk Factors; Shiga Toxins; Tetracyclines

Antimicrobial resistance is associated with increased morbidity in secondary infections and is a global threat owning to the ubiquitous nature of resistance genes in the environment. Recent estimate put the deaths associated with bacterial antimicrobial resistance in 2019 at 4.95 million worldwide. Lymphatic filariasis (LF), a Neglected Tropical Disease (NTD), is associated with the poor living in the tropical regions of the world. LF patients are prone to developing acute dermatolymphangioadenitis (ADLA), a condition that puts them at risk of developing secondary bacterial infections due to skin peeling. ADLA particularly worsens the prognosis of patients leading to usage of antibiotics as a therapeutic intervention. This may result in inappropriate usage of antibiotics due to self-medication and non-compliance; exacerbating antimicrobial resistance in LF patients. In this perspective, we assessed the possibilities of antimicrobial resistance in LF patients. We focused on antibiotic usage, antibiotic resistance in Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa isolates and looked at genes (mecA and Extended-spectrum beta-lactamase [blaCTX-M, blaSHV and blaTEM]) coding for resistance in multi-drug resistant (MDR) bacterial isolates.. Of the sixty (60) participants, fifty-four (n = 54, 90%) were within 31-60 years of age, twenty (n = 20, 33.33%) were unemployed and thirty-eight (n = 38, 50.67%) had wounds aged (in months) seven (7) months and above. Amoxicillin (54%) and chloramphenicol (22%) were the most frequently used antibiotics for self-medication. Staphylococcus aureus isolates (n = 26) were mostly resistant to penicillin (n = 23, 88.46%) and least resistant to erythromycin (n = 2, 7.69%). Escherichia coli isolates (n = 5) were resistant to tetracycline (n = 5, 100%) and ampicillin (n = 5, 100%) but were sensitive to meropenem (n = 5, 100%). Pseudomonas aeruginosa isolates (n = 8) were most resistant to meropenem (n = 3, 37.50%) and to a lesser ciprofloxacin (n = 2, 25%), gentamicin (n = 2, 25%) and ceftazidime (n = 2, 25%). Multi-drug resistant methicillin resistant Staphylococcus aureus (MRSA), cephalosporin resistant Escherichia coli. and carbapenem resistant Pseudomonas aeruginosa were four (n = 4, 15.38%), two (n = 2, 40%) and two (n = 2, 25%) respectively. ESBL (blaCTX-M) and mecA genes were implicated in the resistance mechanism of Escherichia coli and MRSA, respectively.. The findings show presence of MDR isolates from LF patients presenting with chronic wounds; thus, the need to prioritize resistance of MDR bacteria into treatment strategies optimizing morbidity management protocols. This could guide antibiotic selection for treating LF patients presenting with ADLA.

Topics: Amoxicillin; Ampicillin; Anti-Bacterial Agents; Bacteria; beta-Lactamases; Ceftazidime; Chloramphenicol; Ciprofloxacin; Elephantiasis, Filarial; Erythromycin; Escherichia coli; Escherichia coli Infections; Gentamicins; Ghana; Humans; Infant; Meropenem; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Penicillins; Pseudomonas aeruginosa; Staphylococcal Infections; Staphylococcus aureus; Tetracyclines

This experiment was carried out to provide a basis for the treatment of clinical bloodstream infections by analyzing the drug resistance characteristics and integrated gene distribution of Escherichia coli in bloodstream infections in elderly patients. For this aim, E. coli were collected for bacterial identification and drug sensitivity testing from bloodstream infections in elderly patients in the hospital from January 2016 to December 2019. ESBLs positive strains were assayed for genotypes and their integron carriage rates by PCR amplification. The characteristics and differences of various genotype rates were compared and analyzed. Results showed that a total of 230 E. coli strains were isolated. The detection rate of ESBLs-producing bacteria was 37.39 %. ESBLs-producing E. coli showed a high rate of resistance to cefepime, levofloxacin, cotrimoxazole, and ticarcillin/clavulanic acid (>40%). The resistance rate of 230 strains of E. coli to meropenem, minocycline, amikacin, gentamicin and cefoxitin was less than 20%. Among the ESBLs-producing E. coli in bloodstream infections in elderly patients, CTX-M-9 accounted for 27.91%, CTX-M-2 for 17.44%, and SHV for 13.95%. The detection rate of type I integrated genes was 41.30%, and type II and III integrated genes were not detected. ESBLs-producing genotyping-positive bacteria were detected with more than 50% of type I integrated genes. It was concluded that type I integrated genes in ESBLs-producing E. coli isolated from elderly patients carried resistance genes such as CTX-M-9 and CTX-M-2 aggravating multi-drug resistance in bacteria.

Topics: Aged; Amikacin; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cefoxitin; Clavulanic Acid; Drug Resistance; Escherichia coli; Escherichia coli Infections; Gentamicins; Humans; Integrons; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Minocycline; Sepsis; Ticarcillin; Trimethoprim, Sulfamethoxazole Drug Combination

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Bacterial co-infections are associated with unfavourable outcomes in respiratory viral infections; however, microbiological and antibiotic data related to COVID-19 are sparse. Adequate use of antibiotics in line with antibiotic stewardship (ABS) principles is warranted during the pandemic. We performed a retrospective study of clinical and microbiological characteristics of 140 COVID-19 patients admitted between February and April 2020 to a German University hospital, with a focus on bacterial co-infections and antimicrobial therapy. The final date of follow-up was 6 May 2020. Clinical data of 140 COVID-19 patients were recorded: The median age was 63.5 (range 17-99) years; 64% were males. According to the implemented local ABS guidelines, the most commonly used antibiotic regimen was ampicillin/sulbactam (41.5%) with a median duration of 6 (range 1-13) days. Urinary antigen tests for Legionella pneumophila and Streptococcus peumoniae were negative in all cases. In critically ill patients admitted to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were detected. Blood cultures collected at admission showed a diagnostic yield of 4.2%. Bacterial and fungal co-infections are rare in COVID-19 patients and are mainly prevalent in critically ill patients. Further studies are needed to assess the impact of antimicrobial therapy on therapeutic outcome in COVID-19 patients to prevent antimicrobial overuse. ABS guidelines could help in optimising the management of COVID-19. Investigation of microbial patterns of infectious complications in critically ill COVID-19 patients is also required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; Antifungal Agents; Antimicrobial Stewardship; Aspergillosis; Azithromycin; Bacterial Infections; Cohort Studies; Coinfection; COVID-19; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Germany; Humans; Klebsiella Infections; Linezolid; Male; Meropenem; Middle Aged; Piperacillin, Tazobactam Drug Combination; Practice Patterns, Physicians'; Retrospective Studies; SARS-CoV-2; Staphylococcal Infections; Streptococcal Infections; Sulbactam; Vancomycin; Young Adult

Extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC) are a growing threat. Leading ESCREC lineages include sequence type ST131, especially its (bla

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Genotype; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Phylogeny; Sisomicin; Young Adult

Limited therapeutic options exist for treating severe infections caused by multidrug-resistant (MDR) and extensively drug-resistant Gram-negative bacteria (GNB). In this study, the activity of colistin (COL) as monotherapy and in combination with other antibiotics against Acinetobacter baumannii in vitro was investigated. In addition, the efficacy of intravenous colistimethate sodium (CMS) was evaluated in a murine model of urinary tract infection (UTI) induced by MDR Escherichia coli.. Minimum inhibitory concentration (MIC), Monte Carlo simulation, fractional inhibitory concentration index (FICI), time-kill study and erythrocyte lysis assay were applied to evaluate the effect and cytotoxicity of COL, meropenem, imipenem, doripenem (DOR) and sulbactam alone and in combination. For the in vivo experiment, determination of the bacterial burden and histopathological examination were performed to evaluate the efficacy of CMS against UTI.. Of 106 A. baumannii isolates, 104 (98.1%) were susceptible to COL. In the chequerboard assay, COL + DOR showed the highest rate of synergism (60%). No antagonism or cytotoxicity was observed. All COL-based combinations were able to inhibit or slow bacterial re-growth in a time-kill assay. In an in vivo activity study, intravenous CMS reduced not only the bacterial load but also inflammation and maintained structural integrity of infected bladders and kidneys.. The effectiveness of COL alone in vitro and in vivo suggested that intravenous CMS will be an effective and available therapeutic strategy for UTI due to MDR-GNB. In-depth in vitro tests demonstrated that COL + DOR could be an attractive option, especially when the COL MIC is ≥1 μg/mL.

Topics: Acinetobacter baumannii; Administration, Intravenous; Animals; Anti-Bacterial Agents; Biofilms; Colistin; Disease Models, Animal; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Meropenem; Mice; Microbial Sensitivity Tests; Monte Carlo Method; Sulbactam; Treatment Outcome; Urinary Tract Infections

Infection with Shiga toxin-producing Escherichia coli (STEC) results in hemorrhagic colitis and can lead to life-threatening sequelae including hemolytic uremic syndrome (HUS). Conventional treatment is intravenous fluid volume expansion. Antibiotic treatment is contraindicated, due in part to the elevated risk of HUS related to increased Shiga toxin (Stx) release associated with some antibiotics. Given the lack of effective strategies and the increasing number of STEC outbreaks, new treatment approaches are critically needed. In this study, we used an antimicrobial peptide wrwycr, previously shown to enhance STEC killing without increasing Stx production, in combination with antibiotic treatments. Checkerboard and time-kill assays were used to assess peptide wrwycr-antibiotic combinations for synergistic STEC killing. Cytotoxicity and real-time PCR were used to evaluate Stx production and stx expression, respectively, associated with these combinations. The synergistic combinations that showed rapid killing, no growth recovery and minimal Stx production were peptide wrwycr-kanamycin/gentamicin. Transmission electron microscopy revealed striking differences in bacterial cell morphology associated with various treatments. This study provides proof of principle for the design of an antibiotic-peptide wrwycr combination effective in killing STEC without enhancing release of Shiga toxins. It also offers a strategy for the repurposing of antibiotics for treatment of STEC infection.

Topics: Anti-Bacterial Agents; Chloramphenicol; Ciprofloxacin; Drug Synergism; Drug Therapy, Combination; Escherichia coli Infections; Escherichia coli O157; Gentamicins; Humans; Kanamycin; Meropenem; Microbial Sensitivity Tests; Pore Forming Cytotoxic Proteins; Real-Time Polymerase Chain Reaction

Escherichia coli ST131 clone and H30-R/H30-Rx subclones are the most common multidrug-resistant high-risk clones in UTIs. Antimicrobial susceptibility of fosfomycin was compared to five other agents in consecutively collected 299 urinary isolates using the agar dilution method. Prevalence of the ST131 clone and the occurrence of blaCTX-M were also investigated. Overall resistance to fosfomycin, cefuroxime, and ceftriaxone were 2.7%, 35.4%, and 30.1% respectively. fosA, fosA3, and fosC2 genes were not detected. In isolates resistant to ciprofloxacin (34.7%), the prevalence of ST131 clone was 31.7%, of which 81.8% belonged to H30-R and 66.7% to H30-Rx subclones. None of the isolates of the ST131 clone were resistant to fosfomycin. However, bla

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactamases; Ceftriaxone; Cefuroxime; Ciprofloxacin; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Fosfomycin; Humans; Meropenem; Microbial Sensitivity Tests; Polymerase Chain Reaction; Prevalence; Urinary Tract Infections; Virulence Factors

Escherichia coli is the most common cause of Gram-negative prosthetic joint infections (PJIs) and ciprofloxacin is the first-line antibiofilm antibiotic. Due to the emergence of fluoroquinolone resistance, management of E. coli PJIs has become challenging and is associated with high treatment failure rates. We evaluated the efficacy of a newly isolated bacteriophage ɸWL-3 as a therapeutic agent in combination with ciprofloxacin, fosfomycin, gentamicin, meropenem or ceftriaxone against biofilm of a ciprofloxacin/ceftriaxone-resistant E. coli strain and the ATCC 25922 reference strain. ɸWL-3 was first characterised in terms of virion morphology, absorption rate, burst size and killing kinetics against both E. coli strains. The tested antibiotics presented high inhibitory concentrations (ranging from 16 to >1024 μg/mL) when tested alone against biofilms. Co-administration of ɸWL-3 with antibiotics improved the antibiotic efficacy against biofilm, especially after staggered exposure, reducing the minimum biofilm bactericidal concentration (MBBC) up to 512 times. The in vivo antimicrobial activity of ɸWL-3/fosfomycin combination against both E. coli strains was assessed in a Galleria mellonella invertebrate infection model. Treatment of infected larvae after lethal doses of E. coli resulted in enhanced survival rates when combinatorial therapy with ɸWL-3/fosfomycin was applied on E. coli ATCC 25922-infected larvae compared with monotherapy, but not for EC1-infected larvae, which we speculated could be due to higher release of endotoxins in a shorter period in EC1-infected larvae exposed to ɸWL-3. Our study provides new insights into the use of bacteriophages and antibiotics in the treatment of biofilm-associated infections caused by antibiotic-resistant bacteria.

Topics: Animals; Anti-Bacterial Agents; Bacteriophages; Biofilms; Ceftriaxone; Ciprofloxacin; Combined Modality Therapy; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Fosfomycin; Gentamicins; Meropenem; Microbial Sensitivity Tests; Moths; Phage Therapy; Prosthesis-Related Infections

Enterobacterales resistant to carbapenems, a class of last-resort antimicrobials, are ranked as an "urgent" and "critical" public health hazard by CDC and WHO. IMP-type carbapenemase-containing Enterobacterales are endemic in Japan, and blaIMP-6 is one of the notable carbapenemase genes responsible for the resistance. The gene is plasmid-encoded and confers resistance to meropenem, but not to imipenem. Therefore, IMP-6-producing Enterobacterales isolates are occasionally overlooked in clinical laboratories and are referred to as 'stealth-type'. Since previous reports in Japan were confined only to some geographical regions, their distribution across prefectures and the factors affecting the distribution remain unclear. Here, we revealed the dynamics of the geographical distribution of Enterobacterales with IMP-6 phenotype associated with antimicrobial use in Japan. We utilized comprehensive national surveillance data of all routine bacteriological test results from more than 1,400 hospitals in 2015 and 2016 to enumerate Escherichia coli and Klebsiella pneumoniae isolates with the antimicrobial susceptibility pattern (phenotype) characteristic of IMP-6 (imipenem susceptible, meropenem resistant), and to tabulate the frequency of isolates with the phenotype for each prefecture. Isolates were detected in approximately half of all prefectures, and combined analysis with the national data of antimicrobial usage revealed a statistically significant association between the frequency and usage of not carbapenems but third-generation cephalosporins (p = 0.006, logistic mixed-effect regression) and a weaker association between the frequency and usage of fluoroquinolones (p = 0.043). The usage of third-generation cephalosporins and fluoroquinolones may select the strains with the IMP-6 phenotype, and contribute to their occasional spread. We expect the findings will promote antimicrobial stewardship to reduce the spread of the notable carbapenemase gene.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Drug Resistance, Bacterial; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Humans; Imipenem; Japan; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Phenotype

The aim was to evaluate different methods for testing carbapenem susceptibility of Escherichia coli producing KPC-type carbapenemase.. Susceptibility to imipenem, meropenem and ertapenem was assayed using the reference broth microdilution method and several commercial methods (Vitek2, MicroScan, Etest, MIC Test Strip) starting from the same bacterial suspension. Susceptibility to imipenem and meropenem was also tested by Sensititre and disc diffusion (Bio-Rad). Results were interpreted according to EUCAST clinical breakpoints. Essential agreement (EA), category agreement (CA) and error rates were calculated as described by the International Organization for Standardization (ISO) guidelines and also considering the new EUCAST definitions. Genotypic diversity of isolates was evaluated with a RAPD profiling protocol.. Of 54 KPC-positive E. coli isolates, 5.6%, 7.4% and 0% were susceptible standard dosing regimen (S), 55.6%, 72.2% and 0% susceptible increased exposure (I), and 38.9%, 20.4% and 100.0% resistant (R) to imipenem, meropenem and ertapenem, respectively, using the reference broth microdilution method. CA lower than 90% were observed with all systems for imipenem and meropenem using both the ISO and the modified EUCAST criteria. With ertapenem, CA >90% was observed with all methods except Vitek2. RAPD profiling revealed a remarkable genotypic diversity of the isolates, supporting that results were not biased by an oligoclonal nature of the collection.. Commercial methods can be unreliable for testing susceptibility to carbapenems of KPC-producing E. coli. Susceptibility should be confirmed by reference broth microdilution.

Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Diagnostic Errors; Ertapenem; Escherichia coli; Escherichia coli Infections; Genotype; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Molecular Typing; Random Amplified Polymorphic DNA Technique

Drug resistance traits are rapidly disseminated across bacteria by horizontal gene transfer, especially through plasmids. Plasmid curing agents that are active both in vitro and in vivo will resensitize Multi Drug Resistant (MDR) bacteria to antimicrobial agents. Pectin capped platinum nanoparticles (PtNPs) at sub MIC (20 µM) concentration was effective, in causing loss of Extended Spectrum Beta Lactamase (ESBL) harboring plasmid as evidenced by, absence of plasmid in agarose gel and by a concomitant (16-64 fold) drop in MIC for cell wall inhibitors ceftriaxone and meropenem, in carbapenem resistant Escherichia coli (CREC). Interestingly, the plasmid cured strain exhibited small colony morphology and displayed slower growth both in vitro and in vivo. Complementation of cured strain with plasmid from the wild type strain restored resistance towards meropenem and ceftriaxone. Relative to wild type, plasmid cured strain displayed 50% reduction in biofilm formation. Plasmid curing also occurred in vivo in infected zebrafish with curing efficiency of 17% for nanoparticle + meropenem treatment. PtNPs + meropenem reduced bioburden of CREC in infected zebrafish by 2.4 log CFU. Mechanistic studies revealed that nanoparticle interacted with cell surface and perturbed inner membrane integrity. PtNPs did not induce ROS, yet it caused plasmid DNA cleavage, as evidenced by gyrase inhibition assay. Our study for the first time reveals that PtNPs as plasmid curing agent can resensitize MDR bacteria to selective antimicrobial agents in vivo.

Topics: Animals; Anti-Bacterial Agents; Biofilms; Ceftriaxone; Cell Membrane; Disease Models, Animal; DNA Cleavage; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Gene Transfer, Horizontal; Humans; Meropenem; Metal Nanoparticles; Microbial Sensitivity Tests; Plasmids; Platinum; Zebrafish

A rapid and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was developed for quantification of 7 antibiotics in low sample volumes (50 μL): amoxicillin, azithromycin, cefotaxime, ciprofloxacin, meropenem, metronidazole and piperacillin, for both routine monitoring and pharmacokinetic studies. After protein precipitation by acetonitrile, the antibiotics were separated on an Acquity UPLC HSS T3 column (run time, 4 min). The mobile phase consisted of a mixture of (A) ammonium acetate (pH 2.4; 5 mM) and (B) acetonitrile acidified with 0.1% formic acid, delivered at 500 μl/min in a gradient elution mode. Total time run was 2.75 min. Ions were detected in the turbo-ion-spray-positive and multiple-reaction-monitoring modes. The assay was accurate and reproductible for the quantification of the seven antibiotics in serum samples over large concentration ranges.

Topics: Adolescent; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Blood Chemical Analysis; Calibration; Cefotaxime; Child; Child, Preschool; Chromatography, High Pressure Liquid; Ciprofloxacin; Escherichia coli Infections; Humans; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Limit of Detection; Male; Meropenem; Metronidazole; Pediatrics; Piperacillin; Reproducibility of Results; Tandem Mass Spectrometry

The efficacy of empirical non-carbapenem antibiotics for extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia (ESBL-B) is still inconclusive. We conducted a multicenter retrospective cohort study to evaluate the efficacy of empirical non-carbapenem antibiotics for treating ESBL-B. Electronic medical records of individuals who were diagnosed with ESBL-B were reviewed between January 2010 and December 2014 at four university hospitals in Korea. Patients were classified into non-carbapenem and carbapenem groups according to the empirical antibiotic regimen. Patients treated with appropriate empirical antibiotics and who subsequently received carbapenems as definitive therapy were included in the analysis. The inverse probability of treatment weights, a statistical method that adjusts baseline statistics by giving weights based on propensity score, was used. During the study period, 232 adequately treated patients with ESBL-B were included in the analysis: 49 patients in the non-carbapenem group and 183 in the carbapenem group. The baseline characteristics and severity of infection were similar after propensity score weighting. The 30-day mortality rates for the two groups were not statistically significantly different (non-carbapenems 6.3% and carbapenems 11.4%; P = 0.42). In a multivariate analysis, empirical treatment with non-carbapenem antibiotics was not associated with 30-day all-cause mortality (HR 1.02, 95% CI 0.99-1.06, P = 0.14). In a subgroup analysis, empirical treatment with piperacillin-tazobactam was also not associated with 30-day all-cause mortality (HR 1.21, 95% CI 0.37-4.00, P = 0.75). Appropriate non-carbapenems were not inferior to carbapenems as initial empirical therapy for ESBL-B.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Carbapenem-Resistant Enterobacteriaceae; Ciprofloxacin; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Propensity Score; Retrospective Studies; Tertiary Care Centers; Thienamycins; Treatment Outcome

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamase Inhibitors; Escherichia coli; Escherichia coli Infections; Humans; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Thienamycins

Carbapenemase-producing Escherichia coli are a major clinical concern. The current study aimed to identify NDM-5-producing E. coli associated with community-acquired urinary tract infections (UTIs) co-harbouring extended-spectrum β-lactamases (ESBLs) and showing a phenomenon of imipenem minimum inhibitory concentration (MIC) creep.. A total of 973 urine samples were collected from females aged between 18-49 years diagnosed with UTI in Northeast India (June 2014-July 2016). Isolates were identified by standard microbiological methods. The presence of bla. This study observed a unique phenotype of NDM-producers that has not been reported previously. The observed phenomenon poses a global threat as these pathogens may evade phenotypic screening by routine laboratories.

Topics: Adult; beta-Lactamases; Community-Acquired Infections; Ertapenem; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Humans; Imipenem; India; Meropenem; Microbial Sensitivity Tests; Middle Aged; Molecular Typing; Plasmids; Urinary Tract Infections; Young Adult

Topics: Animals; Anti-Bacterial Agents; Drug Discovery; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Mice; Microbial Sensitivity Tests; Monobactams; Pyridones; Rats, Sprague-Dawley; Structure-Activity Relationship; Thiazoles

We describe three cases of bloodstream infection caused by colistin-resistant Escherichia coli in patients in a tertiary hospital in Italy, between August 2016 and January 2017. Whole genome sequencing detected the mcr-1 gene in three isolated strains belonging to different sequence types (STs). This occurrence of three cases with mcr-1-positive E. coli belonging to different STs in six months suggests a widespread problem in settings where high multidrug resistance is endemic such as in Italy.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Humans; Italy; Meropenem; Microbial Sensitivity Tests; Molecular Typing; Sequence Analysis, DNA; Thienamycins; Treatment Outcome

Topics: Adult; Anemia, Hemolytic; Anti-Bacterial Agents; Diagnosis, Differential; Escherichia coli Infections; Female; Hemolytic-Uremic Syndrome; Humans; Meropenem; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic; Sepsis

Ciprofloxacin, meropenem, fosfomycin, and polymyxin B strongly increase production of outer membrane vesicles (OMVs) in

Topics: Anti-Bacterial Agents; Cell Membrane Structures; Ciprofloxacin; Escherichia coli Infections; Escherichia coli O104; Escherichia coli O157; Fosfomycin; Hemolytic-Uremic Syndrome; Humans; Meropenem; Microbial Sensitivity Tests; Polymyxin B; Shiga Toxin 2; Thienamycins

Escherichia coli Ec36 was recovered from a patient in Portugal after treatment with meropenem and colistin. Besides an IncF plasmid with Tn1441d-bla

Topics: Anti-Bacterial Agents; beta-Lactamases; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Genotype; Humans; Meropenem; Microbial Sensitivity Tests; Portugal; Serogroup; Thienamycins

To identify frequency of uropathogenic Escherichia coli and its antibiotic susceptibility pattern.. This cross-sectional study was conducted at Khyber Teaching Hospital, Peshawar, Pakistan, from January 2014 to September 2015, and comprised urine specimens. Biochemical techniques were used to identify Escherichia coli and antibiotic susceptibility was determined by Kirby-Bauer disk diffusion and minimum inhibitory concentration methods. SPSS 23 was used for data analysis.. Of the 787 urine samples, 458(58.2%) grew significant positive growths. Escherichia coli growths were present in 351(76.6%) positive cultures of which 108(30.8%) came from males and 243(69.2%) from female patients. Resistance to fluoroquinolones tested was almost similar (p>0.05). Escherichia coli was highly sensitive to imipenem (98.6%), meropenem (97.8%), tazobactum (96.2%), cefoperazone+sulbactam (93.9%) and amikacin(92.5%).. Escherichia coli was a common pathogen causing urinary tract infections and was highly sensitive to imipenem, meropenem, tazobactum, cefoperazone+sulbactam and amikacin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amikacin; Anti-Bacterial Agents; Cefoperazone; Child; Child, Preschool; Cross-Sectional Studies; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Fluoroquinolones; Humans; Imipenem; Infant; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Sulbactam; Tazobactam; Urinary Tract Infections; Young Adult

Topics: Adolescent; Adult; Amikacin; Anti-Bacterial Agents; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Nitrofurantoin; Urinary Tract Infections; Young Adult

Spontaneous bacterial peritonitis (SBP) can be life threatening in patients with liver cirrhosis. In contrast to community-acquired SBP, no standard treatment has been established for healthcare-related and nosocomial SBP.. We prospectively collected healthcare-related and nosocomial SBP cases from March 2012 till February 2016 at the Department of Internal Medicine I of the University of Bonn and analysed the prevalence of antibiotic resistance among the isolated bacteria. SBP was diagnosed according to international guidelines. Ciprofloxacin, ceftriaxone and meropenem were used as reference substance for resistance to quinolones, third-generation cephalosporins and carbapenems, respectively.. Ninety-two SBP episodes in 86 patients were identified: 63 episodes (69%) were nosocomial. Escherichia coli, Klebsiella species, enterococci and streptococci were most frequently isolated. Frequencies of these microorganisms were comparable for healthcare-related and nosocomial SBP (14% vs. 11%, 14% vs. 8%, 14% vs. 5% and 10% vs. 6%, respectively). In general, antibiotic resistance was higher in isolates from nosocomial than from healthcare-related SBP (50% vs. 18% for quinolones, 30% vs. 11% for piperacillin-tazobactam; P > 0·05), but comparable concerning third-generation cephalosporins (30% vs. 33%). All microorganisms were sensitive to carbapenems apart from nosocomial infections with Enterococcus faecium (n = 3) and Candida albicans (n = 1) due to intrinsic resistance or lack of microbiological efficacy, respectively. No multidrug-resistant microorganisms were detected. Resistance to initial antibiotic treatment affected 30-day survival negatively (18% vs. 68%; P = 0·002).. Resistance to initial antibiotic treatment was associated with increased mortality. With resistance to cephalosporins being frequent, piperacillin-tazobactam or carbapenems might be preferred as treatment of SBP.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Ciprofloxacin; Cross Infection; Drug Resistance, Bacterial; Enterococcus; Escherichia coli Infections; Female; Gram-Positive Bacterial Infections; Humans; Klebsiella Infections; Liver Cirrhosis; Male; Meropenem; Middle Aged; Peritonitis; Prospective Studies; Streptococcal Infections; Thienamycins

Urinary tract infections (UTIs) are a common reason for empirical treatment with broad-spectrum antibiotics worldwide. However, population-based antimicrobial resistance (AMR) prevalence data to inform empirical treatment choice are lacking in many regions, because of limited surveillance capacity. We aimed to assess the prevalence of AMR to commonly used antimicrobial drugs in Escherichia coli and Klebsiella pneumoniae isolated from patients with community- or healthcare-associated UTIs on two islands of Indonesia.. We performed a cross-sectional patient-based study in public and private hospitals and clinics between April 2014 and May 2015. We screened patients for symptoms of UTIs and through urine dipstick analysis. Urine culture and susceptibility testing were supported by telemicrobiology and interactive virtual laboratory rounds. Surveillance data were entered in forms on mobile phones.. Of 3424 eligible patients, 3380 (98.7%) were included in the final analysis, and yielded 840 positive cultures and antimicrobial susceptibility data for 657 E. coli and K. pneumoniae isolates. Fosfomycin was the single oral treatment option with resistance prevalence <20% in both E. coli and K. pneumoniae in community settings. Tigecycline and fosfomycin were the only options for treatment of catheter-associated UTIs with resistance prevalence <20%, whilst the prevalence of resistance to meropenem was 21.3% in K. pneumoniae .. Patient-based surveillance of AMR in E. coli and K. pneumoniae causing UTIs indicates that resistance to the commonly available empirical treatment options is high in Indonesia. Smart AMR surveillance strategies are needed to inform policy makers and to guide interventions.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Catheter-Related Infections; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Epidemiological Monitoring; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Indonesia; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Minocycline; Population Surveillance; Tertiary Care Centers; Thienamycins; Tigecycline; Urinary Tract Infections; Young Adult

Extended-spectrum β-lactamase (ESBL)-producing

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Carbapenems; Critical Care; Doripenem; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Gene Expression; Genotype; Humans; Imipenem; Klebsiella; Klebsiella Infections; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Multilocus Sequence Typing; Thienamycins; United States

The prevalence of extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in nursing home residents has rarely been reported in Taiwan.. A retrospective study was performed at medical wards of a district hospital at southern Taiwan between July 2009 and June 2011. Patients were included if they were older than 18 years, admitted via the emergency department, and their blood, sputum, or urine culture revealed the growth of Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. From each patient only the first isolate from the infection site was included. Antimicrobial susceptibility was determined using the disc diffusion method.. Overall, 827 patients were included, with 354 (42.8%) coming from the community and 473 (57.2%) referred from a nursing home. Of the isolates acquired in nursing home, 45.5% (215/473) harbored ESBL. By contrast, 20.6% (73) of 354 isolates acquired in the community exhibited the ESBL production phenotype (p < 0.001). Of the isolates obtained from blood, urine, or sputum, 28.2% (37/131), 36.0% (208/578), or 36.4% (43/118) harbored ESBL, respectively, whereas 41% (211) of 515 E. coli isolates, 34.3% (72) of 210 K. pneumoniae, and 4.9% (5) of 102 P. mirabilis had ESBL. In general, the isolates from a nursing home or those with ESBL had lower antimicrobial susceptibility rates than those from the community or those without ESBL production. Only amikacin, piperacillin/tazobactam, ertapenem, and imipenem/meropenem were active against >90% Enterobacteriaceae isolates, irrespective of ESBL production.. ESBL production was common among clinical Enterobacteriaceae isolates, especially E. coli or those isolated from nursing home residents.

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Blood; Drug Resistance, Multiple, Bacterial; Emergency Service, Hospital; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Nursing Homes; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Proteus Infections; Proteus mirabilis; Retrospective Studies; Sputum; Taiwan; Thienamycins; Urine

Transplant recipients are at high risk of infections caused by multidrug resistant microorganisms. Due to the limited therapeutic options, innovative antimicrobial combinations against carbapenem-resistant Enterobacteriaceae causing severe infections are necessary.A 61-year-old woman with a history of congenital solitary kidney underwent renal transplantation. The postoperative course was complicated by nosocomial pneumonia due to Stenotrophomonas maltophilia and pan-sensitive Escherichia coli, successfully treated with antimicrobial therapy. On postoperative day 22, diagnosis of surgical site infection and nosocomial pneumonia with concomitant bacteremia due to a Klebisella pneumoniae carbapenemase-producer E coli was made. The patient was treated with the double-carbapenem regimen (high dose of meropenem plus ertapenem) and a potent synergistic and bactericidal activity of this un-conventional therapeutic strategy was observed in vitro. Despite a microbiological response with prompt negativity of blood cultures, the patient faced a worse outcome because of severe hemorrhagic shock.The double-carbapenem regimen might be considered as a rescue therapy in those subjects, including transplant recipients, in whom previous antimicrobial combinations failed or when colistin use might be discouraged. Performing in vitro synergy testing should be strongly encouraged in cases of infections caused by pan-drug resistant strains, especially in high-risk patients.

Topics: Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; beta-Lactams; Carbapenems; Cross Infection; Drug Resistance, Bacterial; Drug Synergism; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Kidney Transplantation; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Surgical Wound Infection; Thienamycins

Neonatal conjunctivitis is the most common occular disease in neonates. Most infections are acquired during vaginal delivery. In spite most of these cases are benign; some of them may progress to systemic complications like loss of vision if left untreated. The authors present a case of a newborn who developed late onset neonatal sepsis from E. coli positive conjunctivitis. The baby was treated with Injection Meropenem and Injection Amikacin for 10 days. The course was uneventful, after that baby responded well and discharged home on 24th day.

Topics: Amikacin; Anti-Bacterial Agents; Conjunctivitis; Escherichia coli; Escherichia coli Infections; Humans; Infant, Newborn; Male; Meropenem; Sepsis; Thienamycins; Treatment Outcome

New Delhi metallo-β-lactamase (NDM) is a serious challenge to the treatment of infections and public health. Serbia has been designated as an endemic region for isolates carrying the bla

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Typing Techniques; beta-Lactam Resistance; beta-Lactamases; Cloning, Molecular; Conjugation, Genetic; Escherichia coli; Escherichia coli Infections; Gene Expression; Humans; Leukemia; Male; Meropenem; Plasmids; Thienamycins

To find the most prevalent organism in diabetic foot ulcers and its drug sensitivity and resistance to different standard antibiotics.. Adescriptive and cross-sectional study.. Ward 7, Jinnah Postgraduate Medical Center, Karachi, from December 2010 to December 2012.. Ninety-five diabetic patients with infected foot wounds of Wegener grade 2 - 5 who had not received any previous antibiotics were included in the study by consecutive sampling. Pus culture specimen from wounds was taken and the organism isolated was identified. Also the most sensitive group of antibiotics and the most resistant one to that organism was noted.. Staphylococcus aureuswas the most prevalent organism constituting 23.16% (n=22) of the organisms isolated; Escherichia coli with 17.89% (n=17) and Klebsiella with 12.63% (n=12) followed. Males presented more with diabetic foot (n=52) out of 95 patients. The most common age group affected was 41 - 60 years (73 patients). The organisms were most sensitive to Meropenem, effective in 90 (95%) patients and most resistant to Cotrimoxazole (80, 84% patients). Out of the 95 patients, 39 (41%) patients were hypertensive, 30 (31.5%) were obese and 14 (15%) were smokers. Staphylococcus aureus was the most prevalent organism overall irrespective to gender, age groups and co-morbidity of the patients.. Staphylococcus aureuswas the most frequent organism in diabetic foot ulcers; the most effective antibiotic is Meropenem and least effective is Cotrimoxazole.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Cross-Sectional Studies; Diabetic Foot; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella; Klebsiella Infections; Meropenem; Microbial Sensitivity Tests; Middle Aged; Pakistan; Prevalence; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Wound Infection

Infection is a major determinant of clinical outcome among patients in the intensive care unit. However, these data are lacking in most developing countries; hence, we set out to describe the profile of nosocomial infection in one of the major tertiary hospitals in northern Nigeria.. Case records of patients who were admitted into the intensive care unit over a 4-year period were retrospectively reviewed. A preformed questionnaire was administered, and data on clinical and microbiological profile of patients with documented infection were obtained.. Eighty-our episodes of nosocomial infections were identified in 76 patients. Road traffic accident (29/76, 38.2%) was the leading cause of admission. The most common infections were skin and soft tissue infections (30/84, 35.7%) followed by urinary tract infection (23/84, 27.4%). The most frequent isolates were Staphylococcus aureus (35/84, 41.7%), Klebsiella pneumoniae (18/84, 21.4%), and Escherichia coli (13/84, 15.5%). High rate of resistance to cloxacillin (19/35, 54.3%) and cotrimoxazole (17/26, 65.4%) was noted among the S aureus isolates. All the Enterobacteriaceae isolates were susceptible to meropenem, whereas resistance rate to ceftriaxone was high (E coli, 55.6%; K pneumoniae, 71.4%; Proteus spp, 50%).. Infection control practice and measures to curtail the emergence of antimicrobial resistance need to be improved.

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Catheter-Related Infections; Ceftriaxone; Cloxacillin; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Nigeria; Pneumonia, Bacterial; Retrospective Studies; Staphylococcal Infections; Staphylococcus aureus; Surgical Wound Infection; Tertiary Care Centers; Thienamycins; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Young Adult

Eravacycline (formerly TP-434) was evaluated in vitro against pre-established biofilms formed by a uropathogenic Escherichia coli strain. Biofilms were eradicated by 0.5 μg/ml eravacycline, which was within 2-fold of the MIC for planktonic cells. In contrast, colistin and meropenem disrupted biofilms at 32 and 2 μg/ml, respectively, concentrations well above their respective MICs of 0.5 and 0.03 μg/ml. Gentamicin and levofloxacin eradicated biofilms at concentrations within 2-fold of their MICs.

Topics: Anti-Bacterial Agents; Biofilms; Colistin; Colony Count, Microbial; Escherichia coli Infections; Gentamicins; Humans; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Tetracyclines; Thienamycins; Urinary Tract Infections; Uropathogenic Escherichia coli

An increasing incidence of extended-spectrum β-lactamase (ESBL-) producing Escherihia Coli poses a difficult problem for clinicians to establish an optimal strategy for the effective antibiotic treatment of urinary tract infections (UTI).. (1) Fosfomycin/minocycline (FOM/MINO) or rifampicin/sulfamethoxazole-trimethoprim (RFP/ST) combinations and (2) levofloxacin (LVFX) alone were used as an internal medication, and (3) cefoperazone/sulbactam (CPZ/SBT) and (4) meropenem (MEPM) were administered through intravenous injection. The selection of antibiotics was done empirically, according to the history and severity of illness and urinary findings, and the presence of comobidities. The efficacy of the treatment was determined by the absence of any pathogenic bacteria from a urinary culture after treatment.. ESBL-producing and LVFX resistant non-ESBL producing E. coli were detected by an initial urinary culture in 33 and 10%, respectively, of the specimens before treatment. All the ESBL-producing E. Coli colonies were resistant against LVFX. The efficacy of the treatment was 9/11 (82%) in the FOM/MINO-RFP/ST group, 9/14 (64%) in the LVFX group, 9/16 (56%) in the CPZ/SBT group, and 19/27 (70%) in the MEPM group. In the FOM/MINO・RFP/ST group, ESBL-producing E. Coli were detected in the urine before treatment in 5 out of 16 patients and those E. coli disappeared after treatment in all 5 patients. In the LVFX group, the drug was changed to MEPM in 6 out of 15 patients soon after the presence of ESBL-producing/LVFX resistant E. Coli was identified by a urinary culture. In the CPZ/SBT group, ESBL-producing and/or LVFX-resistant E. coli disappeared in 4 out of 6 cases, while they were newly found in post-treatment urine cultures in 2 patients. In the MEPM group, 15 out of 28 patients initially had ESBL-producing/LVFX resistant E. Coli and those drug-resistant E. Coli disappeared from their urine after treatment in all patients. The drug susceptibility test of the urinary culture from all the patients with UTI showed CPZ/SBT-resistant colonies to be found in 19 out of 32 specimens, while AMPC/CVA-resistant ones were found in 9 out of 32 of ESBL-producing E. Coli.. Our present study demonstrates that FOM/MINO or ST combinations were effective in the treatment of ESBL-producing E. Coli in mild cases of UTI and MEPM in severe cases. When using β-lactam/β-lactamase inhibitor combinations, the effect should be ascertained by examining post-treatment urinary specimens, because of the presence of ESBL-producing E. Coli strains which are resistant to those antibiotics.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Meropenem; Middle Aged; Thienamycins; Urinary Tract Infections

Most post-neurosurgical meningitis research has been focused on large cohorts with numerous cases followed over several years. However, the characteristics of post-neurosurgical meningitis in an entire single year are still unclear, and knowledge of these characteristics might influence the selection of appropriate antibiotics and therapeutic strategies for the successful management of this disease. Our aim is to obtain a better understanding of post-neurosurgical meningitis over a single entire year.. Patients with positive meningitis cultures after neurosurgical operations in our hospital during the entire year of 2012 were included in the analysis. We report demographic characteristics, morbidity during different seasons, clinical and bacteriological profiles, sensitivity to antibiotics and causes of the post-neurosurgical meningitis infections in our cohort.. Of the 6407 patients who underwent neurosurgical procedures during the study period, 146 developed post-neurosurgical meningitis and the overall incidence of meningitis was 2.28%. The incidence of meningitis was significantly higher in patients who underwent surgery in the autumn and winter than spring or summer (p=0.000). The most common organisms causing meningitis were Gram-positive bacteria, followed by the Klebsiella and Baumannii species. Compound sulfamethoxazole (52.6%) and vancomycin (10.5%) were the most active antibiotics against Gram-positive bacteria strains, whereas meropenem (43.8%) and polymyxin (18.8%) were active against Gram-negative bacillus strains.. Post-neurosurgical meningitis usually occurs in the autumn and winter of the year in our hospital. Gram-positive organisms, which are sensitive to compound sulfamethoxazole and vancomycin, are the most common causative pathogens of post-neurosurgical meningitis in the northern mainland of China.

Topics: Acinetobacter Infections; Adolescent; Adult; Aged; Anti-Bacterial Agents; Child; Child, Preschool; China; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Male; Meningitis, Bacterial; Meropenem; Middle Aged; Neurosurgical Procedures; Polymyxins; Postoperative Complications; Pseudomonas Infections; Retrospective Studies; Seasons; Staphylococcal Infections; Sulfamethoxazole; Thienamycins; Vancomycin; Young Adult

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae are the leading causes of hospital-associated infections, but community-acquired cases are increasingly being reported. This study determined the prevalence of ESBL-producing E. coli and K. pneumoniae carriers, their bla genes and risk factors of 452 patients admitted to the emergency room (ER) of Ramathibodi Hospital, Mahidol University, Bangkok, Thailand between April and August 2011. Prevalence of ESBL-producing E. coli and K. pneumoniae from rectal swabs was 16.5% and 1.0%, respectively. Factors associated with ESBL-producing carriers were a previous history of hospital admission (p = 0.001) and visits to health care facilities (p = 0.002) during the previous 3 months. All ESBL-producing isolates were susceptible to imipenem, meropenem and ertapenem. The majority (78%) of ESBL-producing E. coli isolates showed very high resistance to cefotaxime and ceftriaxone (MIC50 and MIC90 > 256 µg/ml). ESBL-producing E. coli harbored chromosomal blaTEM (96%), blaCTX-M (70%) and blaSHV (1%), while 8%, 73% and 3%, respectively, were located on plasmid. The prevalence of these genes in ESBL-producing K. pneumoniae was 75%, 50% and 25%, respectively on chromosome; and 100%, 25% and 50%, respectively on plasmid. Nucleotide sequence analysis revealed that these bla genes were of the type blaTEM-1' blaTEM-116' blaCTX-M-15' blaCTX-M-161' blaSHV-12, blaSHV-28 and blaSHV-148. Detailed epidemiologic and clinical characteristics of ER patients with history of prior hospital visits should be carried out to identify the ESBL-producing organisms they have acquired in order to institute appropriate treatment for these patients as well as control measures against further dissemination of these life-threatening organisms.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cross Infection; Emergency Service, Hospital; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Plasmids; Thailand; Thienamycins; Young Adult

Escherichia coli is a rare cause of community-acquired meningitis in adults unless predisposing factors are present (e.g., previous penetrating cranio-cerebral injury or neurosurgery, immunosuppression, chronic alcoholism, history of cancer, diabetes mellitus, advanced age).. We describe the case of a 53-year-old woman, resident in Germany, suffering from community-acquired bacterial meningitis caused by CTX-M-9 type extended spectrum β-lactamase producing Escherichia coli. Because typical predisposing factors were not apparent, pathogen identification resulted in expanded diagnostics to exclude a distant or contiguous primary focus. By magnetic resonance tomography, a previously unrecognized large retropharyngeal abscess with cervical spondylodiscitis was detected. In retrospect, the patient had complained about neck pain for a few weeks prior to meningitis onset, but the symptoms were interpreted as being related to a herniated disk. Meningitis and osteomyelitis resolved completely under surgical treatment and meropenem therapy.. In case of adult Escherichia coli meningitis, underlying diseases should always be carefully excluded, especially if predisposing factors are not apparent.

Topics: beta-Lactamases; Discitis; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Germany; Humans; Magnetic Resonance Imaging; Meningitis, Escherichia coli; Meropenem; Middle Aged; Osteomyelitis; Retropharyngeal Abscess; Thienamycins

The occurrence of community-associated infections due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. These organisms are frequently resistant to many of the antimicrobial agents but remain susceptible to carbapenems. We investigated the in vitro emergence of carbapenem resistance in a collection of clinical isolates of ESBL -producing E. coli.. First and second-step resistant mutants were obtained from E. coli with ESBL. Aliquots of 50 μl containing > 109 CFU were applied to Mueller-Hinton plates containing meropenem, imipenem or ertapenem. MICs for native strains and mutants were determined using the epsilometric test (E-test).. Resistant mutants were not selected with imipenem or meropenem. E. coli growth was observed on ertapenem (0.5 mg/L)-containing plates in 13 of 57 clinical isolates (22.8 %).The ertapenem MIC for these first-step mutants were ≥ 1 mg/L, remaining susceptible to imipenem and meropenem. The first-step mutants were used as native strains. Six second-step resistant mutants were selected with ertapenem. All were fully resistant (CMI ≥ 8 mg/L) to ertapenem, three were resistant to meropenem and one to imipenem. Four second-step resistant mutants were selected with meropenem. All were resistant to ertapenem, meropenem, and two of them were resistant to imipenem.. Stable resistant mutants were easy to select with ertapenem among ESBL-producing E. coli. Two steps were necessary to select resistant mutants to meropenem or imipenem. The use of ertapenem in high-inoculum infections or in undrained focus of infection should be monitored to reduce the risk on selection of resistance.

Topics: Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Drug Resistance, Bacterial; Ertapenem; Escherichia coli; Escherichia coli Infections; Imipenem; Meropenem; Microbial Sensitivity Tests; Mutation; Thienamycins

A 44-year-old Indian national with a prostate-specific antigen of 5.4 ng/mL underwent 12-core transrectal ultrasound-guided prostate biopsies. Following this, he had three hospital admissions with severe urosepsis secondary to extended spectrum β lactamase (ESBL) producing Escherichia coli. He had recurrent sepsis immediately after discontinuation of intravenous meropenem to which the ESBL was sensitive. He proceeded to radical prostatectomy for intermediate-high risk Gleason 7 prostate cancer, while still on intravenous meropenem, 2 months after his biopsy. His prostatectomy involved a difficult dissection due to inflammatory changes and fibrosis after multiple septic episodes. He had complete resolution of infection after surgery with discontinuation of antibiotics on the third postoperative day, without any recurrence of sepsis.

Topics: Adenocarcinoma; Adult; Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli Infections; Humans; Image-Guided Biopsy; Male; Meropenem; Neoplasm Grading; Prostatectomy; Prostatic Neoplasms; Prostatitis; Recurrence; Thienamycins

A 45-year-old man with dilated cardiomyopathy presented with acute leg pain and erythema suggestive of necrotising fasciitis. Initial surgical exploration revealed no necrosis and treatment for a soft tissue infection was started. Blood and tissue cultures unexpectedly grew a Gram-negative bacillus, subsequently identified by an automated broth microdilution phenotyping system as an extended-spectrum β-lactamase producing Escherichia coli. The patient was treated with a 3-week course of antibiotics (ertapenem followed by ciprofloxacin) and debridement for small areas of necrosis, followed by skin grafting. The presence of E. coli triggered investigation of both host and pathogen. The patient was found to have previously undiagnosed liver disease, a risk factor for E. coli soft tissue infection. Whole genome sequencing of isolates from all specimens confirmed they were clonal, of sequence type ST131 and associated with a likely plasmid-associated AmpC (CMY-2), several other resistance genes and a number of virulence factors.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactams; Ciprofloxacin; Diagnosis, Differential; Drug Resistance, Multiple, Bacterial; Ertapenem; Escherichia coli; Escherichia coli Infections; Floxacillin; Follow-Up Studies; Genome, Bacterial; Gentamicins; Humans; Liver Diseases; Male; Meropenem; Middle Aged; Sequence Analysis, DNA; Soft Tissue Infections; Thienamycins; Treatment Outcome; Vancomycin

A liver transplant patient was admitted with cholangitis, for which meropenem therapy was started. Initial cultures showed a carbapenem-susceptible (CS) Escherichia coli strain, but during admission, a carbapenem-resistant (CR) E. coli strain was isolated. Analysis of the outer membrane protein profiles showed that both CS and CR E. coli lacked the porins OmpF and OmpC. Furthermore, PCR and sequence analysis revealed that both CS and CR E. coli possessed bla(CTX-M-15) and bla(OXA-1). The CR E. coli strain additionally harbored bla(CMY-2) and demonstrated a >15-fold increase in β-lactamase activity against nitrocefin, but no hydrolysis of meropenem was detected. However, nitrocefin hydrolysis appeared strongly inhibited by meropenem. Furthermore, the CMY-2 enzyme demonstrated lower electrophoretic mobility after its incubation either in vitro or in vivo with meropenem, indicative of its covalent modification with meropenem. The presence of the acyl-enzyme complex was confirmed by mass spectrometry. By transformation of the CMY-2-encoding plasmid into various E. coli strains, it was established that both porin deficiency and high-level expression of the enzyme were needed to confer meropenem resistance. In conclusion, carbapenem resistance emerged by a combination of elevated β-lactamase production and lack of porin expression. Due to the reduced outer membrane permeability, only small amounts of meropenem can enter the periplasm, where they are trapped but not degraded by the large amount of the β-lactamase. This study, therefore, provides evidence that the mechanism of "trapping" by CMY-2 β-lactamase plays a role in carbapenem resistance.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; beta-Lactamases; Cell Membrane Permeability; Cephalosporins; Drug Resistance, Multiple, Bacterial; Enzyme Activation; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Humans; Hydrolysis; Meropenem; Microbial Sensitivity Tests; Periplasm; Plasmids; Protein Binding; Thienamycins; Young Adult

Resistance to carbapenems is a significant therapeutic threat. The increasing frequency of car bapenemase enzymes among Gram-negative bacilli makes their early detection and differentiation urgent. Carbapenemases belonging to Class A are most commonly produced by members of family Enterobacteriaceae and are inhibited to various degrees by clavulanic acid. The present study is aimed to determine the occurrence and phenotypic detection of Class A carbapenemases in Escherichia coli and Klebsiella pneumoniae blood isolates from septicemic patients.. A total of 75 isolates of K. pneumoniae and 25 E. coli were screened for resistance to carbapenems by using meropenem and imipenem discs and meropenem E-test. Positive strains were then subjected to a modified Hodge test combined with carbapenemase inhibition tests to phenotypically detect and differentiate Class A serine carbapenemases from other classes of carbapenem hydrolyzing enzymes.. The screening test showing the number of isolates resistant to meropenem and imipenem were 41 and 35 for K. pneumoniae and nine and four for E. coli, respectively. A total of 25 (33.3%) K. pneumoniae isolates and two (8.0%) E. coli isolates were classified as Class A carbapenemase producers. Multidrug resistance with coexistence of extended spectrum-beta-lactamases occurred in 44.4% isolates. However, all of the isolates were susceptible to colistin, polymyxin B, and tigecycline by disc diffusion test.. We conclude from the present study that Class A carbapenemases appear to be the predominant cause of resistance to carbapenems in Enterobacteriaceae at our center and, thus, phenotypic detection based on simple methods should be employed routinely in clinical microbiology laboratories.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Cross Infection; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Prevalence; Sepsis; Tertiary Care Centers; Thienamycins

Spontaneous bacterial peritonitis is a common infection in cirrhosis, associated with a high mortality. Third-generation cephalosporins are recommended as first-line treatment. The aim was to evaluate the epidemiology of microbiological ascitic fluid findings and antimicrobial resistance in Denmark.. All patients with cirrhosis and a positive ascitic fluid culture, at three university hospitals in the Copenhagen area during a 7-year period, were retrospectively evaluated. Patients with apparent secondary peritonitis were excluded from the study.. One hundred and forty cases with 187 microbiological isolates were identified. The findings were: Gram-positive cocci, n = 86 (45.9%); Enterobacteriaceae, n = 59 (31.7%), with Escherichia coli identified in 31 cases; anaerobes, n = 14 (7.5%); yeast, n = 12 (6.4%); and cutaneous flora, n = 15 (8.0%). One case of Listeria monocytogenes was identified (0.5%). Overall antibiotic coverage was 57% for cephalosporins, 73% for piperacillin-tazobactam, and 72% for meropenem. Mortality rates in patients with isolates susceptible or resistant to the initial antibiotic treatment at 30 days follow-up were 35% and 55%, respectively (p = 0.017, Log-rank test).. Almost half of the isolates were Gram-positive cocci, and as the overall antibiotic coverage with a cephalosporin was only 57%, and survival significantly dependent on whether the microbial etiology was susceptible to initial antibiotic treatment or not, a change of standard empiric antibiotic regime should be considered. Piperacillin-tazobactam could be a favorable choice.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ascitic Fluid; Cephalosporins; Denmark; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Kaplan-Meier Estimate; Liver Cirrhosis; Male; Meropenem; Middle Aged; Mycoses; Penicillanic Acid; Peritonitis; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Thienamycins

A retrospective study was conducted at two medical centers in Taiwan to evaluate the clinical characteristics, outcomes, and risk factors for mortality among patients treated with a carbapenem for bacteremia caused by extended-spectrum-beta-lactamase (ESBL)-producing organisms. A total of 251 patients with bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates treated by a carbapenem were identified. Among these ESBL-producing isolates, rates of susceptibility to ertapenem (MICs ≤ 0.25 μg/ml) were 83.8% and 76.4%, respectively; those to meropenem were 100% and 99.3%, respectively; and those to imipenem were 100% and 97.9%, respectively. There were no significant differences in the critical illness rate (P = 0.1) or sepsis-related mortality rate (P = 0.2) for patients with bacteremia caused by ESBL-producing K. pneumoniae (140 isolates, 55.8%) and E. coli (111 isolates, 44.2%). Multivariate analysis of variables related to sepsis-related mortality revealed that the presence of severe sepsis (odds ratio [OR], 15.9; 95% confidence interval [CI], 5.84 to 43.34; P < 0.001), hospital-onset bacteremia (OR, 4.65; 95% CI, 1.42 to 15.24; P = 0.01), and ertapenem-nonsusceptible isolates (OR, 5.12; 95% CI, 2.04 to 12.88; P = 0.001) were independent risk factors. The patients receiving inappropriate therapy had a higher sepsis-related mortality than those with appropriate therapy (P = 0.002), irrespective of ertapenem, imipenem, or meropenem therapy. Infections due to the ertapenem-susceptible isolates (MICs ≤ 0.25 μg/ml) were associated with a more favorable outcome than those due to ertapenem-nonsusceptible isolates (MICs > 0.25 μg/ml), if treated by a carbapenem. However, the mortality for patients with bacteremic episodes due to isolates with MICs of ≤ 0.5 μg/ml was similar to the mortality for those whose isolates had MICs of >0.5 μg/ml (P = 0.8). Such a finding supports the rationale of the current CLSI 2011 criteria for carbapenems for Enterobacteriaceae.

Topics: Adult; Bacteremia; beta-Lactams; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Microbial Sensitivity Tests; Retrospective Studies; Thienamycins; Young Adult

Topics: Anti-Bacterial Agents; Emphysema; Escherichia coli Infections; Humans; Male; Meropenem; Middle Aged; Polycystic Kidney, Autosomal Dominant; Thienamycins

A case is presented of a breast-feeding mother receiving meropenem treatment for a postpartum urinary tract infection caused by extended-spectrum beta-lactamase producing Escherichia coli. Five milk samples were collected in a 48-hour period during meropenem therapy. The average and maximum meropenem concentrations in milk were 0.48 and 0.64 µg/mL, respectively. Based on the maximum concentration, the calculated infant daily exposure from breast milk was 97 µg/kg/d, and the infant weight-adjusted percentage of maternal dosage was 0.18%. There were no dermatologic or gastrointestinal side effects noted in the breastfed infant. Meropenem appears to be acceptable to use during breast-feeding.

Topics: Adult; Anti-Bacterial Agents; Breast Feeding; Escherichia coli Infections; Female; Humans; Infant, Newborn; Lactation; Meropenem; Milk, Human; Pregnancy; Thienamycins; Urinary Tract Infections

Carbapenem resistance due to metallo-β-lactamases (MBLs) in Enterobacteriaceae has gained much prominence in recent months. The emergence and subsequent spread of New Delhi metallo-β-lactamase-1 (NDM-1) constitutes a potential threat in terms of the management of affected patients and institutional infection control efforts. We evaluated an in-house prepared meropenem impregnated MacConkey agar versus CHROMagar KPC.. The lowest limit of detection (LLD) was compared for nine clinical isolates of NDM-1 producing Enterobacteriaceae on the above mentioned agar media.. LLD was comparable for all the nine clinical isolates on both media. The cost of the antibiotic impregnated MacConkey agar was considerably lower (US$0.39) as compared to the commercial media, while its performance remained unaltered for a period of at least 8 weeks of storage.. The in-house medium proved to be a suitable and cheap alternative to the CHROMagar KPC.

Topics: Adult; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Culture Media; Drug Stability; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Middle Aged; Thienamycins

Topics: Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Female; Humans; India; Infant; Meropenem; Thienamycins; Travel; Treatment Outcome; Urinary Tract Infections

Topics: Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Bacterial Proteins; beta-Lactamases; Coinfection; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; R Factors; Thienamycins; Urinary Tract Infections

We describe the first report of simultaneous blood infection with KPC-2 producing Klebsiella pneumoniae and Escherichia coli in a Brazilian patient. We highlight the importance of implementing efficient infection control measures to limit the spread of these phenotypes in a hospital setting.

Topics: Aged, 80 and over; Amikacin; Anti-Bacterial Agents; beta-Lactamases; Catheter-Related Infections; Community-Acquired Infections; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Pneumonia, Bacterial; Thienamycins

The imipenem and meropenem-resistant strains Citrobacter freundii HS70 and Escherichia coli HS510 were isolated from patients in Shanghai, China. By isoelectric focusing, PCR amplification and sequencing, these strains were each found to produce four β-lactamases: TEM-1, KPC-3, SHV-7 and CTX-M-14. A conjugation experiment and plasmid restriction digestion revealed that the bla (KPC-3) gene was located on the same plasmid in both isolates. Bidirectional primer walking sequencing showed that the nucleotide sequence surrounding the 3.8 kb bla(KPC-3) contained a 671-bp insertion similar to that previously characterized in China. The insertion was located between the promoter and the coding region of the bla(KPC-3) gene. Susceptibility testing performed on recombinant strains carrying the bla(KPC-3) gene with or without the insertion revealed that minimum inhibitory concentrations of imipenem, meropenem, cefepime, and cefotaxime for E. coli EMU-KPC3 (without insertion) were four times higher than that of E. coli EKPC3 (with insertion). The 671 bp insertion reduced bla(KPC-3) expression significantly. Taken together, these results suggest that KPC-3-producing C. freundii and E. coli have begun to emerge in our hospital.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Carbapenems; China; Citrobacter freundii; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Isoelectric Focusing; Meropenem; Microbial Sensitivity Tests; Middle Aged; Plasmids; Polymerase Chain Reaction; Sequence Analysis, DNA; Thienamycins

Infections caused by extended-spectrum beta-lactamase (ESBL) producing Escherichia coli and Klebsiella spp. constitute severe problems. Carbapenems are commonly used to treat these infections. However, infections caused by carbapenem-resistant gram-negative bacteria show an increasing trend recently. The aim of this study was to investigate the susceptibilities of ESBL-producing E.coli and Klebsiella spp. to ertapenem and other carbapenems. A total of 239 E.coli, 28 K.pneumoniae and 11 K.oxytoca strains isolated from clinical specimens (208 urine, 16 blood, 26 wound, 17 sterile body fluids, four tracheal aspirates and seven others) of hospitalized patients and outpatients between January 2007-February 2008, were included to the study. The isolates were identified by conventional methods, and antibiotic susceptibility tests were performed by Kirby Bauer disc diffusion method according to Clinical and Laboratory Standards Institute (CLSI) standards. ESBL production was tested by double disk diffusion method. When ESBL production was indeterminate, cefotaxime-clavulanic acid E test (BioMerieux, France) was used. According to the CLSI standards modified Hodge test was performed for carbapenem resistant isolates and minimal inhibitory concentration (MIC) values were detected for ertapenem (Etest®, BioMerieux, France), imipenem and meropenem (M.I.C. Evaluator Strips, Oxoid, UK). All of the isolates were found susceptible to amikacin (278/278; 100%), whereas the susceptibility rates for imipenem/meropenem and ertapenem were 99.3% (276/278) and 98.6% (274/278), respectively. When evaluated individually, ertapenem susceptibilities of E.coli, K.pneumoniae and K.oxytoca strains were 99.2%, 96.4% and 90.9%, respectively, while these rates were 100%, 96.4% and 90.9%, respectively, for imipenem/meropenem. Carbapenem resistance was detected in two E.coli, one K.oxytoca and one K.pneumoniae isolates. While two Klebsiella spp. İsolates were resistant to all of the tested carbapenems (MIC > 32 µg/ml), two E.coli isolates were resistant to ertapenem (MIC > 32 µg/ml) but susceptible to imipenem (MIC= 0.25 µg/ml) and meropenem (MIC= 0.5 µg/ml). Carbapenemase production was demonstrated by modified Hodge test in all of the carbapenem-resistant isolates. In conclusion, ESBL-producing gram-negative isolates should be routinely tested with a screening method for carbapenemase activity and confirmation tests should be performed in suspected cases.

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; beta-Lactams; Carbapenems; Ertapenem; Escherichia coli; Escherichia coli Infections; Humans; Imipenem; Klebsiella Infections; Klebsiella oxytoca; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Thienamycins

For 244 patients with bacteremia due to extended-spectrum β-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae treated by ertapenem (73, 29.9%) or either imipenem or meropenem (171, 70.1%), the therapeutic efficacy was evaluated. Ertapenem therapy was effective for patients with ESBL-producing E. coli or K. pneumoniae bacteremia in terms of mortality and microbiological responses, as compared with imipenem or meropenem.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; beta-Lactams; Carbapenems; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Male; Meropenem; Middle Aged; Thienamycins; Treatment Outcome

Emphysematous pyelonephritis (EPN) is a rare, life threatening, upper urinary tract infection with high mortality rate.. We report a type-2 diabetes mellitus patient presenting with persistent fever, vomiting and pyuria despite appropriate treatment, diagnosed as a case of EPN, recovered without any surgical intervention.. Suspicion of EPN should be entertained in diabetes mellitus patient with persistent pyuria and deteriorating condition despite adequate treatment with antibiotics.

Topics: Anti-Infective Agents; Diabetes Mellitus, Type 2; Diagnosis, Differential; Emphysema; Escherichia coli; Escherichia coli Infections; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Meropenem; Metronidazole; Middle Aged; Pyelonephritis; Thienamycins; Tomography, X-Ray Computed; Treatment Outcome; Urinary Tract Infections

There has been a resurgence of interest in the use of colistin for the treatment of multidrug-resistant Gram-negative bacterial infections. A more favorable infection outcome is observed when colistin is used in combination with carbapenems. We present a patient with severe New Delhi metallo-β-lactamase-1 Escherichia coli infection who developed convulsions rapidly followed by acute respiratory muscle weakness and apnoea during treatment with colistin and meropenem. Chromatographic assay showed a "trough" colistin level that was approximately fourfold higher than previously reported maximum steady-state colistin plasma levels in critically ill patients. The patient's renal clearance never necessitated dose adjustments, suggesting that the observed high plasma colistin level might be due to impaired non renal elimination. Although meropenem itself has very low neurotoxic potential, its concomitant use with colistin may have elicited colistin neurotoxicity.

Topics: Anti-Bacterial Agents; Apnea; beta-Lactamases; Chromatography; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Humans; Male; Meropenem; Middle Aged; Plasma; Seizures; Thienamycins

Community-acquired extended-spectrum beta-lactamase E coli (ESBLEC) have not been previously described in Honolulu. Its emergence as a community-acquired pathogen is concerning. This case series describes three patients who were diagnosed with community-acquired ESBLEC bacteriuria in 2010.

Topics: Aged; Aged, 80 and over; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Bacteriuria; beta-Lactamases; Ciprofloxacin; Community-Acquired Infections; Escherichia coli; Escherichia coli Infections; Female; Hawaii; Humans; Male; Meropenem; Middle Aged; Nitrofurantoin; Risk Factors; Thienamycins

All of the carbapenem-resistant Escherichia coli (CREC) isolates identified in our hospital from 2005 to 2008 (n = 10) were studied. CREC isolates were multidrug resistant, all carried bla(KPC-2), and six of them were also extended-spectrum beta-lactamase producers. Pulsed-field gel electrophoresis indicated six genetic clones; within the same clone, similar transferable bla(KPC-2)-containing plasmids were found whereas plasmids differed between clones. Tn4401 elements were identified in all of these plasmids.

Topics: Academic Medical Centers; Bacterial Proteins; Base Sequence; beta-Lactamases; Carbapenems; DNA Primers; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Escherichia coli; Escherichia coli Infections; Humans; In Vitro Techniques; Israel; Microbial Sensitivity Tests; Molecular Epidemiology; Plasmids; Time Factors

Foreign travel has been suggested to be a risk factor for the acquisition of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. To our knowledge, this has not previously been demonstrated in a prospective study. Healthy volunteers traveling outside Northern Europe were enrolled. Rectal swabs and data on potential travel-associated risk factors were collected before and after traveling. A total of 105 volunteers were enrolled. Four of them did not complete the study, and one participant carried ESBL-producing Escherichia coli before travel. Twenty-four of 100 participants with negative pretravel samples were colonized with ESBL-producing Escherichia coli after the trip. All strains produced CTX-M enzymes, mostly CTX-M-15, and some coproduced TEM or SHV enzymes. Coresistance to several antibiotic subclasses was common. Travel to India was associated with the highest risk for the acquisition of ESBLs (88%; n = 7). Gastroenteritis during the trip was an additional risk factor (P = 0.003). Five of 21 volunteers who completed the follow-up after 6 months had persistent colonization with ESBLs. This is the first prospective study demonstrating that international travel is a major risk factor for colonization with ESBL-producing Enterobacteriaceae. Considering the high acquisition rate of 24%, it is obvious that global efforts are needed to meet the emergence and spread of CTX-M enzymes and other antimicrobial resistances.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Lactamases; Child; Child, Preschool; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Sweden; Travel; White People; Young Adult

Topics: Abdominal Abscess; Anti-Bacterial Agents; Drainage; Emphysema; Escherichia coli Infections; Female; Humans; Meropenem; Middle Aged; Portal Vein; Portography; Pyelonephritis; Thienamycins; Tomography, X-Ray Computed; Treatment Outcome

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefoxitin; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; New Zealand; Plasmids

Pyomyositis is an infection of skeletal muscle that involves the formation of intramuscular abscesses. It occurs most commonly in immunocompromised patients. Pyomyositis caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has never been reported in the literature. A 48-year-old female patient developed ESBL-producing E. coli bacteremia and pyomyositis on the twelfth day of cefpirome therapy for neutropenic fever after chemotherapy due to acute myeloid leukemia. She recovered completely after a three-week course of meropenem and surgical excision. Pyomyositis should be included in the differential diagnosis when fever and muscular swelling develop in a patient with neutropenic status after chemotherapy. Early recognition of symptoms and proper diagnostic procedures are key to diagnosing pyomyositis. Both adequate antibiotics and surgical intervention are important for the successful treatment of pyomyositis caused by ESBL-producing E. coli.

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Bacteremia; beta-Lactamases; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Leukemia, Myeloid, Acute; Meropenem; Middle Aged; Pyomyositis; Thienamycins

Resistance profiles were compared among 18 extended-spectrum-beta-lactamase-producing (ESBL) and 27 acquired AmpC beta-lactamase-producing Escherichia coli isolates collected from Canadian intensive care units from 2005 to 2006. ESBL-producing E. coli isolates were more likely to be gentamicin resistant (P < 0.03), fluoroquinolone resistant (P < 0.0001), and multidrug resistant (P < 0.0001) than AmpC-producing E. coli isolates.

Topics: Bacterial Proteins; beta-Lactamases; Canada; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Gentamicins; Humans; Intensive Care Units; Microbial Sensitivity Tests

Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae have rapidly spread worldwide and pose a serious threat for health care-associated (HA) infection. We conducted molecular detection and characterization of ESBL-related bla genes, including bla(TEM), bla(SHV), bla(CTX-M), bla(VEB), bla(OXA), bla(PER), and bla(GES), among 362 isolates of ESBL-producing E. coli (n = 235) and ESBL-producing K. pneumoniae (n = 127) collected from patients who met the definition of HA infection at two major university hospitals in Thailand from December 2004 to May 2005. The prevalence of ESBL-producing E. coli and ESBL-producing K. pneumoniae, patient demographics and the susceptibilities of these bacteria to various antimicrobial agents were described. A total of 87.3% of isolates carried several bla genes. The prevalence of bla(CTX-M) was strikingly high: 99.6% for ESBL-producing E. coli (CTX-M-14, -15, -27, -40, and -55) and 99.2% for ESBL-producing K. pneumoniae (CTX-M-3, -14, -15, -27, and -55). ISEcp1 was found in the upstream region of bla(CTX-M) in most isolates. Up to 77.0% and 71.7% of ESBL-producing E. coli and ESBL-producing K. pneumoniae, respectively, carried bla(TEM); all of them encoded TEM-1. ESBL-producing K. pneumoniae carried bla(SHV) at 87.4% (SHV-1, -2a, -11, -12, -27, -71, and -75) but only at 3.8% for ESBL-producing E. coli (SHV-11 and -12). bla genes encoding VEB-1 and OXA-10 were found in both ESBL-producing E. coli (8.5% and 8.1%, respectively) and ESBL-producing K. pneumoniae (10.2% and 11.8%, respectively). None of the isolates were positive for bla(PER) and bla(GES). Pulsed-field gel electrophoresis analysis demonstrated that there was no major clonal relationship among these ESBL producers. This is the first study to report CTX-M-3, CTX-M-27, CTX-M-40, SHV-27, SHV-71, and SHV-75 in Thailand and to show that CTX-M ESBL is highly endemic in the country.

Topics: Adult; Bacterial Proteins; beta-Lactamases; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Endemic Diseases; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Polymerase Chain Reaction; Sequence Analysis, DNA; Thailand

Extended-spectrum-beta-lactamase (ESBL)-producing strains of Escherichia coli are a significant cause of bloodstream infections (BSI) in hospitalized and nonhospitalized patients. We previously showed that delaying effective antimicrobial therapy in BSI caused by ESBL producers significantly increases mortality. The aim of this retrospective 7-year analysis was to identify risk factors for inadequate initial antimicrobial therapy (IIAT) (i.e., empirical treatment based on a drug to which the isolate had displayed in vitro resistance) for inpatients with BSI caused by ESBL-producing E. coli. Of the 129 patients considered, 56 (43.4%) received IIAT for 48 to 120 h (mean, 72 h). Independent risk factors for IIAT include an unknown BSI source (odds ratios [OR], 4.86; 95% confidence interval [CI], 1.98 to 11.91; P = 0.001), isolate coresistance to >or=3 antimicrobials (OR, 3.73; 95% CI, 1.58 to 8.83; P = 0.003), hospitalization during the 12 months preceding BSI onset (OR, 3.33; 95% CI, 1.42 to 7.79; P = 0.005), and antimicrobial therapy during the 3 months preceding BSI onset (OR, 2.65; 95% CI, 1.11 to 6.29; P = 0.02). IIAT was the strongest risk factor for 21-day mortality and significantly increased the length of hospitalization after BSI onset. Our results underscore the need for a systematic approach to the management of patients with serious infections by ESBL-producing E. coli. Such an approach should be based on sound, updated knowledge of local infectious-disease epidemiology, detailed analysis of the patient's history with emphasis on recent contact with the health care system, and aggressive attempts to identify the infectious focus that has given rise to the BSI.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Multivariate Analysis; Risk Factors; Treatment Failure

We describe what we believe to be the first case of neonatal sepsis caused by CTX-M-producing Escherichia coli, in a low-weight preterm infant, born to a colonized mother who had received antibiotic treatment antepartum. Increased dissemination of extended-spectrum beta-lactamase-producing E. coli in the community should be borne in mind for empirical therapy of sepsis in high-risk newborns.

Topics: Anti-Bacterial Agents; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Infectious Disease Transmission, Vertical; Male; Meropenem; Pregnancy; Pregnancy Complications, Infectious; Sepsis; Thienamycins

A 25-year-old female was admitted to our intensive care unit with septic shock and multiorgan failure caused by extended-spectrum beta-lactamase-producing Escherichia coli originating from the right renal pelvis. A 16-day course of treatment with meropenem reversed the septic condition, but the infection recurred thereafter. The patient recovered fully after therapy was changed to tigecycline.

Topics: Adult; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Escherichia coli; Escherichia coli Infections; Female; Humans; Meropenem; Minocycline; Recurrence; Shock, Septic; Thienamycins; Tigecycline; Urinary Tract Infections

Among 144 ciprofloxacin-resistant Escherichia coli isolated in Brazil, one (0.69%) QnrA1-producing isolate was detected. The qnrA1 gene was associated with ISCR1. The QnrA1 determinant was carried on a 41-kb conjugative plasmid, which also carried a FOX-type cephalosporinase encoding gene and a class 1 integron with the aadB and catB3 cassettes. This is the first report of a qnrA-carrying isolate in a Latin American country.

Topics: Anti-Bacterial Agents; Ciprofloxacin; Conjugation, Genetic; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Integrons; Latin America; Molecular Sequence Data; Plasmids

The purpose of this study was to examine the in vivo efficacies of meropenem and ertapenem against extended-spectrum-beta-lactamase (ESBL)-producing isolates with a wide range of MICs. Human-simulated dosing regimens in mice were designed to approximate the free drug percent time above the MIC (fT>MIC) observed for humans following meropenem at 1 g every 8 h and ertapenem at 1 g every 24 h. An in vivo neutropenic mouse thigh infection model was used to examine the bactericidal effects against 31 clinical ESBL Escherichia coli and Klebsiella pneumoniae isolates and 2 non-ESBL isolates included for comparison at a standard 10(5) inoculum. Three isolates were examined at a high 10(7) inoculum as well. Meropenem displayed greater in vitro potency, with a median MIC (range) (microg/ml) of 0.125 (0.03 to 32), than did ertapenem, with 0.5 (0.012 to 128). Seven of the 31 ESBL isolates were removed from the efficacy analysis due to their inability to establish infection in the mouse model. When MICs wereMIC>or=23%) and meropenem (fT>MIC>or=75%). Ertapenem showed bacterial regrowth for seven of eight isolates, with MICs of>or=2 microg/ml (fT>MICMIC=30 to 65%). At a 10(7) inoculum, both agents eradicated bacteria due to adequate exposures (fT>MIC=20 to 45%). Due to low MICs, no difference in bacterial kill was noted for the majority of ESBL isolates tested. However, for isolates with raised ertapenem MICs of>or=2 microg/ml, meropenem displayed sustained efficacy due to its greater in vitro potency and higher resultant fT>MIC.

Topics: Animals; beta-Lactamases; beta-Lactams; Disease Models, Animal; Ertapenem; Escherichia coli; Escherichia coli Infections; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Mice; Microbial Sensitivity Tests; Thienamycins

Of the 181 unduplicated Escherichia coli strains isolated in nine different hospitals in three Portuguese regions, 119 were extended-spectrum beta-lactamase (ESBL)-CTX-M producers and were selected for phenotype and genotype characterization. CTX-M producer strains were prevalent among community-acquired infections (56%), urinary tract infections (76%), and patients >/=60 years old (76%). In MIC tests, all strains were resistant to cefotaxime, 92% were resistant to ceftazidime, 93% were resistant to quinolones, 89% were resistant to aminoglycoside, and 26% were resistant to trimethoprim-sulfamethoxazole; all strains were sensitive to carbapenems, and 92% of the strains had a multidrug resistance phenotype. Molecular methods identified 109 isolates harboring a bla(CTX-M-15) gene, 1 harboring the bla(CTX-M-32) gene (first identification in the country), and 9 harboring the bla(CTX-M-14) gene. All isolates presented the ISEcp1 element upstream from the bla(CTX-M) genes; one presented the IS903 element (downstream of bla(CTX-M-14) gene), and none had the IS26 element; 85% carried bla(TEM-1B), and 84% also carried a bla(OXA-30). Genetic relatedness analysis based on pulsed-field gel electrophoresis defined five clusters and indicated that 76% of all isolates (from cluster IV) corresponded to a single epidemic strain. Of the 47 strains from one hospital, 41 belonged to cluster IV and were disseminated in three main wards. CTX-M-producing E. coli strains are currently a problem in Portugal, with CTX-M-15 particularly common. This study suggests that the horizontal transfer of bla(CTX-M) genes, mediated by plasmids and/or mobile elements, contributes to the dissemination of CTX-M enzymes to community and hospital environments. The use of extended-spectrum cephalosporins, quinolones, and aminoglycosides is compromised, leaving carbapenems as the therapeutic option for severe infections caused by ESBL producers.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Microbial Sensitivity Tests; Middle Aged; Portugal

Topics: Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Conjugation, Genetic; Escherichia coli; Escherichia coli Infections; Humans; Male; Microbial Sensitivity Tests; Plasmids; Recombination, Genetic

Initial antibiotic treatment of severe infections can lead to clinical deterioration due to sudden endotoxin release and concomitant exaggerated inflammatory response. Antibiotic-induced morphological changes may contribute to this phenomenon. High-dose ceftazidime, which inhibits penicillin-binding protein (PBP)-1 in Gram-negative bacteria, causes quick bacteriolysis and low endotoxin release. Low-dose ceftazidime leads to PBP-3 inhibition, which causes bacterial filament formation, associated with high endotoxin releases. PBP-2-specific antibiotics induce spheroplasts, again associated with low endotoxin release. We hypothesized that antibiotic type, concentration and regimen influence bacterial morphology, endotoxin levels and inflammatory response.. Neutropenic mice with Escherichia coli or Pseudomonas aeruginosa sepsis were treated with ceftazidime or meropenem 10-320 mg/kg as an intravenous bolus or as continuous tail vein infusions of 0.1 mL/h. Four hours later, bacterial counts, morphology, plasma endotoxin, pro-inflammatory cytokines [tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)] and antibiotic concentrations were measured.. Continuous infusion of 80 mg/kg ceftazidime was the lowest dose preventing filaments in E. coli infections. Bolus treatment resulted in filament formation, irrespective of the dose. During continuous treatment, IL-6 and TNF-alpha concentrations were higher compared with bolus treatment and controls for both antibiotics and both strains. A clear relationship between cfu counts in muscle and circulating IL-6 was shown (r=- 0.579, P=0.007), suggesting that plasma IL-6 is a valuable indicator of bacterial killing at the infection site.. Our findings show that not PBP affinity but the method of antibiotic administration is crucial during initial treatment of severe infections.

Topics: Animals; Anti-Bacterial Agents; Ceftazidime; Colony Count, Microbial; Cytokines; Endotoxins; Escherichia coli; Escherichia coli Infections; Female; Meropenem; Mice; Penicillin-Binding Proteins; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Thienamycins

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Hospitals, Urban; Humans; India; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Sepsis; Thienamycins

Trimethoprim-sulfamethoxazole (TMP-SMX) is a combination chemotherapeutic agent, a commonly used antibiotic. Adverse drug reactions occur in 6-8% of patients. Although, the most common adverse reactions include mild gastrointestinal distress and cutaneous events, also a wide range of hematological abnormalities have been ascribed to TMP-SMX. We report a 40-year-old male patient who developed an early onset neutropenia, thrombocytopenia, generalised rash and oral candidiasis after 5 days long TMP-SMX therapy. Although generalised rash may seen more and improves with discontinuation of the therapy; severe neutropenia, thrombocytopenia and oral candidiasis are seen very rare and rarely leads to fatality as it was in our case. Despite thrombocyte transfusions, whole blood transfusions, red cell concentrates and filgrastim therapy we lost our patient. We want to underline that although the TMP-SMX combination is usually well tolerated it can also lead to fatal complications.

Topics: Adult; Anti-Infective Agents; Anti-Inflammatory Agents; Candidiasis, Oral; Cefepime; Cephalosporins; Chlorhexidine; Drug Eruptions; Escherichia coli; Escherichia coli Infections; Exanthema; Fatal Outcome; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Male; Meropenem; Neutropenia; Nystatin; Platelet Transfusion; Prednisolone; Recombinant Proteins; Thienamycins; Thrombocytopenia; Trimethoprim, Sulfamethoxazole Drug Combination

This study compared the in-vitro properties and in-vivo effects of Escherichia coli filaments, spheroplasts and normal cells in a murine thigh infection model. E. coli was exposed to ceftazidime, meropenem or saline to obtain filaments, spheroplasts or normal bacilli, which were then injected into neutropenic mice. After 24 h, morphology, CFUs, local and circulating endotoxin levels, cytokine levels and mortality were recorded, and correlations between bacterial and host parameters of infection were investigated. Filaments and spheroplasts contained more endotoxin/CFU than controls. Histological studies showed that morphologically altered bacteria changed into rod-shaped cells in the absence of antibiotics. Bacterial spread to the liver was significantly higher in mice challenged with rod-shaped cells, compared with antibiotic-exposed bacteria (p 0.007). Muscle endotoxin levels correlated significantly with circulating interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, and both pro-inflammatory cytokines were correlated significantly (p 0.011). Despite a tendency toward higher local and systemic concentrations of endotoxin in the filament group, inflammatory responses and survival did not differ between groups. It was concluded that morphologically altered bacteria contain more endotoxin and can regain a rod shape after withdrawal of antibiotics, while non-antibiotic-exposed bacteria show greater spread to the liver. There was a clear intra-individual relationship between local endotoxin, systemic endotoxin, TNF-alpha and IL-6 production, but these parameters did not differ among groups.

Topics: Animals; Animals, Outbred Strains; Anti-Bacterial Agents; Ceftazidime; Cyclophosphamide; Cytoskeleton; Disease Models, Animal; Endotoxins; Escherichia coli; Escherichia coli Infections; Female; Interleukin-6; Liver; Meropenem; Mice; Muscles; Muscular Diseases; Neutropenia; Spheroplasts; Thienamycins; Thigh; Tumor Necrosis Factor-alpha

A 76-year-old woman had recurrent urosepsis due to extended-spectrum beta -lactamase-positive Escherichia coli. Imipenem resistance was detected after long-term imipenem-meropenem therapy. The carbapenem-hydrolyzing enzyme gene was identified as blaKPC-3. To our knowledge, this is the first documented case in which carbapenem-resistant E. coli emerged during therapy with imipenem and meropenem, and the first identification of the carbapenem-hydrolyzing enzyme in E. coli isolates.

Topics: Aged; Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Meropenem; Microbial Sensitivity Tests; Thienamycins; Urinary Tract Infections

Topics: Brain Abscess; Drug Administration Schedule; Drug Resistance, Bacterial; Escherichia coli Infections; Humans; Infant, Newborn; Klebsiella Infections; Meningitis, Bacterial; Meropenem; Sepsis; Thienamycins; Treatment Outcome

Neonatal Escherichia coli meningitis is a serious disease with high mortality and poor outcome. Ventriculitis, brain abscess and subdural empyema are frequent, with no homogeneous recommendations available for these complications. The case of a newborn infant who developed sepsis and meningitis caused by E. coli is presented. During intravenous treatment with ampicillin, cefotaxime and gentamycin in recommended doses, the patient developed severe subdural abscesses detected on MRI. After consequent antibiotic therapy over 2 months with fosfomycin, amikacin and meropenem the patient improved clinically and the abscesses regressed and disappeared without neurosurgical intervention. At the age of 6.5 months the infant is healthy and well developed. The conservative treatment of subdural abscesses complicating neonatal Escherichia coli meningitis without neurosurgical intervention is possible. The treatment of the individual case should be discussed between pediatrician and neurosurgeon.

Topics: Amikacin; Brain; Drug Therapy, Combination; Echoencephalography; Empyema, Subdural; Escherichia coli Infections; Female; Fosfomycin; Humans; Infant, Newborn; Intensive Care, Neonatal; Magnetic Resonance Imaging; Meningitis, Escherichia coli; Meropenem; Microbial Sensitivity Tests; Patient Care Team; Thienamycins; Treatment Outcome

The bactericidal effect of some antibiotic and antineoplastic agents commonly used in clinical practice was investigated to analyse whether the combinations act synergistically, have indifferent or antagonistic antibacterial effects compared to the effect of the antibiotics alone.. The rate of killing of meropenem, ceftazidime and tobramycin was studied against six different strains of Staphylococcus aureus and Escherichia coli, and the results were compared to the rate of killing of the antibiotics in combination with the cytostatic drugs doxorubicin, etoposide and 5-fluorouracil (5-FU).. Tobramycin showed synergy against two strains of S. aureus after 3 h in the presence of 5-FU and against one strain of S. aureus in the presence of doxorubicin. Meropenem induced an antagonistic bactericidal effect against one isolate of S. aureus after 24 h. Ceftazidime expressed an indifferent bactericidal effect together with the cytostatic agents. The antineoplastic agents had no impact on the bacterial killing of any of the antibiotics against E. coli.. Tobramycin expressed a significantly better bactericidal effect against S. aureus after 3 h in the presence of doxorubicin and 5-FU than tobramycin alone. Meropenem expressed antagonism against one clinical strain of S. aureus, but the cytostatic drugs did not affect the killing of other strains tested. Ceftazidime expressed indifferent bactericidal activity together with the antineoplastic agents.

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Ceftazidime; Cephalosporins; Doxorubicin; Drug Interactions; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Etoposide; Fluorouracil; Meropenem; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus aureus; Thienamycins; Tobramycin

The 2alpha-functionalized 1beta-methylcarbapenems 3 were synthesized from the 2-formyl 1beta-methylcarbapenem intermediate 5. The best compound in the series of 2alpha-(hydroxy)alkylcarbapenems, KR-21012, displayed well balanced in vitro and in vivo activity as a parent compound of oral carbapenem.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Carbapenems; Drug Stability; Escherichia coli Infections; Gram-Negative Bacteria; Gram-Positive Bacteria; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Streptococcal Infections; Structure-Activity Relationship; Survival Rate

Meropenem and comparator antibiotics, including ceftriaxone, ceftazidime, benzyl penicillin and a combination of ampicillin plus gentamicin, were evaluated in a model of bacterial meningitis in the guinea-pig. The model is an acute infection in which challenge with each organism, if untreated, causes an increase in numbers of white blood cells, elevation of protein concentrations and 6-8 log10 cfu/mL of bacteria in the CSF. Infections caused by Haemophilus influenzae, Neisseria meningitidis, three strains of Streptococcus pneumoniae (two penicillin-resistant), Escherichia coli, Pseudomonas aeruginosa and Listeria monocytogenes all responded to meropenem, which was as active as the comparator agents in all studies, and was more active in most. Of particular note were the results seen against S. pneumoniae (penicillin-resistant) infections, in which meropenem was significantly more effective than ceftriaxone. Also notable were results from the P. aeruginosa infection where meropenem, at low doses, was more effective than ceftazidime. Activity against L. monocytogenes was equivalent to that produced by treatment with the combination of ampicillin plus gentamicin, even when treatment was delayed. These results show that, in an animal model, meropenem penetrates into CSF in concentrations sufficient to produce significant reductions in the numbers of common and less common pathogens.

Topics: Ampicillin; Animals; Carbapenems; Ceftazidime; Ceftriaxone; Cephalosporins; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Drug Evaluation; Drug Resistance, Microbial; Escherichia coli Infections; Gentamicins; Guinea Pigs; Haemophilus Infections; Haemophilus influenzae; Listeriosis; Meningitis, Bacterial; Meropenem; Neisseria meningitidis; Penicillin G; Pneumococcal Infections; Thienamycins

Several pharmacodynamic parameters are being studied and applied to the design of dosage regimens. The thigh infection model in neutropenic mice has been used in this study to investigate the in vivo postantibiotic effect (PAE) of meropenem against S. aureus, E. coli and P. aeruginosa. The sub-minimum inhibitory concentration (sub-MIC) postantibiotic effect (PA SME) of 1/2, 1/4 and 1/8 x MIC was also determined in vitro on S. aureus and E. coli after pre-exposure of these microorganisms to 10 x MIC of meropenem. The in vitro PAE was also determined. In vivo killing curves using 2 different short dosage regimens were also studied to relate the lethal effect to the time that serum levels were above the MIC. No significant in vivo and in vitro PAEs were observed. The PA SMEs were higher for S. aureus than for E. coli. The 2 short dosage regimens, in vivo, were equally effective in killing S. aureus, but not E. coli. These results suggest that the pharmacodynamics of meropenem on Gram-negative strains may need further study to elucidate the mechanisms and characteristics of these parameters. On the other hand, we need to standardize a reliable in vitro method to monitor regrowth with a good correlation with the in vivo conditions.

Topics: Animals; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Escherichia coli; Escherichia coli Infections; Female; In Vitro Techniques; Meropenem; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections; Staphylococcus aureus; Thienamycins

In a rabbit Escherichia coli meningitis model, endotoxin liberation and concentrations of leukocytes, tumor necrosis factor (TNF), and lactate were compared after a single intravenous dose of cefotaxime, cefpirome, meropenem, chloramphenicol, or gentamicin. These antibiotics caused a 2- to 10-fold increase in cerebrospinal fluid concentrations of free (filterable) endotoxin within 2 h of starting treatment. By contrast, free endotoxin concentrations increased almost 100-fold in untreated animals 4 h later as bacteria continued to multiply. An initial enhancement of inflammation in the central nervous system occurred in all treatment groups compared with untreated controls. No significant differences were observed between treatment groups except for lower TNF concentrations in chloramphenicol-treated animals. Antibiotic therapy in E. coli meningitis, irrespective of the agent used, may result in an increase in free endotoxin and enhancement of inflammation, but the amount of endotoxin liberated is considerably smaller than that shed by untreated bacteria.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Cefpirome; Cephalosporins; Chloramphenicol; Endotoxins; Escherichia coli Infections; Gentamicins; Inflammation; Male; Meningitis, Bacterial; Meropenem; Rabbits; Thienamycins

Forty-five children were treated with meropenem (MEPM) and the clinical efficacy and side effects were evaluated. The ages of the patients ranged from 1 month to 9 years and their body weights from 5.2 to 25 kg. Doses given were 17.2-45.5 mg/kg every 6 to 8 hours for 2 to 24.5 days. Those patients who responded to the MEPM treatment included 15 children with pneumonia, 7 with pharyngitis, 3 with cervical lymphadenitis, 3 with cellulitis, 10 with urinary tract infections and 4 with other infections. Among 42 children, the results were excellent in 29, good in 12 and fair in 1. The drug was well tolerated, although slightly elevated serum concentrations of transaminases occurred in 5 patients, eosinophilia in 2 patients, and neutropenia in 1 patient among 45 patients examined. The pharmacokinetic studies on MEPM were done in 6 patients. Their ages ranged from 2 to 9 years and body weights from 14.5 to 23.2 kg. In 4 patients, plasma concentrations at the end of 30 minutes drip infusion of 20 mg/kg were 29.28 +/- 10.29 micrograms/ml and those 3 hours later were 0.49 +/- 0.26 micrograms/ml. Serum elimination half-lives of the drug were 0.66 +/- 0.12 hours in these patients. Excretion rates of this drug into urine in the first 6 hours after initiation of drug administration were 53 and 40% in 2 of these patients. In 2 patients with 35 and 44 mg/kg of drug administration, plasma concentrations were higher than those given 20 mg/kg of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bacterial Infections; Bifidobacterium; Child; Child, Preschool; Enterobacteriaceae; Escherichia coli Infections; Feces; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Meropenem; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes; Thienamycins

Bacteriological and clinical studies have been performed on meropenem (MEPM, SM-7338), a newly developed carbapenem antibiotic, in the pediatric field. 1. Antibacterial activities of MEPM against 24 clinical isolates were determined. MEPM showed excellent activity against Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria, especially Escherichia coli and Branhamella catarrhalis. Against Haemophilus influenzae, MEPM had a higher activity than imipenem and flomoxef, but had a lower activity than piperacillin and cefoperazone. 2. Clinical efficacies of MEPM were evaluated in 32 cases with bacterial infections. A poor efficacy was observed in 1 patient with phlegmon but excellent or good efficacies were obtained in other 31 patients with tonsillitis (1), pneumonia (17), UTI (12), or SSSS (1). The overall efficacy rate was 96.9%. All strains except 1 of S. aureus were eradicated by the administration of MEPM, and a high eradication rate of 95.8% (23 out of 24 strains) was obtained. 3. No side effects were observed in 35 evaluated cases. As abnormal laboratory test results, elevated GOT, elevated GPT, eosinophilia and neutropenia were noted in 4, 4, 4 and 2 patients, respectively. 4. Influences on blood coagulation parameters were studied. PIVKA II was elevated upon administration of MEPM in some cases, but no changes in ATT, TT, HPT or Fbg were observed during the treatment. Based on the above results, it has been concluded that MEPM is a safe and effective drug to use in the treatment of pediatric infections. The usual recommended dosage and administration should be 10 to 20 mg/kg of MEPM at a time, using intravenous drip infusion, 3 times a day.

Topics: Adolescent; Bacterial Infections; Child; Child, Preschool; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Infant; Male; Meropenem; Moraxella catarrhalis; Neisseriaceae Infections; Pneumococcal Infections; Staphylococcal Infections; Streptococcal Infections; Streptococcus pyogenes; Thienamycins

Meropenem and comparative antibiotics were evaluated in five models of infection. All antibiotics were administered parenterally; imipenem was used in combination with cilastatin but meropenem and other agents were given alone. Generalized infections in mice caused by Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Serratia marcescens, Proteus mirabilis or Pseudomonas aeruginosa all responded to low doses of meropenem or imipenem. Immunocompromised mice infected with Ps. aeruginosa responded to slightly higher doses of meropenem or gentamicin but required four to seven times the dose of other agents. Those given a greater challenge of Ps. aeruginosa were treated most successfully by meropenem. Treatment with meropenem, imipenem or ceftazidime caused significant reductions of E. coli in the urinary bladder and kidneys of mice challenged per urethram. Infection with Ps. (Xanthomonas) maltophilia localized to the subcutaneous neck tissue of guinea pigs was also treated successfully. Lung infections caused by Ps. aeruginosa in guinea pigs were treated effectively by meropenem, imipenem, and ceftazidime at the dose of 10 mg/kg but only meropenem eradicated bacteria from all the tissues examined. These results demonstrate that meropenem has excellent antibacterial activity in vivo in both normal and immunocompromised animals and in some models of infection is superior to imipenem.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Carbapenems; Escherichia coli Infections; Guinea Pigs; Immunosuppression Therapy; Lung Diseases; Male; Meropenem; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests; Pseudomonas Infections; Respiratory Tract Infections; Thienamycins; Urinary Tract Infections