ro13-9904 and Escherichia-coli-Infections

Transrectal ultrasound guided biopsy (TRUSB) of the prostate directly contaminates the prostate with rectal flora. Patients commonly receive fluoroquinolone (FQ) antibiotics to prevent infection. Infectious complications following TRUSB are increasing. The most common offending organism is Escherichia coli (E. coli), with isolates of this bacteria showing growing resistance to FQs. We present to our knowledge the first reported case of seminal vesicle abscess formation after TRUSB. The abscess was initially not seen on computed tomography and eventually treated with percutaneous drainage by a transgluteal approach. We review literature on infectious complications following TRUSB with implications for future antibiotic prophylaxis.

Topics: Abscess; Aged; Anti-Bacterial Agents; Buttocks; Ceftriaxone; Drainage; Escherichia coli; Escherichia coli Infections; Humans; Image-Guided Biopsy; Levofloxacin; Male; Nitrofurantoin; Prostate; Seminal Vesicles; Treatment Outcome; Ultrasound, High-Intensity Focused, Transrectal

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

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

To confirm whether oral antibiotic treatment is as efficacious as sequential intravenous/oral antibiotic treatment in the prevention of renal scarring in children with acute pyelonephritis and scintigraphy-documented acute lesions.. In a prospective multicenter trial, children aged 1 to 36 months with their first case of acute pyelonephritis, a serum procalcitonin concentration ≥0.5 ng/mL, no known uropathy, and a normal ultrasound exam were randomized into 2 treatment groups. They received either oral cefixime for 10 days or intravenous ceftriaxone for 4 days followed by oral cefixime for 6 days. Patients with acute renal lesions detected on early dimercaptosuccinic acid scintigraphy underwent a follow-up scintigraphy 6 to 8 months later.. The study included 171 infants and children. There were no significant differences between the 2 groups in any clinical characteristic. Initial scintigraphy results were abnormal for 119 children. Ninety-six children were measured for renal scarring at the follow-up scintigraphy (per protocol analysis population). The incidence of renal scarring was 30.8% in the oral treatment group and 27.3% for children who received the sequential treatment.. Although this trial does not statistically demonstrate the noninferiority of oral treatment compared with the sequential treatment, our study confirmed the results of previously published reports and therefore supports the use of an oral antibiotic treatment of primary episodes of acute pyelonephritis in infants and young children.

Topics: Acute Disease; Administration, Oral; Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Cefixime; Ceftriaxone; Child, Preschool; Drug Administration Schedule; Escherichia coli Infections; Female; Humans; Infant; Infusions, Intravenous; Male; Prospective Studies; Protein Precursors; Pyelonephritis; Radionuclide Imaging

The efficacy of ertapenem, 1 g once a day, for treatment of adults with serious infections caused by Enterobacteriaceae was compared with ceftriaxone 1 g once a day [complicated urinary tract infection (CUTI) and community-acquired pneumonia (CAP)] or piperacillin-tazobactam, 3.375 g every 6 h (complicated intra-abdominal, complicated skin/skin structure and acute pelvic infections).. This combined analysis included the subgroup of all 1167 treated patients infected with Enterobacteriaceae from seven randomized double-blind studies.. Escherichia coli was the most common pathogen, accounting for 65.3% of all Enterobacteriaceae. Among evaluable patients with deep tissue (intra-abdominal, skin and pelvic) infections, the combined clinical cure rates were 84.8% (223 of 263) for ertapenem and 82.9% (194 of 234) for piperacillin-tazobactam [95% confidence interval (CI) for the difference, adjusting for infection, -4.9% to 8.9%]. Cure rates by infection for ertapenem and piperacillin-tazobactam, respectively, were: intra-abdominal, 85.1% (143 of 168) and 79.9% (119 of 149); pelvic, 86.8% (46 of 53) and 94% (47 of 50); skin/skin structure, 81% (34 of 42) and 80% (28 of 35). Among patients with CUTI, microbiological cure rates were 90.5% (220 of 243) for ertapenem and 92% (196 of 213) for ceftriaxone (95% CI for the difference, -7.1% to 4.1%). In patients with CAP, clinical cure rates were 95% (19 of 20) for ertapenem and 88.9% (16 of 18) for ceftriaxone.. Ertapenem therapy was as effective as either piperacillin-tazobactam or ceftriaxone for serious infections caused by Enterobacteriaceae.

Topics: Adult; Aged; beta-Lactams; Ceftriaxone; Cephalosporins; Community-Acquired Infections; Double-Blind Method; Drug Therapy, Combination; Enterobacteriaceae Infections; Ertapenem; Escherichia coli Infections; Humans; Lactams; Middle Aged; Multicenter Studies as Topic; Penicillanic Acid; Piperacillin; Tazobactam; Treatment Outcome; Urinary Tract Infections

The aim of this study was to determine whether a short course of ceftriaxone was sufficient to cure spontaneous bacterial peritonitis (SBP) in cirrhotic patients.. We studied 33 cirrhotic patients with SBP. All of them were treated with ceftriaxone, 1.0 g IV, every 12 h for 5 days. Twenty-one variables were recorded to evaluate their relationship to the resolution of SBP.. The mean age of the patients was 45 years. Twenty-three were males and 10 females. The etiology of cirrhosis was alcoholic in 42% of the patients, and 82% of the patients belonged to Child-Pugh Class C. Hepatic encephalopathy was present in 39% of the patients. The most frequent organism causing SBP was Escherichia coli (60%). Resolution of SBP on day 5 of treatment was achieved in 73% of the patients. Total resolution of SBP after prolonged therapy with ceftriaxone or another agent. selected according to antibiotic susceptibility, was achieved in 94% of the patients. Hospital mortality was 12%. Multivariate analysis showed no factor that was significantly related to the resolution of SBP, but univariate analysis showed that renal impairment and positive culture tended to be related.. A short course (5 days) of ceftriaxone is useful therapy for SBP. If the polymorphonuclear differential count in ascitic fluid is less than 250 cells/mm3 on day 5 of treatment, the antibiotic can be discontinued.

Topics: Adolescent; Adult; Aged; Ceftriaxone; Cephalosporins; Drug Administration Schedule; Escherichia coli; Escherichia coli Infections; Female; Hospital Mortality; Humans; Liver Cirrhosis; Logistic Models; Male; Middle Aged; Peritonitis

To compare the efficacy and safety of ertapenem, a new once-daily parenteral beta-lactam, with that of ceftriaxone for the initial empiric treatment of adults with complicated urinary tract infections (cUTIs).. In a multicenter, prospective, double-blind study, patients with cUTIs were stratified as to whether they had acute pyelonephritis or other cUTIs (without pyelonephritis) and randomized to receive ertapenem, 1 g once a day, or ceftriaxone, 1 g once a day. After 3 days, patients with a satisfactory clinical response could be switched to an oral antimicrobial agent.. Of 258 randomized patients, 97 (55.4%) in the ertapenem group and 53 (63.9%) in the ceftriaxone group were evaluated microbiologically. Almost all patients in each treatment group were switched to oral therapy. The mean duration of therapy was similar in both treatment groups: parenteral, approximately 4 days; total, approximately 13 days. The most common pathogen was Escherichia coli. At the primary efficacy endpoint, 5 to 9 days after treatment, 85.6% of patients who received ertapenem and 84.9% who received ceftriaxone had a favorable microbiologic response, indicating that the two treatment groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups.. In this study, ertapenem was as effective as ceftriaxone for the initial treatment of cUTI in adults, was generally well tolerated, and had a similar safety profile.

Topics: Administration, Oral; Adult; Age Factors; Anti-Bacterial Agents; beta-Lactams; Ceftriaxone; Cephalosporins; Double-Blind Method; Ertapenem; Escherichia coli; Escherichia coli Infections; Humans; Infusions, Intravenous; Lactams; Prospective Studies; Treatment Outcome; Urinary Tract Infections

The combination of penicillin with an aminoglycoside has been recommended as an initial treatment of choice for patients with acute infections of the biliary tract. However, many patients have incidence of renal problems and for this reason aminoglycosides must be avoided. Newer antimicrobial agents with lesser nephrotoxic effects will be tried. We, therefore, performed a prospective, randomized trial of ofloxacin, a new quinolone and ceftriaxone in patients with acute biliary tract infections. Fifty-two patients with severe biliary tract infections (cholecystitis and cholangitis) were randomly assigned to receive either ofloxacin (n = 28) or ceftriaxone (n = 24). The 2 groups receiving antibiotics were similar with respect to all clinical and laboratory parameters. Bacteria were documented in 48% of patients in the ofloxacin group and in 46% in the ceftriaxone group. The percentage of patients with a clinical cure or significant improvement was the same in the 2 groups. No significant difference was noted between the 2 treatment groups with respect to drug toxicity. These data suggest that intravenous ofloxacin followed by oral administration is an effective and safe single drug for the therapy of patients with acute biliary tract infections.

Topics: Anti-Infective Agents; Bacteremia; Ceftriaxone; Cephalosporins; Cholangitis; Cholecystitis; Escherichia coli Infections; Female; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Ofloxacin; Phlebitis

The disposition of ornidazole and its two major hydroxylated metabolites was studied in five pregnant women (gestational ages 25 5/7 to 38 4/7 weeks) with either chorioamnionitis or pyelonephritis treated with ceftriaxone 2 g, tobramycin 3 mg/kg body weight and ornidazole 1 g all administered once-daily. Two series of blood samples were obtained, the first on the first day of treatment and the second at steady-state on day 5. Local and systemic tolerability of ornidazole was excellent and patients showed complete remission without premature delivery. There was no evidence of ornidazole accumulation, and the pharmacokinetic parameters were very similar to those seen in healthy subjects. The dosage regimen of ornidazole therefore requires no adjustment during pregnancy. Trough concentrations of ornidazole measured at 24 h post dose were above the MIC of sensitive organisms. Children born to the trial patients showed normal initial development and their growth was normal.

Topics: Adult; Ceftriaxone; Chorioamnionitis; Drug Therapy, Combination; Escherichia coli Infections; Female; Humans; Infant, Newborn; Ornidazole; Pregnancy; Pregnancy Complications, Infectious; Proteus Infections; Pyelonephritis; Tobramycin

A prospective, randomized clinical trial was conducted to compare the efficacy and tolerance of a single dose of 1 g ceftriaxone i.v. daily with 3 doses of 1 g cefotaxime i.v. daily for obstetric and gynecologic infections. Both agents are characterized by a wide spectrum and potent activity. Furthermore, ceftriaxone has an outstanding serum half-life of 8 h. 41 patients with pelvic inflammatory disease, pelvic or wound infections after vaginal or abdominal hysterectomy, endomyometritis and urinary-tract infection were included. Patients were monitored clinically by routine laboratory methods (erythrocyte sedimentation rate, white blood cell count and cross-reacting protein) and bacteriologically. Clinical parameters of infection were fever, local pain and/or tenderness, a sactosalpinx or pyosalpinx at palpation and cervical secretion. Clinical cure was achieved in 77.3% in the ceftriaxone and in 78.9% in the cefotaxime group, improvement in 3 (13.6%) and 4 patients (21.0%), respectively. 2 clinical failures were seen in the ceftriaxone group. One was a severe pelvic infection following vaginal hysterectomy, which responded to the addition of metronidazole, the other was due to a chlamydial salpingitis, which was cured with a 10-day course of doxycycline. Both antibiotics were well tolerated. Our results suggest that for obstetric and gynecologic infections a single 1-gram dose of ceftriaxone is equally effective as three 1-gram doses of cefotaxime.

Topics: Cefotaxime; Ceftriaxone; Endometritis; Escherichia coli Infections; Female; Humans; Hysterectomy; Pelvic Inflammatory Disease; Prospective Studies; Randomized Controlled Trials as Topic; Surgical Wound Infection

In a prospective study 105 children hospitalized with soft tissue infection, 11 children with suppurative arthritis and 9 children with osteomyelitis were treated with either parenterally administered ampicillin/sulbactam or ceftriaxone. Treatment was randomized using a computer-generated table in a 2:1 fashion: 84 patients received ampicillin/sulbactam and 41 patients received ceftriaxone. Organisms isolated from wound site or blood cultures included Staphylococcus aureus (33), Streptococcus pyogenes (19), Haemophilus influenzae (9) including 4 beta-lactamase-positive organisms, Streptococcus pneumoniae (5), Neisseria gonorrhoeae (3) and 9 other organisms. Clinical and bacteriologic response was satisfactory in 100% of the ampicillin/sulbactam-treated patients and in 93% of the ceftriaxone-treated patients. Two patients with S. aureus infections treated with ceftriaxone had a delayed response and required change in therapy to parenterally administered oxacillin. Ampicillin/sulbactam represents a potentially useful single agent for the treatment of cellulitis and bone or joint infections in pediatric patients.

Topics: Acinetobacter Infections; Adolescent; Ampicillin; Arthritis, Infectious; Ceftriaxone; Cellulitis; Child; Child, Preschool; Drug Therapy, Combination; Escherichia coli Infections; Female; Gonorrhea; Haemophilus Infections; Humans; Infant; Male; Osteomyelitis; Prospective Studies; Random Allocation; Staphylococcal Infections; Streptococcal Infections; Sulbactam

70 children aged 4 months-12 years, with bacteriologically proven bacterial meningitis were treated with either intramuscular (IM) ceftriaxone (CFT) 100 mg/kg given once daily, or with combined IM ampicillin 160 mg/kg/day and IM chloramphenicol 100 mg/kg/day (AMC) given every 6 h. There were 35 children in each of the treatment groups. The children in both groups were comparable with regard to age, sex, duration of illness, and state of consciousness. 29 children in the CFT group and 26 in the AMC group recovered without any permanent complications or sequelae. Of the 15 children who died 10 (3 in the CFT and 7 in the AMC group) were in deep coma when treatment was started. Intramuscular CFT given once daily proved effective and much easier to administer than our standard hospital therapy with combined AMC given every 6 h IM.

Topics: Ampicillin; Ceftriaxone; Child; Child, Preschool; Chloramphenicol; Drug Therapy, Combination; Escherichia coli Infections; Female; Humans; Infant; Injections, Intramuscular; Male; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Time Factors

Single-dose antibiotic therapy for urinary tract infections in which no underlying structural or neurologic lesions are present holds the promise of greater patient compliance and convenience. We present the results of a study comparing a single intramuscular dose of a long-acting, third-generation cephalosporin, ceftriaxone, with a standard, five-day regimen of trimethoprim-sulfamethoxazole (TMS). Fifty-two patients were entered into the study. After randomization, 26 were assigned to the TMS group and 26 were assigned to the ceftriaxone group. Of the patients who completed the study, 13 of the TMS group had positive cultures at the time of initial presentation, and 20 of the ceftriaxone group had positive cultures. There was no statistical difference between the groups in symptoms of dysuria, hematuria, frequency, flank pain, and nocturia (alpha = .05). The physical parameters of age, blood pressure, pulse, and temperature were similar in the two groups (alpha = .05), as were the types of infecting organisms (alpha = .05). When comparing the two regimens, the ceftriaxone group cure rate (18 of 20, 90%) was not found to be significantly different from that of the TMS-treated control group (13 of 13) (alpha = .05).

Topics: Administration, Oral; Cefotaxime; Ceftriaxone; Drug Combinations; Drug Evaluation; Escherichia coli Infections; Female; Humans; Injections, Intramuscular; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

Seventy-seven patients with acute bacterial infections were treated with ceftriaxone (1 gm administered intravenously every 12 hours). The 58 patients evaluable for efficacy had 60 infections, including 39 of the respiratory tract, 14 of the urinary tract, and seven of soft tissue. Five patients were bacteremic. The mean duration of ceftriaxone treatment was eight days for patients with respiratory and urinary tract infections and 13 days for patients with other types of infections. A satisfactory clinical response occurred in 56 (93%) of the infections. Eighty-four (94%) of the 89 pretherapy pathogens were bacteriologically eradicated. Included were all 19 isolates of Haemophilus influenzae, all 15 of Streptococcus pneumoniae, all 12 of Escherichia coli, 22 of the 23 isolates of other Enterobacteriaceae species, three of five isolates of Pseudomonas aeruginosa, and three of four isolates of Staphylococcus aureus. Two cases of superinfection (one with bacteremia) occurred with P aeruginosa. There were two cases each of reinfection and colonization with Streptococcus faecalis. One patient developed manifestations of culture-documented S pneumoniae meningitis eight hours after the first dose was administered. Peak and trough plasma levels of ceftriaxone were 142 and 64 micrograms/ml. Ceftriaxone achieved therapeutic levels in infected cerebrospinal fluid and in the abscess fluid of selected patients. Adverse effects, which were mild, included diarrhea in 4% of the patients and elevated transaminase levels in 10%.

Topics: Adult; Aged; Alanine Transaminase; Bacterial Infections; Cefotaxime; Ceftriaxone; Clinical Trials as Topic; Connective Tissue Diseases; Diarrhea; Escherichia coli Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Middle Aged; Pneumococcal Infections; Respiratory Tract Infections; Sepsis; Streptococcus pneumoniae; Time Factors; Urinary Tract Infections

In two studies, the therapeutic effect of a single intramuscular dose of Ro 13-9904 (Rocephin) of 500 or 250 mg, respectively, was compared with a single intramuscular dose of 80 mg tobramycin in chronic urinary tract infections. 7 days after 500 mg Ro 13-9904, the infections were eradicated in 10 of the 11 patients; 7 days after 250 mg Ro 13-9904, 4 of 11 patients were reinfected with selected resistant Streptococcus faecalis. After tobramycin, 9 of 23 patients were cured. Considering enterococci as dangerous organisms in several respects we recommend a single dose of 500 mg Ro 13-9904 with a satisfactory local tolerance. Tobramycin is unsuitable for single-dose treatment.

Topics: Aged; Bacterial Infections; Ceftriaxone; Cephalosporins; Clinical Trials as Topic; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Tobramycin; Urinary Tract Infections

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

Children who have been discharged from hospital in sub-Saharan Africa remain at substantial risk of mortality in the post-discharge period. Antimicrobial resistance (AMR) may be an important factor. We sought to determine the prevalence and risk factors associated with AMR in commensal Escherichia coli (E. coli) from Kenyan children at the time of discharge.. Fecal samples were collected from 406 children aged 1-59 months in western Kenya at the time of discharge from hospital and cultured for E. coli. Susceptibility to ampicillin, ceftriaxone, cefotaxime, ceftazidime, cefoxitin, imipenem, ciprofloxacin, gentamicin, combined amoxicillin/clavulanic acid, trimethoprim-sulfamethoxazole, azithromycin, and chloramphenicol was determined by disc diffusion according to guidelines from the Clinical and Laboratory Standards Institute (CLSI). Poisson regression was used to determine associations between participant characteristics and the presence of extended-spectrum beta-lactamases (ESBL) producing E. coli. Non-susceptibility to ampicillin (95%), gentamicin (44%), ceftriaxone (46%), and the presence of ESBL (44%) was high. Receipt of antibiotics during the hospitalization was associated with the presence of ESBL (aPR = 2.23; 95% CI: 1.29-3.83) as was being hospitalized within the prior year (aPR = 1.32 [1.07-1.69]). Open defecation (aPR = 2.02; 95% CI: 1.39-2.94), having a toilet shared with other households (aPR = 1.49; 95% CI: 1.17-1.89), and being female (aPR = 1.42; 95% CI: 1.15-1.76) were associated with carriage of ESBL E. coli.. AMR is common among isolates of E. coli from children at hospital discharge in Kenya, including nearly half having detectable ESBL.

Topics: Aftercare; Ampicillin; Anti-Bacterial Agents; beta-Lactamases; Ceftriaxone; Child; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Gentamicins; Hospitals; Humans; Kenya; Male; Microbial Sensitivity Tests; Patient Discharge

The capacity of antibiotics to modulate bacterial virulence has raised concerns over the appropriateness of antibiotic therapies, including when dosing strategies fall below sub-therapeutic levels. In this work, we investigated the ability of antibiotics to influence virulence in Escherichia coli isolated from urinary tract infection (UTI).. Out of 120 isolates, 32.5% carried pap, 21.7% carried hlyA, and 17.5% carried cnf. The predominant B2 phylogroup was significantly associated with the quinolone-resistant isolates. A significant association was seen between the presence of hlyA hemolysin and susceptibility to ceftriaxone and ciprofloxacin (P < 0.05). Sub-inhibitory concentrations of both antibiotics reduced the levels of hlyA expression and hemolysis in isolates treated with antibiotics compared to untreated isolates (P < 0.05). Growth rate assay showed that the decrease in hlyA expression was not an effect of decreased growth rate.. Our study indicated the inhibitory effect of ciprofloxacin and ceftriaxone on the level of hemolysis, suggesting that the sub-inhibitory concentrations of these antibiotics may affect the outcome of infections. Further studies, including animal models may elucidate the outcome of virulence modulation by these antibiotics in UTI pathogenesis.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Ciprofloxacin; Escherichia coli; Escherichia coli Infections; Hemolysis; Urinary Tract Infections; Virulence; Virulence Factors

Urinary tract infections (UTIs) and bacterial resistance to antibiotics is global health problem and a threat to public health in many countries.. The study aimed to determine the prevalence of MDR Escherichia coli and Klebsiella pneumoniae in UTI patients.. The midstream urine samples of 120 patients were collected and cultured as described by the protocols at the respective sample collection sites on MacConkey Blood agar. Samples were tested by using the fully automated VITEK 2 Compact system for Gram-negative identification and detection of antimicrobial susceptibility of microorganisms.. The most prevalent pathogen was E. coli, which was found in 82 (68.3%) urine samples, followed by K. pneumonia, found in 38 (31.7%) urine samples. As far as antibiotic resistance is concerned, E. coli isolates were found to be highly resistant for ceftriaxone (89.0% of the isolates), ampicillin (86.6%), levofloxacin (82.9%), cefotaxime (79.3%), aztreonam (74.4%), ceftazidime (68.3%) and gentamicin, piperacillin, and trimethoprim-sulfamethoxazole, 54.9 and 53.7%, respectively. The E. coli isolates were found to be relatively less resistant to imipenem (2.4%), cefepime (34.1%), and ciprofloxacin (35.4%). For K. pneumonia isolates, high resistance rates were observed for piperacillin (81.6%), levofloxacin (78.9%), ampicillin (76.3%), cefotaxime (73.7%), trimethoprim-sulfamethoxazole (71.1%), ceftazidime (65.8%), gentamicin (63.2%), cefepime (50.0%), and aztreonam (44.7%). However, moderate resistance rates were detected for these were found to be less resistant for imipenem (13.2%), ceftriaxone (31.6%), and ciprofloxacin (36.8%).. E. coli and K. pneumoniae from the clinical isolates displayed high resistance to many antibiotics in UTI patients.

Topics: Ampicillin; Anti-Bacterial Agents; Aztreonam; Cefepime; Ceftazidime; Ceftriaxone; Ciprofloxacin; Drug Resistance, Multiple; Escherichia coli; Escherichia coli Infections; Gentamicins; Humans; Imipenem; Klebsiella Infections; Klebsiella pneumoniae; Levofloxacin; Microbial Sensitivity Tests; Piperacillin; Prevalence; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

To compare the bacterial killing and emergence of resistance of intermittent versus prolonged (extended and continuous infusions) infusion dosing regimens of piperacillin/tazobactam against two Escherichia coli clinical isolates in a dynamic hollow-fibre infection model (HFIM).. Three piperacillin/tazobactam dosing regimens (4/0.5 g 8 hourly as 0.5 and 4 h infusions and 12/1.5 g/24 h continuous infusion) against a ceftriaxone-susceptible, non-ESBL-producing E. coli 44 (Ec44, MIC 2 mg/L) and six piperacillin/tazobactam dosing regimens (4/0.5 g 8 hourly as 0.5 and 4 h infusions and 12/1.5 g/24 h continuous infusion; 4/0.5 g 6 hourly as 0.5 and 3 h infusions and 16/2 g/24 h continuous infusion) were simulated against a ceftriaxone-resistant, AmpC- and ESBL-producing E. coli 50 (Ec50, MIC 8 mg/L) in a HFIM over 7 days (initial inoculum ∼107 cfu/mL). Total and less-susceptible subpopulations and MICs were determined.. All simulated dosing regimens against Ec44 exhibited 4 log10 of bacterial killing over 8 h without regrowth and resistance emergence throughout the experiment. For Ec50, there was the initial bacterial killing of 4 log10 followed by regrowth to 1011 cfu/mL within 24 h against all simulated dosing regimens, and the MICs for resistant subpopulations exceeded 256 mg/L at 72 h.. Our study suggests that, for critically ill patients, conventional intermittent infusion, or prolonged infusions of piperacillin/tazobactam may suppress resistant subpopulations of non-ESBL-producing E. coli clinical isolates. However, intermittent, or prolonged infusions may not suppress the resistant subpopulations of AmpC- and ESBL-producing E. coli clinical isolates. More studies are required to confirm these findings.

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

Resistance to third-generation cephalosporins among Gram-negative bacteria is a rapidly growing public health threat. Among the most commonly used third-generation cephalosporins is ceftriaxone. Bacterial exposure to sublethal or sub-MIC antibiotic concentrations occurs widely, from environmental residues to intermittently at the site of infection. Quality of ceftriaxone is also a concern, especially in low- and middle-income countries, with medicines having inappropriate active pharmaceutical ingredient (API) content or concentration. While focus has been largely on extended-spectrum β-lactamases and high-level resistance, there are limited data on specific chromosomal mutations and other pathways that contribute to ceftriaxone resistance under these conditions. In this work, Escherichia coli cells were exposed to a broad range of sub-MICs of ceftriaxone and mutants were analyzed using whole-genome sequencing. Low-level ceftriaxone resistance emerged after as low as 10% MIC exposure, with the frequency of resistance development increasing with concentration. Genomic analyses of mutants revealed multiple genetic bases. Mutations were enriched in genes associated with porins (

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Ceftriaxone; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Microbial Sensitivity Tests; Whole Genome Sequencing

Gut colonization by ESBL-producing Enterobacteriaceae (ESBL-PE) is widespread and is promoted by antibiotic exposure. Higher fecal abundance of ESBL-PE promotes the dissemination of the bacteria in the environment and is associated with increased risk of infection. Ceftriaxone and temocillin are commonly used antibiotics with a different activity on gut flora. Their impact on fecal abundance of ESBL-producing Enterobacteriaceae has not been studied. The objective of this study was to compare the propensity of ceftriaxone and temocillin to modify the abundance of ESBL-producing Escherichia coli in feces of colonized mice.. Mice received broad-spectrum antibiotics in order to disrupt their normal gut flora. A CTX-M-type ESBL-producing E. coli clinical isolate was then administered orally, leading to durable colonization. Thirty days later, mice received either temocillin or ceftriaxone with drinking water at a concentration simulating human intestinal exposure. Third-generation-cephalosporin resistant (3GCR) E. coli were enumerated in feces on selective medium before, 2 days and 10 days after the end of antibiotic exposure. The experiment was performed with two E. coli isolates with different temocillin minimum inhibitory concentrations.. Exposure to ceftriaxone induced an increase in the fecal abundance of 3GCR E. coli. In contrast, temocillin had no effect or transiently decreased the number of 3GCR E. coli. Results obtained with the two strains were similar.. Contrary to ceftriaxone, temocillin does not promote expansion of ESBL-producing E. coli in feces of colonized mice. Thus temocillin may be a therapeutic of choice when a temocillin-susceptible strain infection is suspected or proven to prevent the expansion of ESBL-PE in a previously colonized patient.

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; Ceftriaxone; Disease Models, Animal; Enterobacteriaceae; Escherichia coli; Escherichia coli Infections; Feces; Female; Humans; Male; Mice; Microbial Sensitivity Tests; Penicillins

Topics: Aged; Anti-Bacterial Agents; Ceftriaxone; Critical Illness; Escherichia coli Infections; Female; Hemofiltration; Humans; Hypoalbuminemia; Shock, Septic

Topics: Aged; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Ceftriaxone; Disk Diffusion Antimicrobial Tests; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Feces; Humans; Malawi; Male; Whole Genome Sequencing

Antibiotic resistance has become a major issue in public health especially for one of the most used antibiotics; the third-generation cephalosporins. One of the main resistance mechanisms in Enterobacteriaceae, is the production of Extended-Spectrum β-lactamases. Here, we demonstrated that the oligonucleotide therapy is an efficient approach to reduce the resistance of bacteria to antibiotic treatment. Lipid oligonucleotides (LONs) were proved to be efficient strategies in both delivering the oligonucleotide sequences in the prokaryotic cells and decreasing the Minimum Inhibitory Concentration of resistant bacteria to a third generation cephalosporin, the ceftriaxone. Accordingly, we demonstrated the strong antimicrobial potential of this LON strategy targeting the ß-lactamase activity on both clinical and laboratory strains. Our results support the concept that the self-delivery of oligonucleotide sequences via lipid conjugation may be extended to other antimicrobial drugs, which opens novel ways to struggle against the antibiotic resistance.

Topics: Anti-Bacterial Agents; beta-Lactamases; Ceftriaxone; Cephalosporins; Drug Carriers; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Lipids; Microbial Sensitivity Tests; Oligonucleotides

There are scarce data describing the etiology and clinical sequelae of sepsis in low- and middle-income countries (LMICs). This study describes the prevalence and etiology of sepsis among critically ill patients at a referral hospital in Malawi. We conducted an observational prospective cohort study of adults admitted to the intensive care unit or high-dependency unit (HDU) from January 29, 2018 to March 15, 2018. We stratified the cohort based on the prevalence of sepsis as defined in the following three ways: quick sequential organ failure assessment (qSOFA) score ≥ 2, clinical suspicion of systemic infection, and qSOFA score ≥ 2 plus suspected systemic infection. We measured clinical characteristics and blood and urine cultures for all patients; antimicrobial sensitivities were assessed for positive cultures. During the study period, 103 patients were admitted and 76 patients were analyzed. The cohort comprised 39% male, and the median age was 30 (interquartile range: 23-40) years. Eighteen (24%), 50 (66%), and 12 patients (16%) had sepsis based on the three definitions, respectively. Four blood cultures (5%) were positive, two from patients with sepsis by all three definitions and two from patients with clinically suspected infection only. All blood bacterial isolates were multidrug resistant. Of five patients with urinary tract infection, three had sepsis secondary to multidrug-resistant bacteria. Hospital mortality for patients with sepsis based on the three definitions ranged from 42% to 75% versus 12% to 26% for non-septic patients. In summary, mortality associated with sepsis at this Malawi hospital is high. Bacteremia was infrequently detected, but isolated pathogens were multidrug resistant.

Topics: Adult; Anti-Bacterial Agents; Antifungal Agents; Bacteremia; Burkholderia Infections; Candida glabrata; Candidiasis, Invasive; Ceftriaxone; Cohort Studies; Critical Illness; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Female; Gram-Positive Bacterial Infections; Hospital Mortality; Humans; Intensive Care Units; Klebsiella Infections; Malawi; Male; Metronidazole; Microbial Sensitivity Tests; Middle Aged; Prevalence; Prospective Studies; Proteus Infections; Sepsis; Staphylococcal Infections; Urinary Tract Infections; Young Adult

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

Cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, intravenous fosfomycin and plazomicin represent potential carbapenem sparing agents for extended-spectrum-beta-lactamase or AmpC beta-lactamase producing Escherichia coli infection. However, available data is limited in predicting the volume of carbapenem therapy which could be substituted and real-world contraindications.. We determined the number of carbapenem days of therapy (DOT) which could be substituted and frequent contraindications accounting for antimicrobial susceptibility and site of infection in an unselected cohort with ceftriaxone-non-susceptible E. coli bacteremia at a single health network from 2015 to 2016. Individual patient data was used to calculate DOT and substitution for each agent.. There were 108 episodes of E. coli bacteremia resulting in 67.2 carbapenem DOT/100 patient-days of antimicrobial therapy administered. Ceftazidime-avibactam could be used to substitute 36.2 DOT/100 patient-days (54%) for inpatient definitive therapy, ceftolozane-tazobactam for 34.7 DOT/100 patient-days (52%), cefiderocol for 27.1 DOT/100 patient-days (40%), fosfomycin for 23.3 DOT /100 patient-days (35%) and plazomicin for 27.1 DOT/100 patient-days (40%). Non-urinary tract source of infection was the most frequent contraindication to fosfomycin (25), plazomicin (26) and cefiderocol (26). Use in outpatient parenteral antimicrobial therapy (OPAT) programs accounted for 40% of DOT, all of which could be substituted if stability data allowed for ceftazidime-avibactam and ceftolozane-tazobactam.. All tested agents could be used to replace a significant volume of carbapenem therapy. Establishing stability of these agents for use in OPAT is required for maximizing their use as carbapenem sparing agents while randomized clinical data is awaited for some of these agents in resistant E. coli bacteremia.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Azabicyclo Compounds; Bacteremia; Carbapenems; Ceftazidime; Ceftriaxone; Cephalosporins; Drug Combinations; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Tazobactam

Extended spectrum β-lactamases (ESBL) producing Enterobacteriaceae predominantly E. coli and K. pneumoniae bacteremia have limited treatment options and high mortality. The objective was to determine the risk factors for in-hospital mortality particularly treatment with carbapenem versus beta lactam/beta lactamase combination (BL/BLI) in patients with ceftriaxone resistant E. coli bacteremia. A retrospective cohort study was conducted at the Aga Khan University, Karachi, Pakistan. Adult patients with sepsis and monomicrobial ceftriaxone resistant E. coli bacteremia were enrolled. Factors associated with mortality in patients were determined using logistic regression analysis.. Mortality rate was 37% in those empirically treated with carbapenem compared to 20% treated with BL/BLI combination therapy (p-value: 0.012) and was 21% in those treated with a carbapenem compared to 13% in patients definitively treated with BL/BLI combination therapy (p-value: 0.152). In multivariable logistic regression analysis, only Pitt bacteremia score of ≥ four was significantly associated with mortality (OR: 7.7 CI 2.6-22.8) while a urinary source of bacteremia was protective (OR: 0.26 CI 0.11-0.58). In-hospital mortality in patients with Ceftriaxone resistant E. coli bacteremia did not differ in patients treated with either a carbapenem or BL/BLI combination. However, Pitt bacteremia score of ≥ 4 was strongly associated with mortality.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamase Inhibitors; beta-Lactamases; Ceftriaxone; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Gene Expression; Humans; Logistic Models; Male; Middle Aged; Retrospective Studies; Risk Factors; Survival Analysis

Commonly used antibiotics exert their effects predominantly on rapidly growing bacterial cells; yet, the growth dynamics taking place during infection in a complex host environment remain largely unknown. Hence, a means to measure

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Ciprofloxacin; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Gentamicins; Mice; Peritonitis

Ceftriaxone-resistant Enterobacteriaceae are priority pathogens of critical importance.. In August 2017, we prospectively analysed. These results provide insights into sociodemographic variation in CR-EC in the community. A better understanding of this variation may inform empiric treatment guidelines and strategies to reduce community dissemination of CR-EC.

Topics: Adult; Aged; Anti-Bacterial Agents; Ceftriaxone; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Residence Characteristics; Urinary Tract Infections; Urine; Victoria

Topics: Adult; Amikacin; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Ceftriaxone; Cesarean Section; Drug Resistance, Bacterial; Endometritis; Escherichia coli; Escherichia coli Infections; Female; Fetal Membranes, Premature Rupture; Humans; India; Nucleic Acid Amplification Techniques; Ontario; Pregnancy; Pregnancy, Twin; Puerperal Infection; Travel

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

Topics: Adult; beta-Lactamases; Ceftriaxone; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Gentamicins; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Maternal-Fetal Exchange; Piperacillin, Tazobactam Drug Combination; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Infectious; Tanzania; Urinary Tract Infections; Young Adult

Supported by years of clinical use in some countries and more recently by literature on experimental models, as well as its compassionate use in Europe and in the United States, bacteriophage (phage) therapy is providing a solution for difficult-to-treat bacterial infections. However, studies of the impact of such treatments on the host remain scarce. Murine acute pneumonia initiated by intranasal instillation of two pathogenic strains of

Topics: Administration, Intranasal; Animals; Anti-Bacterial Agents; Bacteremia; Bacterial Load; Blood Cell Count; Ceftriaxone; Cytokines; Edema; Escherichia coli Infections; Lung Diseases; Male; Mice, Inbred BALB C; Myoviridae; Phage Therapy; Pneumonia; Podoviridae; Treatment Outcome

Topics: Aged, 80 and over; Anemia, Aplastic; Anti-Bacterial Agents; Bone Marrow; Ceftriaxone; Coinfection; Dermatitis, Exfoliative; Escherichia coli; Escherichia coli Infections; Humans; Injections, Intravenous; Male; Photosensitivity Disorders; Skin; Staphylococcal Skin Infections; Staphylococcus aureus

Background Urinary tract infections (UTIs) are among the most common bacterial infections. Options for initial treatment of pyelonephritis or UTI requiring hospitalization include levofloxacin (LVF) or extended-spectrum cephalosporins. Globally, uropathogenic Escherichia coli resistance rates to fluoroquinolones have increased in recent years. Objective To compare clinical outcomes of patients receiving ceftriaxone (CTX) to those who received LVF empirically for the treatment of E. coli UTI. Setting 433-bed community hospital in Lexington, KY. Methods Retrospective, single center, cohort study of adults with a urine culture positive for E. coli who received either IV LVF or CTX empirically for the treatment of UTI. Main outcome measure The primary outcome was hospital length of stay. Secondary outcomes include time to susceptible therapy (TsT), hospital cost, and susceptibility to empiric therapy. Results There was no statistically significant difference in LOS or hospital cost. Subgroup analysis compared patients that received concordant CTX treatment and patients that received discordant LVF treatment. Patients that received concordant CTX treatment had a nonsignificant shorter median LOS (4.16 vs. 6.34 days). Median hospital cost was lower ($4345 vs. $8462, p = 0.004) and median TsT was shorter (5.83 vs. 64.46 h, p < 0.001) in the concordant CTX group. Conclusion Choice of empiric antibiotic therapy should be based on local antibiogram data. For patients with UTI requiring hospitalization, CTX seems to be an effective empiric therapy for most patients. More data is required to examine the effectiveness of local and source specific antibiograms on clinical outcomes when guiding treatment of patients with UTI.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Ceftriaxone; Cohort Studies; Escherichia coli; Escherichia coli Infections; Female; Humans; Levofloxacin; Male; Middle Aged; Retrospective Studies; Urinary Tract Infections

Sepsis is a life-threatening systemic inflammatory condition triggered as a result of an excessive host immune response to infection. In the past, immunomodulators have demonstrated a protective effect in sepsis. Azithromycin (a macrolide antibiotic) has immunomodulatory activity and was therefore evaluated in combination with ceftriaxone in a clinically relevant murine model of sepsis induced by cecal ligation and puncture (CLP). First, mice underwent CLP and 3 h later were administered the vehicle or a subprotective dose of ceftriaxone (100 mg/kg of body weight subcutaneously) alone or in combination with an immunomodulatory dose of azithromycin (100 mg/kg intraperitoneally). Survival was monitored for 5 days. In order to assess the immunomodulatory activity, parameters such as plasma and lung cytokine (interleukin-6 [IL-6], IL-1β, tumor necrosis factor alpha) concentrations, the plasma glutathione (GSH) concentration, plasma and lung myeloperoxidase (MPO) concentrations, body temperature, blood glucose concentration, and total white blood cell count, along with the bacterial load in blood, peritoneal lavage fluid, and lung homogenate, were measured 18 h after CLP challenge. Azithromycin in the presence of ceftriaxone significantly improved the survival of CLP-challenged mice. Further, the combination attenuated the elevated levels of inflammatory cytokines and MPO in plasma and lung tissue and increased the body temperature and blood glucose and GSH concentrations, which were otherwise markedly decreased in CLP-challenged mice. Ceftriaxone produced a significant reduction in the bacterial load, while coadministration of azithromycin did not produce a further reduction. Therefore, the survival benefit offered by azithromycin was due to immunomodulation and not its antibacterial action. The findings of this study indicate that azithromycin, in conjunction with appropriate antibacterial agents, could provide clinical benefits in sepsis.

Topics: Animals; Azithromycin; Bacterial Load; Ceftriaxone; Disease Models, Animal; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Female; Glutathione; Inflammation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Lung; Mice; Sepsis; Tumor Necrosis Factor-alpha

Acute central nervous system (CNS) infections in children in sub-Saharan Africa are often fatal. Potential contributors include late presentation, limited diagnostic capacity and inadequate treatment. A more nuanced understanding of treatment practices with a goal of optimizing such practices is critical to prevent avoidable case fatality. We describe empiric antimicrobial treatment, antibiotic resistance and treatment adequacy in a prospective cohort of 459 children aged two months to 12 years hospitalised for suspected acute CNS infections in Mbarara, Uganda, from 2009 to 2012. Among these 459 children, 155 had a laboratory-confirmed diagnosis of malaria (case-fatality rate [CFR] 14%), 58 had bacterial infections (CFR 24%) and 6 children had mixed malaria and bacterial infections (CFR 17%). Overall case fatality was 18.1% (n = 83). Of 219 children with laboratory-confirmed malaria and/or bacterial infections, 182 (83.1%) received an adequate antimalarial and/or antibiotic on the day of admission and 211 (96.3%) within 48 hours of admission. The proportion of those receiving adequate treatment was similar among survivors and non-survivors. All bacterial isolates were sensitive to ceftriaxone except one Escherichia coli isolate with extended-spectrum beta-lactamase (ESBL). The observed high mortality was not a result of inadequate initial antimicrobial treatment at the hospital. The epidemiology of CNS infection in this setting justifies empirical use of a third-generation cephalosporin, however antibiotic resistance should be monitored closely.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactamases; Ceftriaxone; Central Nervous System Infections; Child; Child, Preschool; Coinfection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Infant; Malaria; Male; Uganda

We report a case of Escherichia coli infection of a cephalohematoma in an infant delivered by vacuum extraction. After excluding potential complications, the patient was treated with intravenous ceftriaxone while hospitalized followed by oral cephalexin after discharge. Infection is a rare but serious complication of cephalohematomas in the newborn period. Escherichia coli is the most common pathogen responsible for infected cephalohematomas. Clinicians should be aware that infected cephalohematomas may be complicated by sepsis, meningitis, or osteomyelitis.

Topics: Anti-Bacterial Agents; Birth Injuries; Ceftriaxone; Craniocerebral Trauma; Escherichia coli Infections; Hematoma; Humans; Infant; Male; Vacuum Extraction, Obstetrical

Hemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in children, with the majority of cases caused by an infection with Shiga toxin-producing Escherichia coli (STEC). Whereas O157 is still the predominant STEC serotype, non-O157 serotypes are increasingly associated with STEC-HUS. However, little is known about this emerging and highly diverse group of non-O157 serotypes. With supportive therapy, STEC-HUS is often self-limiting, with occurrence of chronic sequelae in just a small proportion of patients.. In this case report, we describe a 16-month-old boy with a highly severe and atypical presentation of STEC-HUS. Despite the presentation with multi-organ failure and extensive involvement of central nervous system due to extensive thrombotic microangiopathy (suggestive of atypical HUS), fecal diagnostics revealed an infection with the rare serotype: shiga toxin 2d-producing STEC O80:H2.. This report underlines the importance of STEC diagnostic tests in all children with HUS, including those with an atypical presentation, and emphasizes the importance of molecular and serotyping assays to estimate the virulence of an STEC strain.

Topics: Anti-Bacterial Agents; Antibodies, Monoclonal, Humanized; Biopsy; Blood Culture; Ceftriaxone; Escherichia coli Infections; Hemolytic-Uremic Syndrome; Humans; Infant; Liver; Magnetic Resonance Imaging; Male; Midazolam; Multiple Organ Failure; Real-Time Polymerase Chain Reaction; Resuscitation; Serotyping; Shiga Toxin 2; Shiga-Toxigenic Escherichia coli; Thrombotic Microangiopathies; Virulence

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Ceftriaxone; Cyclophosphamide; Diagnosis, Differential; Escherichia coli Infections; Female; Groin; Humans; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Penicillanic Acid; Piperacillin; Positron-Emission Tomography; Rituximab; Tazobactam; Tomography, X-Ray Computed; Vincristine

Topics: Anti-Bacterial Agents; Ceftriaxone; Escherichia coli Infections; Feces; Female; Humans; Infant; Infusions, Intravenous; Lithiasis; Risk

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

The management of bloodstream infection, a life-threatening disease, largely relies on early detection of infecting microorganisms and accurate determination of their antibiotic susceptibility to reduce both mortality and morbidity. Recently we developed a new technique based on atomic force microscopy capable of detecting movements of biologic samples at the nanoscale. Such sensor is able to monitor the response of bacteria to antibiotic's pressure, allowing a fast and versatile susceptibility test. Furthermore, rapid preparation of a bacterial pellet from a positive blood culture can improve downstream characterization of the recovered pathogen as a result of the increased bacterial concentration obtained.. Using artificially inoculated blood cultures, we combined these two innovative procedures and validated them in double-blind experiments to determine the susceptibility and resistance of Escherichia coli strains (ATCC 25933 as susceptible and a characterized clinical isolate as resistant strain) towards a selection of antibiotics commonly used in clinical settings.. On the basis of the variance of the sensor movements, we were able to positively discriminate the resistant from the susceptible E. coli strains in 16 of 17 blindly investigated cases. Furthermore, we defined a variance change threshold of 60% that discriminates susceptible from resistant strains.. By combining the nanomotion sensor with the rapid preparation method of blood culture pellets, we obtained an innovative, rapid and relatively accurate method for antibiotic susceptibility test directly from positive blood culture bottles, without the need for bacterial subculture.

Topics: Ampicillin; Anti-Bacterial Agents; Bacteremia; Blood Culture; Ceftriaxone; Ciprofloxacin; Double-Blind Method; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Microscopy, Atomic Force; Nanotechnology

In the present study, enhancement of the the antibacterial activity of ceftriaxone against Gram-positive (meticillin-resistant Staphylococcus aureus; MRSA) and Gram-negative (Escherichia coli) bacteria with a biodegradable polymer was attempted.. MRSA and E. coli were collected and identified by biochemical and molecular tests. Blank and ceftriaxone-loaded chitosan nanoparticles (CNPs) were prepared by the ionic gelation method. In vitro antibiotic-susceptibility studies were performed by disc diffusion, agar well plate method, Etest and time-kill assay. In vivo activity was assessed using the neutropenic mouse thigh model and cytotoxicity was estimated by MTT (methylthiazolyldiphenyl tetrazolium bromide) assay with the MCF-7 cancer cell line.. MRSA showed 97 % and E. coli 83 % resistance against ceftriaxone in the disc diffusion test. The isolates showing a ≥1024 mg l-1 MIC value for ceftriaxone were selected for further evaluation. In the agar well plate method, the mean zones of inhibition for blank and ceftriaxone-loaded CNPs were 17 and 23 mm, respectively, for MRSA isolates and 15 and 25 mm, respectively, for E. coli isolates. In the time-kill assay, ~1 log10 to ~2.5 log10 reduction in viability was seen with both isolates when treated with ceftriaxone-loaded CNPs over 24 h. The in vivo studies also showed the enhanced antibacterial activity of ceftriaxone-loaded CNPs, with a 41 % reduction in MRSA and a 27 % reduction in E. coli burden. A low cytotoxicity of blank and ceftriaxone-loaded CNPs was seen, with a slight reduction in the percentage viability of cells from 87 to 83 % and from 88 to 81 %, respectively.. The synergistic effect of ceftriaxone-loaded CNPs is a useful finding for the treatment of MRSA and E. coli infections.

Topics: Animals; Anti-Bacterial Agents; Biocompatible Materials; Ceftriaxone; Chitosan; Disease Models, Animal; Drug Synergism; Escherichia coli; Escherichia coli Infections; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Microbial Viability; Nanoparticles; Neutropenia; Staphylococcal Infections

The emergence of resistant Escherichia coli to fluoroquinolones (FQs) is of growing concern, yet the latest guidelines for the treatment of pyelonephritis still recommend FQs as first-line treatment. Our primary objective was to determine the impact of discordant prescribing of FQs in E coli pyelonephritis on hospital length of stay (LOS) and early clinical response (ECR).. We retrospectively compared discordant and concordant prescribing of FQs for LOS and ECR. We also compared FQs, ceftriaxone, piperacillin/tazobactam, and carbapenems for these clinical outcomes.. Forty-nine patients included in the comparison between discordant (n = 9) and concordant (n = 40) prescribing of FQs. There was significantly lower ECR in patients with discordant prescribing of FQs (38 of 40, 95% vs 5 of 9, 55.6%, P = .0074) and a trend toward longer LOS (4 [2.3] days vs 3 [2.0] days, P = .0571). Illness severity, estimated using Simplified Acute Physiology Score (SAPS II) score, was similar between groups (P = .717).. There was a significantly decreased ECR and a trend toward increased LOS when FQs were used in FQ-resistant E coli. Regarding alternative treatment for E coli pyelonephritis, ceftriaxone was as effective as concordant FQs and significantly better than discordant FQs.

Topics: Adult; Anti-Bacterial Agents; Carbapenems; Ceftriaxone; Drug Resistance, Bacterial; Escherichia coli Infections; Female; Fluoroquinolones; Guidelines as Topic; Humans; Length of Stay; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pyelonephritis; Retrospective Studies; Treatment Outcome

Topics: Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Male; Middle Aged; Plasmids

Literature is lacking regarding the utilization of first-generation cephalosporins for the treatment of acute pyelonephritis. The aim of this study was to determine whether cefazolin is non-inferior to ceftriaxone for the empirical treatment of acute pyelonephritis in hospitalized patients. The primary outcome included a composite of symptomatic resolution plus either defervescence at 72 h or normalization of serum white blood cell count at 72 h (non-inferiority margin 15%). Secondary outcomes included length of stay and 30 day readmission. A subgroup analysis of the composite outcome was also conducted for imaging-confirmed pyelonephritis.. This was a retrospective, non-inferiority, multicentre, cohort study comparing cefazolin versus ceftriaxone for the empirical treatment of acute pyelonephritis in hospitalized patients.. Overall, 184 patients received one of the two treatments between July 2009 and March 2015. The composite outcome was achieved in 80/92 (87.0%) in the cefazolin group versus 79/92 (85.9%) in the ceftriaxone group (absolute difference 1.1%, 95% CI -11.1% to 8.9%, P = 0.83), meeting the pre-defined criteria for non-inferiority. The composite outcome for patients with imaging-confirmed pyelonephritis was achieved in 46/56 (82.1%) versus 42/50 (84.0%) for the cefazolin group and the ceftriaxone group, respectively (absolute difference 1.9%, 95% CI -12.8% to 16.5%, P = 0.80). Additionally, there were no statistically significant differences in length of stay or 30 day readmission for cystitis or pyelonephritis.. Cefazolin was non-inferior to ceftriaxone with regard to clinical response for the treatment of hospitalized patients with acute pyelonephritis in this study. No difference was observed for length of stay or 30 day readmission.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cefazolin; Ceftriaxone; Cephalosporins; Cohort Studies; Empirical Research; Escherichia coli; Escherichia coli Infections; Female; Hospitalization; Humans; Length of Stay; Leukocyte Count; Male; Middle Aged; Patient Readmission; Pyelonephritis; Retrospective Studies; Young Adult

The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistant E. coli and K. pneumoniae isolates should include resistance mechanisms when possible.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Aztreonam; Bacterial Proteins; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Infant; Infant, Newborn; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Prospective Studies; Young Adult

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

Topics: Anti-Bacterial Agents; Ceftriaxone; Child, Preschool; Emphysema; Escherichia coli; Escherichia coli Infections; Female; Humans; Kidney; Nephrectomy; Pyelitis; Tomography, X-Ray Computed

To assess the rates of infectious complications before and after the change of prophylactic antibiotic regimens in prostate needle biopsy.. The records of 5,577 patients who underwent prostate needle biopsy at Asan Medical Center between August 2005 and July 2012 were retrospectively reviewed. Group 1 (n=1,743) included patients treated between 2005 and 2009 with fluoroquinolone for 3 days, group 2 (n=2,723) included those treated between 2009 and 2012 with ceftriaxone once before the biopsy and fluoroquinolone before biopsy and continue therapy for 3 days, and group 3 (n=1,111) received the same treatment for more than 7 days after the biopsy. Univariable and multivariable logistic regression models addressed risk factors associated with infectious complication after prostate needle biopsy.. Infectious complication after prostate needle biopsy developed in 18 (group 1), seven (group 2), and two patients (group 3) (p=0.001). In group 1, seven patients with infectious complication had positive blood cultures and harbored fluoroquinolone-resistant Escherichia coli, four had ceftriaxone susceptible isolates, and three had extended spectrum beta-lactamase-positive E. coli. Two patients in group 1 required intensive care because of septic shock. In multivariable analysis, the patients with combination of fluoroquinolone and ceftriaxone had significantly lower infectious complication rate than the fluoroquinolon alone (p=0.003).. Antibiotic prophylaxis with ceftriaxone and fluoroquinolone before prostate needle biopsy decreased the risk of potentially serious infectious complications.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibiotic Prophylaxis; Biopsy, Needle; Ceftriaxone; Cross Infection; Drug Evaluation; Drug Resistance, Bacterial; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Humans; Incidence; Male; Middle Aged; Prostatic Neoplasms; Republic of Korea; Retrospective Studies; Ultrasonography, Interventional; Young Adult

To describe the practical problems related to urinary tract infection (UTI) management in febrile Vietnamese children.. During a prospective 28-month inclusion period, 143 febrile children with significant bacteriuria were treated for UTI in the nephrology department of Nhi Dong 2 children's hospital in Ho Chi Minh City, Vietnam. Patients were treated after blood and urine samples had been taken for culture, according to a local antibiotic protocol, parenterally with ceftriaxone 75mg/kg/day. Oral treatment with cefixime 8mg/kg/day was started after 48h of apyrexia for 2 weeks. According to local protocol, antibiotic therapy was only changed if children did not respond clinically to treatment regardless of antibiogram results.. Among these 143 children, 51% were girls and 80% of them had their first UTI before the age of 2 years. The commonest causative agent was Escherichia coli (80% of cases) with a high resistance rate to ampicillin (91%) and cotrimoxazole (74%). Extended-spectrum β-lactamase (ESBL) production was observed in 52% of Enterobacteriaceae isolates. According to antibiotic susceptibility, the initial treatment with ceftriaxone was found to be inappropriate in 63% of cases.. E. coli was responsible for 80% of UTIs in Vietnamese children with a high rate of resistance to first-line antibiotics. ESBL production was found to be extremely high in this study. Based on these data, we propose a new empiric treatment schedule for Vietnamese children suspected of UTI.

Topics: Adolescent; Anti-Bacterial Agents; Ceftriaxone; Child; Child, Preschool; Escherichia coli Infections; Female; Fever; Humans; Infant; Male; Prospective Studies; Urinary Tract Infections

An increase in fluoroquinolone resistance and transrectal ultrasound-guided prostate (TRUS) biopsy infections has prompted the need for alternative effective antibiotic prophylaxis. We aimed to compare ciprofloxacin and other single-agent therapies to combination therapy for efficacy and adverse effects. Men who underwent a TRUS biopsy within the VA Boston health care system with documented receipt of prophylactic antibiotics periprocedure were eligible for inclusion. Postprocedure infections within 30 days were ascertained by chart review from electronic records, including any inpatient, outpatient, or urgent-care visits. Among 455 evaluable men over a 3-year period, there were 25 infections (5.49%), with sepsis occurring in 2.4%, urinary tract infections (UTI) in 1.54%, and bacteremia in 0.44% of patients. Escherichia coli was the most common urine (89%) and blood (92%) pathogen, with fluoroquinolone resistance rates of 88% and 91%, respectively. Ciprofloxacin alone was associated with significantly more infections than ciprofloxacin plus an additional agent (P = 0.014). Intramuscular gentamicin alone was also significantly associated with a higher infection rate obtained with all other regimens (P = 0.004). Any single-agent regimen, including ciprofloxacin, ceftriaxone, or gentamicin, was associated with significantly higher infection rates than any combination regimen (odds ratio [OR], 4; 95% confidence interval [CI], 1.47, 10.85; P = 0.004). Diabetes, immunosuppressive condition or medication, hospitalization within the previous year, and UTI within the previous 6 months were not associated with infection risk. Clostridium difficile infections were similar. These findings suggest that ciprofloxacin, ceftriaxone, and gentamicin alone are inferior to a combination regimen. Institutions with high failure rates of prophylaxis for TRUS biopsies should consider combination regimens derived from their local data.

Topics: Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacteremia; Biopsy; Ceftriaxone; Ciprofloxacin; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Gentamicins; Humans; Male; Middle Aged; Prostate; Retrospective Studies; Sepsis; Ultrasound, High-Intensity Focused, Transrectal; Urinary Tract Infections

Cefepime is frequently prescribed to treat infections caused by AmpC-producing Gram-negative bacteria. CMY-2 is the most common plasmid-mediated AmpC (pAmpC) β-lactamase. Unfortunately, CMY variants conferring enhanced cefepime resistance have been reported. Here, we describe the evolution of CMY-2 to an extended-spectrum AmpC (ESAC) in clonally identical Escherichia coli isolates obtained from a patient. The CMY-2-producing E. coli isolate (CMY-2-Ec) was isolated from a wound. Thirty days later, one CMY-33-producing E. coli isolate (CMY-33-Ec) was detected in a bronchoalveolar lavage fluid sample. Two weeks before the isolation of CMY-33-Ec, the patient received cefepime. CMY-33-Ec and CMY-2-Ec were identical by repetitive extragenic palindromic-PCR (rep-PCR), being of hyperepidemic sequence type 131 (ST131) but showing different β-lactam MICs (e.g., cefepime MIC, 16 and ≤ 0.5 μg/ml for CMY-33-Ec and CMY-2-Ec, respectively). Identical CMY-2-Ec isolates were also found in a rectal swab. CMY-33 differs from CMY-2 by a Leu293-Ala294 deletion. Expressed in E. coli strain DH10B, both CMYs conferred resistance to ceftazidime (≥ 256 μg/ml), but the cefepime MICs were higher for CMY-33 than CMY-2 (8 versus 0.25 μg/ml, respectively). The kcat/Km or inhibitor complex inactivation (kinact)/Ki app (μM(-1) s(-1)) indicated that CMY-33 possesses an extended-spectrum β-lactamase (ESBL)-like spectrum compared to that of CMY-2 (e.g., cefoxitin, 0.2 versus 0.4; ceftazidime, 0.2 versus not measurable; cefepime, 0.2 versus not measurable; and tazobactam, 0.0018 versus 0.0009, respectively). Using molecular modeling, we show that a widened active site (∼ 4-Å shift) may play a significant role in enhancing cefepime hydrolysis. This is the first in vivo demonstration of a pAmpC that under cephalosporin treatment expands its substrate spectrum, resembling an ESBL. The prevalence of CMY-2-Ec isolates is rapidly increasing worldwide; therefore, awareness that cefepime treatment may select for resistant isolates is critical.

Topics: Aged; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cefepime; Ceftriaxone; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Humans; Male; Microbial Sensitivity Tests; Molecular Docking Simulation

Ceftriaxone is frequently administered empirically for hospitalized patients with acute pyelonephritis (APN) due to prevalent quinolone resistance in our hospital; however, its use is inappropriate for extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, an increasing problem.. A retrospective, 1:2 matched cohort study was performed to evaluate the impact of ESBL on APN treated with empirical ceftriaxone. Each patient in ESBL group was matched with two patients in the non-ESBL group, using a 16-point scoring system, which included age, sex, bacteremia, simplified acute physiology score 2, Charlson comorbidity index and APN severity score.. From 2009 to 2011, among 1,322 community-onset cases of the E. coli bacteriuria with 212 (16%) ESBL producers, 261 patients with APN were treated empirically with ceftriaxone in a secondary care hospital. Among these 261 cases, twenty-six patients in the ESBL group and 52 matched patients in the non-ESBL group (1:2) were included. Mean time to defervescence was 4.6±2.2 days in the ESBL group and 2.6±1.3 days in the non-ESBL group (p<0.01). Rate of microbiological resolution within 5 days after antibiotic treatment was 77% (17/22) in the ESBL group and 100% (45/45) in the non-ESBL group (p=0.01). The duration of hospitalization was 13.3±8.2 days in the ESBL group and 7.3±3.5 days in the non-ESBL group (p<0.01). No patient died in either group.. Empirical ceftriaxone therapy for APN caused by ESBL-producing E. coli is inappropriate, and consequently can delay recovery and result in longer hospitalization.

Topics: Acute Disease; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Case-Control Studies; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Female; Gene Expression; Humans; Length of Stay; Male; Microbial Sensitivity Tests; Middle Aged; Pyelonephritis; Retrospective Studies; Treatment Outcome

Antibiotic resistance in Gram-negative bacteria, especially Enterobacteriaceae, can be conferred by a large number of different acquired resistance genes, although it appears that relatively few dominate. A previous survey of Escherichia coli and Klebsiella pneumoniae isolates from Sydney, Australia, revealed that a limited set of genes could reliably predict resistance to third-generation cephalosporins (3GCs) and aminoglycosides. Here we tested E. coli and K. pneumoniae isolates with a cefotaxime, ceftriaxone and/or ceftazidime minimum inhibitory concentration of ≥ 2 μg/mL from China and Singapore, with significantly higher resistance rates than Australia, as well as the USA. Few targets were needed to predict non-susceptibility to 3GCs (95/95; 100%) and gentamicin (47/51; 92%). The gene types detected here are consistent with previous surveys in similar countries with similar resistance rates, where the majority of 3GC resistance can be explained by blaCTX-M genes. This study identified a limited set of genes capable of predicting resistance to 3GC and aminoglycoside antibiotics and implies a restriction in the global resistance gene pool that can be exploited for diagnostic purposes.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftazidime; Ceftriaxone; China; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Genes, Bacterial; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Singapore; United States

Neonatal Escherichia coli meningitis continues to be an important cause of mortality and morbidity in newborns worldwide. The aim of this study was to investigate the cytokines/chemokines, brain-derived neurotrophic factor (BDNF) levels, blood-brain barrier integrity in neonatal rats following E. coli K1 experimental meningitis infection and subsequent behavioural parameters in adulthood. In the hippocampus, interleukin increased at 96 h, IL-6 at 12, 48 and 96 h, IL-10 at 96 h, cytokine-induced neutrophil chemoattractant-1 at 6, 12, 24, 48 and 96 h, and BDNF at 48 and 96 h. In the cerebrospinal fluid, tumour necrosis factor alpha levels increased at 6, 12, 24, 48 and 96 h. The BBB breakdown occurred at 12 h in the hippocampus, and at 6h in the cortex. We evaluated behavioural parameters in adulthood: habituation to the open-field, step-down inhibitory avoidance, object recognition, continuous multiple-trials step-down inhibitory avoidance and forced swimming tasks. In adulthood, the animals showed habituation and aversive memory impairment. The animals needed a significant increase in the number of training periods to learn and not had depressive-like symptoms.

Topics: Animals; Animals, Newborn; Anti-Bacterial Agents; Avoidance Learning; Blood-Brain Barrier; Brain-Derived Neurotrophic Factor; Ceftriaxone; Cytokines; Disease Models, Animal; Escherichia coli Infections; Gene Expression Regulation, Bacterial; Learning Disabilities; Male; Memory Disorders; Meningitis, Bacterial; Rats; Rats, Wistar; Reaction Time; Recognition, Psychology; Time Factors

This study aimed to demonstrate if the addition of anti-inflammatory treatment to antibiotic therapy shows any superiority to the treatment with antibiotic only.. Forty-nine Wistar rats were divided into 7 groups. Pyelonephritis was performed by E. coli injection to upper pole of kidneys except control group. Group 2 was not treated. Ceftriaxone, ketoprofen, "ceftriaxone + ketoprofen," methylprednisolone, and "ceftriaxone + methylprednisolone" were given in the groups. The technetium-99m-dimercaptosuccinic acid scintigraphies were performed in 3rd day to detect pyelonephritis and 10th week to detect renal scarring. All kidneys were also histopathologically evaluated.. When 3rd day and 10th week scintigraphies were compared, initial 2.00 ± 0.30 point pyelonephritis score resulted in 0.71 ± 0.36 renal scar score in "ceftriaxone + ketoprofen" group (P = 0.039). Initial 2.00 ± 0.43 point pyelonephritis score resulted in 0.86 ± 0.26 renal scar score in "ceftriaxone + methylprednisolone" group (P = 0.041). Renal scar score was declined in "ceftriaxone + ketoprofen" group and "ceftriaxone + methylprednisolone" group compared with no-treatment group on 10th week of the study (P = 0.026, P = 0.044). On histopathological evaluation, it was seen that renal scar prevalence and expansion declined significantly in "ceftriaxone + ketoprofen and ceftriaxone + methylprednisolone" (P = 0.011, P = 0.023).. It was evidenced that ceftriaxone treatment in combination with ketoprofen or methylprednisolone declined scar formation in scintigraphic and histopathologic examinations of the kidneys.

Topics: Acute Disease; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Ceftriaxone; Cicatrix; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Ketoprofen; Methylprednisolone; Pyelonephritis; Radionuclide Imaging; Radiopharmaceuticals; Rats; Technetium Tc 99m Dimercaptosuccinic Acid

To investigate the therapeutic effect of E5564 (a clinically used TLR4 inhibitor) in murine abdominal sepsis elicited by intraperitoneal infection with a highly virulent Escherichia coli in the context of concurrent antibiotic therapy.. Mice were infected with different doses (~2 × 10(4)-2 × 10(6) CFU) of E. coli O18:K1 and treated after 8 h with ceftriaxone 20 mg/kg i.p. combined with either E5564 10 mg/kg i.v. or vehicle. For survival studies this treatment was repeated every 12 h. Bacterial loads and inflammatory parameters were determined after 20 h in peritoneal lavage fluid, blood, liver and lung tissue. Plasma creatinin, AST, ALT and LDH were determined to assess organ injury.. E5564 impaired bacterial clearance under the antibiotic regime after infection with a low dose E. coli (1.7 × 10(4) CFU) while renal function was slightly preserved. No differences were observed in bacterial load and organ damage after infection with a tenfold higher (1.7 × 10(5) E. coli) bacterial dose. While treatment with E5564 slightly attenuated inflammatory markers provoked by the sublethal doses of 104-105 E. coli under the antibiotic regime, it did not affect lethality evoked by infection with 1.7 × 106 E. coli.. The impact of TLR4 inhibition during abdominal sepsis by virulent E. coli bacteria is only beneficial at low infection grade at cost of bactericidal activity.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ascitic Fluid; Bacterial Load; Ceftriaxone; Cytokines; Escherichia coli; Escherichia coli Infections; Female; Lipid A; Liver; Lung; Mice, Inbred C57BL; Peritoneal Lavage; Peritonitis; Sepsis; Toll-Like Receptor 4

Urinary tract infections (UTIs) due to extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae in children are becoming more frequent, and they are commonly treated initially with a second- or third-generation cephalosporin. We developed a murine model of ascending UTI caused by ESBL-producing Escherichia coli. Using this model, we investigated the renal bacterial burden, interleukin-6 (IL-6) expression, and histopathological alterations caused by ESBL- and non-ESBL-producing bacteria after 1, 2, or 6 days with or without ceftriaxone therapy. The renal bacterial burden, IL-6 concentration, and histological inflammatory lesions were not significantly different between mice infected with ESBL- and non-ESBL-producing bacteria without treatment at any of the time points examined. Following ceftriaxone administration, the bacterial burden was eliminated in the kidneys of mice infected with ESBL- and non-ESBL-producing bacteria on the 6th postinfection day. The histological analysis demonstrated that among mice treated with ceftriaxone, those infected with ESBL-producing bacteria had more profound renal alterations than those infected with non-ESBL-producing bacteria on the 6th day (P < 0.001). In comparison, microbiological outcomes did not differ significantly between mice infected with ESBL- and non-ESBL-producing bacteria at any of the time points examined. The effectiveness of ceftriaxone in mice with UTIs due to ESBL-producing E. coli may have therapeutic implications; it is, however, hampered by limited activity on the histopathological lesions, a finding that needs further investigation.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; beta-Lactamases; Ceftriaxone; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Female; Gene Expression; Interleukin-6; Kidney; Mice; Mice, Inbred BALB C; Pyelonephritis; Treatment Outcome

Uropathogenic E. coli (UPEC) strains are described as extraintestinal pathogenic E. coli with preference for the urinary tract. Bottone et al2 recently described the first documentation of a hypermucoviscous phenotype of a UPEC strain that displays a "stringing" phenomenon analogous to those produced by Klebsiella pneumonia strains known to invade the liver. The occurrence of this hypermucoviscous phenotype of UPEC strains causing urinary tract infection has not been well established. Following, we present a case report of two separate renal isolates from a patient with recurrent renal abscesses yielding the aforementioned hypermucoviscous phenotype of UPEC strains.

Topics: Abscess; Anti-Bacterial Agents; Ceftriaxone; Ciprofloxacin; Drainage; Escherichia coli Infections; Female; Humans; Kidney Diseases; Middle Aged; Phenotype; Tomography, X-Ray Computed; Urinary Tract; Urinary Tract Infections; Uropathogenic Escherichia coli

To measure the effect of a voluntary ban on cephalosporin usage in the Danish pig production on the prevalence of extended-spectrum cephalosporinase (ESC)-producing Escherichia coli in pigs and pork.. Data on cephalosporin consumption were obtained from the VetStat database. For detection of ESC-producing E. coli, three sampling types were included: at slaughter, caecal samples were collected from pigs in 2009 and 2010 (June) before and in two periods (2010 and 2011) after a voluntary ban on cephalosporins was effected (July 2010); at farm level, pools of five stool samples from different pigsties were collected in 2010 and in 2011; and samples from pork were collected randomly at retail stores and outlets from 2009 to 2011. ESC-producing E. coli was isolated after selective enrichment in MacConkey broth with 1 mg/L ceftriaxone. ESC genes were detected using PCR, microtube array and sequencing.. From July 2010 the consumption of cephalosporins approximated zero. The occurrence of ESC-producing E. coli in pigs at slaughter was not significantly different (P=0.7) between 2009 [10.8% (85/786)] and 2010 [11.8% (48/407)], but in 2011 the occurrence [3.6% (28/777)] decreased significantly (P<0.001). A significant decrease (P=0.002) in occurrence of ESC-producing E. coli at pig farm level from 2010 [11% (11/99)] to 2011 (0/78) was also observed. The bla(CTX-M-1) gene was most often detected (63%), but bla(CTX-M-14) and bla(CTX-M-15) were also found. Occurrence in pork was between 1.3% and 0.9%.. The discontinuation of an already low use of cephalosporins in pig production has significantly reduced the occurrence of ESC-producing E. coli.

Topics: Animal Husbandry; Animals; Anti-Bacterial Agents; beta-Lactam Resistance; Carrier State; Cecum; Ceftriaxone; Cephalosporinase; Cephalosporins; Denmark; Diet; DNA, Bacterial; Escherichia coli; Escherichia coli Infections; Feces; Polymerase Chain Reaction; Prevalence; Swine

Topics: Adult; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; DNA, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Genotype; Humans; Microbial Sensitivity Tests; Molecular Sequence Data; Sequence Analysis, DNA; Treatment Failure

This study aims to scrutinize the hospitalized patients with the diagnosis of acute prostatitis after transrectal ultrasound-guided biopsy of the prostate (TRUSBP) focusing their history of previous antibiotic use, clinical pictures, microbiologic features, and resistance patterns of the isolates.. A retrospective evaluation of the records between 2005 and 2010 revealed 13 patients. All patients received ciprofloxacin 500 mg twice a day starting from the day before TRUSBP for 5 days.. Positive 13 urine and 7 blood samples (Escherichia coli in 12 patients, Enterococcus species in one) were evaluated for resistance patterns. All were resistant to fluoroquinolones. Extended spectrum beta-lactamase producing E. coli isolated in 4 patients were treated with carbapenems. Empirical ceftriaxone was shifted to carbapenem (4 patients), vancomycin (1 patient). Empirical carbapenem was maintained in 5 patients. Seven patients with elevated PSA received fluoroquinolones for 4 weeks before TRUSBP on the assumption that they had subclinical infectious prostatitis. Previous exposure to fluoroquinolones did not lead to important differences in respect to the studied parameters.. The prompt initiation of effective treatment is essential to decrease morbidity and mortality. Empirical treatment would be a second or third generation cephalosporins, or carbapenems according to clinical severity of patients.

Topics: Aged; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Biopsy; Carbapenems; Ceftriaxone; Ciprofloxacin; Drug Resistance, Multiple, Bacterial; Enterococcus; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatitis; Retrospective Studies; Vancomycin

We investigated the efficiency of the cephamycin cefoxitin as an alternative to carbapenems for the treatment of urinary tract infections (UTIs) due to Escherichia coli producing CTX-M-type extended-spectrum β-lactamases. The susceptible, UTI-inducing E. coli CFT073-RR strain and its transconjugant CFT073-RR Tc (pbla(CTX-M-15)), harboring a bla(CTX-M-15) carrying-plasmid, were used for all experiments. MICs of cefoxitin (FOX), ceftriaxone (CRO), imipenem (IMP), and ertapenem (ETP) for CFT073-RR and CFT073-RR Tc (pbla(CTX-M-15)) were 4 and 4, 0.125 and 512, 0.5 and 0.5, and 0.016 and 0.032 μg/ml, respectively. Bactericidal activity was similarly achieved in vitro against the two strains after 3 h of exposure to concentrations of FOX, IMI, and ETP that were 2 times the MIC, whereas CRO was not bactericidal against CFT073-RR Tc (pbla(CTX-M-15)). The frequencies of spontaneous mutants of the 2 strains were not higher for FOX than for IMP or ETP. In the murine model of UTIs, mice infected for 5 days were treated over 24 h. Therapeutic regimens in mice (200 mg/kg of body weight every 3 h or 4 h for FOX, 70 mg/kg every 6 h for CRO, 100 mg/kg every 2 h for IMP, and 100 mg/kg every 4 h for ETP) were chosen in order to reproduce the percentage of time that free-drug concentrations above the MIC are obtained in humans with standard regimens. All antibiotic regimens produced a significant reduction in bacterial counts (greater than 2 log(10) CFU) in kidneys and bladders for both strains (P < 0.001) without selecting resistant mutants in vivo, but the reduction obtained with CRO against CFT073-RR Tc (pbla(CTX-M-15)) in kidneys was significantly lower than that obtained with FOX. In conclusion, FOX appears to be an effective therapeutic alternative to carbapenems for the treatment of UTIs due to CTX-M-producing E. coli.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; beta-Lactamases; beta-Lactams; Carbapenems; Cefoxitin; Ceftriaxone; Conjugation, Genetic; Disease Models, Animal; Drug Administration Schedule; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Humans; Imipenem; Kidney; Mice; Microbial Sensitivity Tests; Mutation Rate; Plasmids; Urinary Bladder; Urinary Tract Infections

This study examines in vitro antimicrobial resistance data from Escherichia coli isolates obtained from urine samples of U.S. outpatients between 2000 and 2010 using The Surveillance Network (TSN). Antimicrobial susceptibility results (n = 12,253,679) showed the greatest increases in E. coli resistance from 2000 to 2010 for ciprofloxacin (3% to 17.1%) and trimethoprim-sulfamethoxazole (TMP-SMX) (17.9% to 24.2%), whereas nitrofurantoin (0.8% to 1.6%) and ceftriaxone (0.2% to 2.3%) showed minimal change. From 2000 to 2010, the antimicrobial resistance of urinary E. coli isolates to ciprofloxacin and TMP-SMX among outpatients increased substantially.

Topics: Ceftriaxone; Cephalosporin Resistance; Ciprofloxacin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Nitrofurantoin; Outpatients; Population Surveillance; Trimethoprim Resistance; Trimethoprim, Sulfamethoxazole Drug Combination; United States; Urinary Tract Infections

In this study, the cooperative antibacterial efficiency of CdTe quantum dots (QDs) and rocephin against Escherichia coli (E. coli) was investigated. Colony-forming capability assay and diameter of inhibition zone (DIZ) measurement showed the antibiotic action of CdTe QDs-rocephin complex was better than the superposition of pure CdTe QDs and rocephin. The fractional inhibitory concentration index (FICI) indicated that CdTe QDs-rocephin complex could achieve great cooperative antimicrobial effects. The infrared ray (IR) spectrum, photoluminescence (PL) spectrophotometry, and detection of reactive oxygen species (ROS) indicated that CdTe QDs and rocephin formed a stable antimicrobial group through electrostatic attraction and hydrogen bonds and then killed the E. coli together. Meanwhile, the fluorescence intensity of CdTe QDs and the optical density (OD) value of E. coli showed a good linear relationship. Thus, dynamic monitoring to total bacterial concentration in the antibacterial process was realized by the CdTe QDs.

Topics: Anti-Bacterial Agents; Cadmium Compounds; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Humans; Microbial Sensitivity Tests; Quantum Dots; Tellurium

The objective of this study was to investigate the association between ceftiofur use policy in finishing swine barns and recovery of fecal Escherichia coli or Salmonella spp. resistant to ceftriaxone. The study population included 54 finishing swine barns from three companies located in North Carolina. The barns were each classified according to their reported therapeutic ceftiofur use rates of "Rare," "Moderate," and "Common." Fecal samples from the barns were cultured for the presence of E. coli and Salmonella spp. resistant to ceftriaxone using selective media designed to recover rare organisms expressing the AmpC β-lactamase phenotype. A total of 1899 swine fecal samples yielded 1193 E. coli (63%) resistant to ceftriaxone. Recovery rates by ceftiofur use classification were 45% for Rare, 73% for Moderate, and 68% Common ceftiofur use groups. Barns reporting Rare ceftiofur use had a lower odds of recovery of E. coli (OR=0.32; p<0.001) resistant to ceftriaxone compared to Common use barns. The overall Salmonella spp. prevalence was 63.8% (n=714). Of these, 65 Salmonella were resistant to ceftriaxone with the highest rate (6%) found in the Common ceftiofur use group, followed by Rare (4.1%) and Moderate (0.15%). The odds of recovery of Salmonella resistant to ceftriaxone were similar for barns with ceftiofur use classified as Rare and Common. Samples from barns with ceftiofur use classified as Moderate had a lower odds (OR=0.02; p<0.01) of recovery of Salmonella resistant to ceftriaxone than barns classified as Common. Our result is consistent with the hypothesis that the use of ceftiofur in finishing swine barns, beyond its rare application, may influence the recovery of enteric E. coli with resistance to cephalosporin drugs, although other unmeasured factors appear to be important in the recovery of cephalosporin-resistant Salmonella. The dissemination of enteric bacteria with resistance to cephalosporins has the potential to impact both veterinary and human therapeutic treatment options.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Cephalosporin Resistance; Cephalosporins; Cross-Sectional Studies; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Feces; Humans; Logistic Models; Microbial Sensitivity Tests; North Carolina; Salmonella; Salmonella Infections, Animal; Swine; Swine Diseases

Topics: Aged; Anti-Bacterial Agents; Bile Duct Diseases; Ceftriaxone; Cholangiopancreatography, Magnetic Resonance; Diabetes Mellitus, Type 2; Diagnosis, Differential; Escherichia coli Infections; Hamartoma; Humans; Magnetic Resonance Imaging; Male; Tomography, X-Ray Computed; Ultrasonography

We describe a female patient with Alport disease who developed antiglomerular basement membrane nephritis late after kidney transplantation during the treatment of an acute bacterial pyelonephritis and discuss the potential role of the infection as a trigger for the development of this nephritis.

Topics: Adolescent; Anti-Bacterial Agents; Anti-Glomerular Basement Membrane Disease; Autoantibodies; Basement Membrane; Ceftriaxone; Drug Substitution; Escherichia coli Infections; Female; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Transplantation; Nephritis, Hereditary; Plasmapheresis; Pulse Therapy, Drug; Pyelonephritis; Treatment Outcome

Data from an 800-bed hospital showed an increase in the incidence density of ceftriaxone-resistant Escherichia coli, from 13.1 to 21.7 per 100 000 inpatient days over a 4-year period. Detailed testing performed on 54 E. coli isolates showed bla(CTX-M) extended-spectrum beta-lactamase (ESBL) genes (n = 37) and bla(CMY-like)ampC genes (n = 15). Typing data showed only limited clonal transmission in isolates with ESBL.

Topics: Aged; Anti-Bacterial Agents; Bacterial Typing Techniques; beta-Lactamases; Ceftriaxone; Cluster Analysis; DNA Fingerprinting; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Genotype; Hospitals, General; Humans; Male; Prevalence; Singapore

Intrauterine infection during pregnancy is associated with early activation of the fetal immune system and poor neurodevelopmental outcomes. Immune activation can lead to alterations in sensorimotor skills, changes in learning and memory and neural plasticity. Both interleukin-10 (IL-10) and Ceftriaxone have been shown to decrease immune system activation and increase memory capacity, respectively. Using a rodent model of intrauterine infection, we examined sensorimotor development in pups, learning and memory, via the Morris water maze, and long-term potentiation in adult rats. Pregnant rats at gestational day 17 were inoculated with 1 x 10(5) colony forming units of Escherichia coli (E. coli) or saline. Animals in the treatment group received IL-10/Ceftriaxone for 3 days following E. coli administration. Intrauterine infection delayed surface righting, negative geotaxis, startle response and eye opening. Treatment with IL-10/Ceftriaxone reduced the delay in these tests. Intrauterine infection impaired performance in the probe trial in the Morris water maze (saline 25.13+/-1.01; E. coli 20.75+/-1.01; E. coli+IL-10/Ceftriaxone 20.2+/-1.62) and reduced the induction of long-term potentiation (saline 141.5+/-4.3; E. coli 128.7+/-3.9; E. coli+IL-10/Ceftriaxone 140.0+/-10). In summary, the results of this study indicate that E. coli induced intrauterine infection delays sensorimotor and learning and memory, while IL-10/Ceftriaxone rescues some of these behaviors. These delays were also accompanied by an increase in interleukin-1beta levels, which indicates immune activation. IL-10/Ceftriaxone prevents these delays as well as decreases E. coli-induced interleukin-1beta activation and may offer a window of time in which suitable treatment could be administered.

Topics: Aging; Animals; Animals, Newborn; Anti-Bacterial Agents; Ceftriaxone; Escherichia coli Infections; Female; Hippocampus; Interleukin-10; Male; Maze Learning; Memory; Motor Activity; Nootropic Agents; Pregnancy; Pregnancy Complications, Infectious; Random Allocation; Rats; Rats, Sprague-Dawley; Space Perception; Treatment Outcome

Topics: Anti-Bacterial Agents; Ceftriaxone; Diabetic Nephropathies; Emphysema; Escherichia coli; Escherichia coli Infections; Female; Flank Pain; Humans; Middle Aged; Nephrostomy, Percutaneous; Oliguria; Pyelitis

Topics: Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Drug Resistance, Bacterial; Escherichia coli Infections; Humans; Male; Middle Aged; Upper Extremity Deep Vein Thrombosis

Myocarditis is defined clinically as inflammation of the heart muscle, which can be caused by infectious agents, toxins or immunologic reactions. Most recognized cases of acute myocarditis are secondary to cardiotropic viral infections. Escherichia coli rarely cause myocarditis. The authors report a 25-year-old woman with E coli-induced acute pyelonephritis and septic shock that was complicated with acute myocarditis. Her symptoms mimicked acute myocardial infarction. The authors discuss the possible mechanism of bacterial sepsis-induced myocarditis.

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Diagnosis, Differential; Electrocardiography; Escherichia coli Infections; False Positive Reactions; Female; Humans; Myocardial Infarction; Myocarditis; Pyelonephritis; Shock, Septic; Urinary Tract Infections

Zirconium molybdate gel was prepared by mixing (99)Mo, produced from (98)Mo(n,gamma) reaction and Zr solutions in nitrate media with excess H(2)O(2), and used as the base material for (99)Mo/(99m)Tc generator. The prepared generator showed a good performance. (99m)Tc eluted from the prepared generator passed the quality control tests with specifications meeting the requirements of European and US Pharmacopeias. The (99m)Tc eluate was used for labeling of cephalosporin analogue, ceftriaxone, which was then assessed for infection imaging in a mouse model. (99m)Tc-ceftriaxone was prepared at pH 9 with a radiochemical yield of 95+/-2% by adding (99m)Tc to 30 mg ceftriaxone in the presence of 50 microg SnCl(2).2H(2)O. Biodistribution studies in mice were carried out using experimentally induced infection in the left thigh using E. coli. Both thighs of the mice were dissected and counted to evaluate the ratio of bacterial infected thigh/contralateral thigh. (99m)Tc-ceftriaxone showed high uptake in the infectious lesion (T/NT =5.6+/-0.6 at 4h post injection). The abscess to normal muscle ratio indicated that (99m)Tc-ceftriaxone could be used for infection imaging. Besides, in vitro studies showed that (99m)Tc-ceftriaxone can differentiate between bacterial infection and sterile inflammation.

Topics: Animals; Bacterial Infections; Ceftriaxone; Escherichia coli Infections; Inflammation; Mice; Molybdenum; Muscle, Skeletal; Organotechnetium Compounds; Radionuclide Imaging; Technetium; Tissue Distribution; Zirconium

Multiresistant, extended spectrum beta lactamase (ESBL)-producing pathogens are an increasing problem in daily clinical life. This paper summarizes the development of resistance as well as epidemiology, diagnostics, and treatment of ESBL-producing micro-organisms. We analyzed microbiological data collected at the Grosshadern Clinic in Germany between 1996 and 2007, in order to assess the importance of these micro-organisms to medical practice and surgical care units.. Pathogens were isolated from 28,894 patients with Escherichia coli and 10,903 with Klebsiella pneumoniae pathogens between 1996 and 2006 and tested for ESBL production. For the year 2007 we have analyzed the complete spectrum of ESBL-producing pathogens and their distribution to different departments of the clinic. The agar diffusion test with five cephalosporins and an automated detection system (BD Phoenix) were used for screening purposes. Positive results were verified with the E- and double-disc agar diffusion tests.. The most important pathogens isolated from patients were E. coli and K. pneumoniae. Analysis of ESBL-producing E. coli pathogens from 1996 to 2006 showed the prevalence increasing from 0% to 4.1%. For ESBL-producing K. pneumoniae, we also found a prevalence rising from 0.3% in 1996 to 6.6% in 2006. For the year 2007 a further increase in ESBL-producing pathogens was detected, reaching 182 cases, with 118 of ESBL-producing E. coli (5.7 %) and 39 of ESBL-producing K. pneumoniae (7.4%). Of these, 24 cases with E. coli and nine with K. pneumoniae were surgery patients (20% and 23%, respectively).. The results show an increasing prevalence of ESBL-producing pathogens in hospitalized patients and in surgical departments. The resulting rise in treatment costs and patient risk require thorough knowledge of risk factors, therapy, and preventive measures.

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Cefotaxime; Ceftriaxone; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Europe; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Retrospective Studies; Risk Factors; Surgical Wound Infection

Topics: Aminoglycosides; Anti-Bacterial Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Bone Marrow; Ceftriaxone; Child; Chromosomes, Human, Pair 10; Cytarabine; Daunorubicin; Diagnosis, Differential; Escherichia coli Infections; Etoposide; Flow Cytometry; Gemtuzumab; Humans; Injections, Spinal; Leukemia, Myeloid, Acute; Male; Meningitis, Bacterial; Patient Transfer; Spinal Puncture; Trisomy

"Empty" liposomes and ceftriaxone (CT)-entrapped liposomes were developed. Lipids of natural origin, i. e. soybean phosphatidyl choline (PhCh) and cholesterol were used for the design. The conditions for production of the CT-entrapped liposomes were optimized to provide the maximum content of the antibiotic in the liposomes. The effect of the "empty" liposomes and the antibiotic-entrapped liposomes on healing of skin wounds was studied on rats. The wound on the skin surface of the rat back was purulent due to contamination with E. coli (10(9) cells/ml). The treatment with the antibiotic solution, "empty" liposomes or CT-entrapped liposomes was started in 48 hours. The use of the PhCh "empty" liposomes promoted more rapid healing of the wound vs. the control or the treatment with CT aqueous solution. The treatmen of the wound with the CT-entrapped PhCh liposomes provided 2 times more rapid healing vs. the control or the use of the CT aqueous solution.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Liposomes; Rats; Skin; Wound Healing; Wound Infection; Wounds, Penetrating

Urinary tract infections (UTI) are among the most prevalent infectious diseases, and their financial burden on society is substantial. Management of UTIs has been complicated by the emergence of resistance to most commonly used antibiotics. Increasing prevalence of resistance has led to a gradual evolution in the antibiotics used to treat UTIs. The aims of this study were to determine the TMP/SMX (trimethoprim/sulfamethoxazole) resistance rate in patients with uncomplicated UTIs and to determine which empiric antibiotics are prescribed in the emergency department for the outpatient management of UTI. Between June 2004 and May 2005, archives of the emergency department were searched retrospectively and the files of patients diagnosed with UTI were reviewed. Patients' demographical data, urine culture results, pathogen microorganisms, and TMP/SMX and fluoroquinolone (FQ) resistance rates were recorded. We obtained information from 274 files of patients who had been diagnosed with UTI. The most frequently isolated pathogen was Escherichia coli (54%). Of the 274 patients diagnosed with UTI, 251 had been started on empiric antibiotics. The most frequently prescribed antibiotics were FQs (85%), and the first choice in this group was ofloxacin (58%). The resistance rate for TMP/SMX was 34% and all of the resistant microorganisms were E. coli. The resistance rate for the FQ group was 16.4% and resistant microorganisms were E. coli. In the treatment of UTIs in our patient population, the most prescribed antibiotics were FQs. At the same time it was found that resistance rates against FQ antibiotics are as high as 16.4%. Unfortunately, in our population, in the near future, empiric FQ use may result in bacterial resistance.

Topics: Adolescent; Adult; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Aza Compounds; Ceftriaxone; Drug Resistance, Microbial; Escherichia coli Infections; Female; Fluoroquinolones; Humans; Male; Middle Aged; Moxifloxacin; Quinolines; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections; Young Adult

The pathophysiology of sepsis is due in part to early systemic inflammation. Here we describe molecular and cellular responses, as well as survival, in A 2A adenosine receptor (AR) agonist treated and untreated animals during experimental sepsis.. Sepsis was induced in mice by intraperitoneal inoculation of live bacteria (Escherichia coli or Staphylococcus aureus) or lipopolysaccharide (LPS). Mice inoculated with live bacteria were treated with an A 2A AR agonist (ATL313) or phosphate buffered saline (PBS), with or without the addition of a dose of ceftriaxone. LPS inoculated mice were treated with ATL313 or PBS. Serum cytokines and chemokines were measured sequentially at 1, 2, 4, 8, and 24 hours after LPS was administered. In survival studies, mice were followed until death or for 7 days.. There was a significant survival benefit in mice infected with live E. coli (100% vs. 20%, p = 0.013) or S. aureus (60% vs. 20%, p = 0.02) when treated with ATL313 in conjunction with an antibiotic versus antibiotic alone. ATL313 also improved survival from endotoxic shock when compared to PBS treatment (90% vs. 40%, p = 0.005). The serum concentrations of TNF-alpha, MIP-1 alpha, MCP-1, IFN-gamma, and IL-17 were decreased by ATL313 after LPS injection (p < 0.05). Additionally, ATL313 increased the concentration of IL-10 under the same conditions (p < 0.05). Circulating white blood cell concentrations were higher in ATL313 treated animals (p < 0.01).. Further studies are warranted to determine the clinical utility of ATL313 as a novel treatment for sepsis.

Topics: Animals; Anti-Inflammatory Agents; Ceftriaxone; Cytokines; Disease Models, Animal; Escherichia coli Infections; Female; Inflammation; Leukocytes; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Piperidines; Receptor, Adenosine A2A; Sepsis; Staphylococcal Infections; Survival Analysis

The need to limit unnecessary antibiotic treatments and recent studies with unusual antibiotics in pediatrics (fluoroquinolones) or in digestive tract infections (azithromycin) have led to update the treatment of acute gastro-enteritis. In 2007, the European Society for Pediatric Infectious Diseases and the European Society for Gastroenterology Hepatology and Nutrition have issued guidelines. The proven shigellosis as well as the strong suspicion have to be treated promptly with antibiotics, mainly azithromycin. There is no argument to treat moderate salmonella gastroenteritis or carriage. However, the severe cases and those occurring in high risk patient must be treated (ciprofloxacin or ceftriaxone). It is recommended to treat diarrhoea due to Campylobacter jejuni in case of early diagnosis. The presumptive antibiotic treatment should be limited but can not be dismissed, in invasive cases gastro-enteritis, especially in traveller children.

Topics: Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Campylobacter Infections; Campylobacter jejuni; Ceftriaxone; Child; Ciprofloxacin; Diarrhea; Dysentery, Bacillary; Escherichia coli Infections; Gastroenteritis; Humans; Salmonella Infections

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Combined Modality Therapy; Endocarditis, Bacterial; Escherichia coli Infections; Female; Gastroenteritis; Gentamicins; Heart Valve Prosthesis Implantation; Humans; Imipenem; Middle Aged; Urinary Tract Infections

Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhotic patients associated with a high mortality.. To develop an available experimental model of induced bacterial peritonitis in cirrhosis.. Sprague-Dawley rats with carbon-tetrachloride-induced cirrhosis with (N=22) or without (N=101) ascites were randomized to receive an intraperitoneal administration of different concentrations of Escherichia coli (E. coli) diluted in 1 mL of sterile water in ascitic rats and in different volumes in nonascitic rats. A subgroup of nonascitic animals received ceftriaxone 4 h after E. coli inoculation. Mortality of rats was evaluated 24 h after bacterial inoculation.. None of the rats receiving sterile water alone and only one infected with 10(7) cfu of E. coli died. Ascitic rats showed a lower mortality rate than nonascitic rats infected with 10(8) or 10(9) cfu of E. coli (P<0.05). Mortality was higher with 10(9) cfu than with 10(8) cfu of E. coli in ascitic (P NS) and nonascitic (P<0.01) rats. A trend was noted to ward higher mortality in nonascitic rats inoculated with 10(8) cfu with increasing water volumes. A marked peritoneal polymorphonuclear cell response was observed 4 h after E. coli injection in both ascitic and nonascitic rats. Antibiotic therapy significantly reduced the mortality rate of rats infected with 10(8) cfu (P<0.01).. This experimental model of induced bacterial peritonitis in cirrhosis with or without ascites may represent a useful tool for the study of pathogenic events postinfection and for the design of new therapeutic strategies to treat patients with SBP.

Topics: Animals; Anti-Bacterial Agents; Ascites; Bacterial Infections; Carbon Tetrachloride; Ceftriaxone; Disease Models, Animal; Escherichia coli Infections; Liver Cirrhosis, Experimental; Male; Peritonitis; Random Allocation; Rats; Rats, Sprague-Dawley

To examine the incidence, risk factors, microbial pathogens, and pregnancy outcomes of pregnant women with acute antepartum pyelonephritis.. Among all pregnant women admitted to Patan Hospital, Nepal from 14 April 2004 to 13 April 2005, pregnant women with acute pyelonephritis were retrospectively studied. Furthermore, the pregnancy outcomes of these women were compared with those of the general obstetric population received at our hospital during the same time period.. Of 7034 pregnant women delivered at our hospital, 94 cases of acute antepartum pyelonephritis were diagnosed during the study period (incidence: 1.3%). Maternal mean age for the infection was 22 +/- 3.41 years. Acute pyelonephritis was most frequently occurred in nulliparous women (75%), and in the second trimester (60%). Of 94 cases, 62 (65.95%) showed positive urine culture, with the predominating organism Escherichia coli in 81% (50 of 62) of cases. E. coli was found most sensitive to nitrofurantoin (82.1% of cases), followed by ceftriaxone (81.55% of cases), gentamicin (77.01% of cases), ofloxacin (60.57% of cases), and ciprofloxacin (59% of cases). The incidences of low-birthweight babies (14%) and preterm babies (7.81%) in the cases with acute antepartum pyelonephritis were not significantly different compared to that of all births in our hospital during the same period (13% and 8%, respectively; P > 0.05).. Acute pyelonephritis requiring admission to hospital most frequently occurs in nulliparous women, and in the second trimester. The predominating organism responsible for acute pyelonephritis is E. coli. Ceftriaxone, because of its safety and negligible side-effect, should be the drug of choice for acute antepartum pyelonephritis.

Topics: Acute Disease; Adult; Anti-Bacterial Agents; Ceftriaxone; Escherichia coli Infections; Female; Humans; Incidence; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Length of Stay; Nepal; Parity; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Pregnancy Outcome; Pregnancy Trimester, Second; Pyelonephritis; Retrospective Studies; Risk Factors

Emphysematous pyelonephritis is characterized by infection and gas formation in the renal parenchyma. This rare disorder tends to occur more frequently in patients with diabetes mellitus and urinary tract obstruction. In this case report, we describe a nondiabetic patient with Hinman syndrome who developed recurrent emphysematous pyelonephritis that was successfully treated with antibiotics on both occasions.

Topics: Anti-Bacterial Agents; Ceftriaxone; Emphysema; Escherichia coli Infections; Humans; Male; Middle Aged; Pyelonephritis; Recurrence; Remission Induction

Effective methods to control the emergence of extended-spectrum beta -lactamase-producing Escherichia coli and Klebsiella species (ESBL-EK) remain unclear. Variations in the patient populations at different hospitals may influence the effect of antimicrobial formulary interventions.. To examine variations across hospitals in the response to antimicrobial interventions (ie, restriction of ceftazidime and ceftriaxone) designed to curb the spread of ESBL-EK, we conducted a 5-year quasi-experimental study. This study was conducted at 2 hospitals within the same health system: Hospital A is a 625-bed academic medical center, and Hospital B is a 344-bed urban community hospital. All adult patients with a healthcare-acquired clinical culture of ESBL-EK from July 1, 1997 through December 31, 2002 were included.. After the interventions, the use of ceftriaxone decreased by 86% at Hospital A and by 95% at Hospital B, whereas the use of ceftazidime decreased by 95% at Hospital A and by 97% at Hospital B. The prevalence of ESBL-EK at Hospital A decreased by 45% (P < .001), compared with a 22% decrease at Hospital B (P = .36). The following variables were significantly more common among ESBL-EK-infected patients at Hospital B: residence in a long-term care facility (adjusted odds ratio, 3.77 [95% confidence interval, 1.70-8.37]), advanced age (adjusted odds ratio, 1.04 [95% confidence interval, 1.01-1.06]), and presence of a decubitus ulcer (adjusted odds ratio, 4.13 [95% confidence interval, 1.97-8.65]).. The effect of antimicrobial formulary interventions intended to curb emergence of ESBL-EK may differ substantially across institutions, perhaps as a result of differences in patient populations. Variability in the epidemiological profiles of ESBL-EK isolates at different hospitals must be considered when designing interventions to respond to these pathogens.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Ceftazidime; Ceftriaxone; Enterobacteriaceae; Escherichia coli Infections; Formularies, Hospital as Topic; Humans; Klebsiella Infections; Middle Aged; Population Groups

Within 10 days after cystoscopy causing urosepsis this patient developed persistant neckpain as initial symptom of vertebral osteomyelitis. E. coli was isolated from urine, blood cultures and later from bone biopsy. Antibiotic treatment did not stop the progress of the disease. A transverse spinal cord syndrome occurred due to a pathological fracture of C5 and C6 and operative decompression was necessary. The rapid onset of osteomyelitis was impressive. For effective treatment of bacterial osteomyelitis a bone biopsy is sometimes unavoidable and indicated.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cervical Vertebrae; Cystoscopy; Escherichia coli Infections; Humans; Male; Middle Aged; Osteomyelitis; Sepsis

Topics: Acute Disease; Anti-Bacterial Agents; Ceftriaxone; Child; Escherichia coli Infections; Humans; Kidney; Kidney Calculi; Male; Pyelonephritis; Ultrasonography

Deliberate induction of hypercapnic acidosis protects against lung injury after ischemia-reperfusion, endotoxin-induced, and ventilation-induced lung injury. The efficacy of hypercapnic acidosis in bacterial lung infection, a common cause of acute respiratory distress syndrome, is not known. Furthermore, its effect may differ depending on the presence or absence of antibiotic therapy. We investigated whether hypercapnic acidosis-induced by adding CO2 to inspired gas-would protect against acute lung injury induced by pulmonary Escherichia coli instillation in an in vivo model in the presence and absence of effective antibiotic therapy.. Prospective randomized animal study.. University research laboratory.. Adult male Wistar-Kyoto rats.. The animals were anesthetized and ventilated. In series 1, rats were administered intravenous ceftriaxone (100 mg x kg) and randomized to normocapnia (Normocapnia-ABx; Fico2 0.00, n = 10) or hypercapnia (Hypercapnia-ABx; Fico2 0.05, n = 10) groups. E. coli (8.4 x 10 colony forming units) was instilled intratracheally. Series 2 animals did not receive antibiotics. They were randomized to normocapnia (Normocapnia, n = 10) or hypercapnia (Hypercapnia, n = 10) groups, and intratracheal E. coli was administered. All animals were ventilated for 6 hrs.. In series 1, there were no differences between Hypercapnia-ABx and Normocapnia-ABx groups with regard to: (a-a)o2 gradient (mean +/- sem; 215 +/- 13 vs. 252 +/- 22 mm Hg), Pao2, bronchoalveolar lavage neutrophil count, static lung compliance, or histologic injury. Lung bacterial yield was not different between the groups. In series 2, in the absence of antibiotic therapy, there were no differences between Hypercapnia and Normocapnia groups in: (a-a)o2 gradient (mean +/- sem, 345 +/- 25 vs. 332 +/- 23 mm Hg), systemic Pao2, bronchoalveolar lavage neutrophil count, or static lung compliance. Lung bacterial yield was not altered by hypercapnia in either series 1 or 2.. We conclude that hypercapnic acidosis did not alter the magnitude of the lung injury induced by intratracheal E. coli instillation in the presence or absence of antibiotics.

Topics: Acidosis, Respiratory; Animals; Ceftriaxone; Escherichia coli Infections; Hypercapnia; Male; Pneumonia, Bacterial; Rats; Rats, Inbred WKY; Respiratory Distress Syndrome; Severity of Illness Index

The evolution and the relationship between inflammatory and renal-injury markers in women with acute uncomplicated pyelonephritis under antimicrobial therapy were investigated in a prospective study. Markers were measured before and 6 and 24 h after the intravenous administration of 1 g of ceftriaxone. Before treatment, the median levels of all markers except the serum creatinine levels were high. Twenty-four hours after the onset of antibiotic treatment, the C-reactive protein (CRP) level continued to be high, while the serum interleukin-6 (IL-6) levels and the urine IL-6, IL-8, albumin, and immunoglobulin G (IgG) levels decreased significantly. In contrast, serum creatinine and tumor necrosis factor alpha levels and urine N-acetyl-beta-glucosaminidase, alpha1-microglobulin, and beta2-microglobulin levels did not change over time. There was a significant correlation between IL-6 and IL-8 levels and urine albumin and IgG levels (urine albumin and IgG levels are glomerular and urinary tract-injury markers) as well as between serum CRP levels and the levels of the tubular-injury markers. In women with acute pyelonephritis, appropriate antibiotic treatment rapidly decreases serum IL-6 levels and urine IL-6 and IL-8 levels, which correlate well with urine albumin and IgG levels.

Topics: Acute Disease; Adult; Aged; Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Ceftriaxone; Escherichia coli Infections; Female; Humans; Immunoglobulin G; Inflammation Mediators; Interleukin-6; Interleukin-8; Kidney; Middle Aged; Prospective Studies; Pyelonephritis

To evaluate the effects of maternal antibiotic treatment on fetal brain cell death in a rabbit intrauterine infection model.. After Escherichia coli uterine-horn inoculation in 22 pregnant rabbits, followed at various times by ceftriaxone and caesarean section, cell death in white matter (histology and fragmented DNA staining) from fetuses killed at extraction was compared across groups using the Mantel-Haenszel test and Fisher's exact test for small numbers.. White matter cell death was consistently present at 48 h, with ceftriaxone initiation at 24 h (group 1), detectable at 84 but not 60 h, with ceftriaxone initiation at 12 h, and significantly reduced at 84 h with ceftriaxone initiation at 6 h (60% vs 100% in group 1, p < 0.001, Fisher's exact test).. Early maternal antibiotic therapy delays white matter cell death in rabbit fetuses exposed to intrauterine infection. This may provide a window for preventing white matter damage.

Topics: Animals; Anti-Bacterial Agents; Brain; Ceftriaxone; Cell Death; Cerebral Ventricles; Escherichia coli Infections; Female; In Situ Nick-End Labeling; Injections, Intravenous; Pregnancy; Rabbits

The effect of optimized maternal therapy by bactericidal agents was evaluated in a reproducible rabbit model of Escherichia coli maternofetal infection simulating human pharmacokinetics. Intravenous antibiotic therapy was begun in the pregnant rabbit 12 h after bacterial intrauterine inoculation, using a computer-controlled pump to simulate human pharmacokinetics of ceftriaxone (1 g/day) associated or not with gentamicin (3 mg/kg of body weight/day). Data were compared for fetal survival, quantitative blood cultures, fetal histology in treated versus untreated groups, and maternal and fetal antibiotic concentrations in plasma in treated animals. Antibiotic therapy led to dramatic improvement in maternal outcome (100% survival versus 100% death in the untreated group in association with maternal septicemia). Fetal survival also improved, with the two-drug combination providing a more potent effect. After 3 days of treatment, 32% of fetuses survived with one-drug therapy and 62% with two-drug therapy (Yates corrected chi(2), P < 0.05). In untreated animals, bacterial counts in blood cultures increased rapidly during the first 24 h up to 8.1 +/- 0.5 log CFU/ml, but remained relatively constant at all times with antibiotic treatment: 4.5 +/- 0.7 log CFU/ml at the start of treatment and 6.2 +/- 0.4 and 5.2 +/- 0.9 log CFU/ml after 72 h for one- and two-drug therapy, respectively (data are means +/- standard deviations). The failure of animals to be cured after 3 days of treatment was not due to an inadequate concentration of ceftriaxone, as the residual level in fetal serum at sacrifice was more than 1000 times the MIC of the microbe. Unexpectedly, inflammation in fetal lung decreased in the treated group after as little as 24 h of antibiotic therapy, despite persistent bacteremia. Although maternal outcome improved and drug concentrations were above the MIC, the treatment did not achieve sterilization of fetuses in utero for this rabbit E. coli maternofetal infection. However, fetal survival showed some improvement, and the histologic features of lung inflammation were reduced.

Topics: Animals; Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Female; Fetal Diseases; Infectious Disease Transmission, Vertical; Maternal-Fetal Exchange; Pregnancy; Rabbits

To investigate the effect of granulocyte colony-stimulating factor (G-CSF) in the treatment of Escherichia coli peritonitis with and without ceftriaxone in a nonneutropenic rat model.. The rats were divided into five groups: control group (C) receiving physiological saline; peritonitis group (P) infected intraperitoneally with a live bacterial suspension of E. coli; peritonitis and antibiotic group (PA) receiving ceftriaxone 3 h after being infected; peritonitis, antibiotic, and G-CSF group (PAG) receiving G-CSF and antibiotic 3 h after infection; and peritonitis and G-CSF group (PG).. All rats in group C survived. Any animals which did not survive died within 24h after inoculation. A significantly higher rate of survival, 95%, was observed with antibiotic treatment alone (PA), in comparison to the G-CSF-treated groups, PAG and PG, 52% and 57%, respectively.. No beneficial effect of G-CSF treatment was seen in the E. coli peritonitis and antibiotic therapy remains the basic treatment for this disease.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Escherichia coli Infections; Granulocyte Colony-Stimulating Factor; Leukocyte Count; Male; Neutrophils; Peritonitis; Rats; Survival Rate

Topics: Accidental Falls; Aged; Aged, 80 and over; Amoxicillin; Anti-Bacterial Agents; Back Pain; Bacteremia; Ceftriaxone; Cephalosporins; Diagnosis, Differential; Discitis; Drug Therapy, Combination; Escherichia coli Infections; Gentamicins; Humans; Lumbar Vertebrae; Male; Penicillins

We examined all ceftriaxone-resistant Escherichia coli isolates obtained from clinical samples during 16 months (1 Dec. '97-31 Mar. '99). A total of 97 resistant isolates from 36 patients were obtained, mostly from urine specimens. Of these patients, 35/36 were over 75 years old, most lived in nursing homes, were dependent on nursing in their daily lives, and were incontinent and/or had indwelling catheters. All 97 isolates had similar susceptibility profiles: resistant to ciprofloxacin, gentamicin, ampicillin, amoxycillin/clavulanate, tricarcillin/clavulanate, aztreonam, and cefuroxime; decreased susceptibility to ceftazidime and cefepime; and susceptible to imipenem and meropenem. Double-disc tests indicated that all strains produced extended spectrum beta-lactamase(s). All the isolates belonged to 1 of 3 E. coli serotypes: 79 were 0153:H31, 13 were 0142:H10, and 5 were 0102:H6.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Ceftriaxone; Cephalosporin Resistance; Escherichia coli; Escherichia coli Infections; Humans; Male; Microbial Sensitivity Tests; Serotyping

Topics: Ceftriaxone; Cephalosporins; Child; Cholelithiasis; Escherichia coli Infections; Female; Humans; Pyelonephritis; Risk Factors; Time Factors

Forty patients with spontaneous bacterial peritonitis, three of whom had complicating acute hepatitis syndrome, eight late-onset hepatic failure, and 29 with cirrhosis, were treated with ceftriaxone 2 g intravenously once daily for 5 days. Ascitic fluid culture was positive in 28 patients, with Escherichia coli and Klebsiella as common isolates. All the bacteria isolated were sensitive to ceftriaxone except Enterococcus faecalis, which was isolated in a cirrhotic patient. All culture-positive patients sensitive to ceftriaxone showed bacteriological cure and 26 (65%) patients showed cytological cure after 48 hours of treatment. A total of 95% were cured of their infection after 5 days of treatment. Twelve (30%) patients died during hospitalisation after documented cure of their spontaneous bacterial peritonitis (renal failure, gastrointestinal bleed and cerebral oedema were the primary causes of death). Infection-related mortality due to Pseudomonas septicaemia was seen in one cirrhotic patient.

Topics: Adolescent; Adult; Ceftriaxone; Cephalosporins; Escherichia coli Infections; Female; Humans; Klebsiella Infections; Liver Diseases; Male; Middle Aged; Peritonitis; Prospective Studies

E. coli meningitis is a disease that occurs in predisposed patients, either as a result of trauma or in neonates after neurosurgery. Recurrent E. coli meningitis in an adult without any apparent predisposition is uncommon, and hydrocephalus complicating bacterial meningitis is even more rare. We report a unique case of a 67-year-old alcoholic man who had had 2 consecutive episodes of E. coli meningitis within 2 months. In both episodes there was a favorable response to ceftriaxone. However, normotensive hydrocephalus appeared a few weeks later, with mental and physical deterioration.

Topics: Aged; Alcoholism; Ceftriaxone; Cephalosporins; Escherichia coli Infections; Humans; Hydrocephalus, Normal Pressure; Male; Meningitis, Bacterial; Recurrence; Tomography, X-Ray Computed

To compare a recombinant bactericidal/permeability-increasing protein variant and a recombinant endotoxin-neutralizing protein.. Randomized, blinded, controlled study, using a rat model of sepsis.. Animal research facility.. Male Wistar rats.. An inoculum of 1.5 x 10(7) to 1.8 x 10(8) Escherichia coli O18ac K1, implanted in the peritoneum, produced bacteremia in 95% of animals after 1 hr. One hour after E. coli challenge, animals received recombinant bactericidal/permeability-increasing protein variant, recombinant endotoxin-neutralizing protein, or saline intravenously, followed by ceftriaxone and gentamicin intramuscularly.. Twenty-four (85.7%) of 28 animals receiving recombinant endotoxin-neutralizing protein (p < .001 vs. control) survived 7 days compared with nine (33.3%) of 27 recombinant bactericidal/permeability-increasing protein variant-treated (p < .001 vs. control) and two (6.5%) of 31 control animals.. Both recombinant endotoxin-neutralizing protein and recombinant bactericidal/permeability-increasing protein variant improved survival. Recombinant endotoxin-neutralizing protein was superior to recombinant bactericidal/permeability-increasing protein variant in its protective effect at the doses tested. Our results suggest that both proteins may be useful in the treatment of human Gram-negative sepsis.

Topics: Animals; Anti-Infective Agents; Ceftriaxone; Disease Models, Animal; Drug Therapy, Combination; Escherichia coli Infections; Gentamicins; Gram-Negative Bacterial Infections; Male; Rats; Rats, Wistar; Recombinant Proteins; Sepsis; Survival Analysis

Topics: Ascitic Fluid; Bacterial Infections; Ceftriaxone; Cephalosporins; Empyema, Pleural; Escherichia coli Infections; Female; Hepatitis C; Humans; Liver Cirrhosis; Middle Aged

Intra-abdominal abscess is seldom adequately treated by systemic antibiotics alone and often requires surgical or computed tomography-guided drainage for resolution. Abscess penetration of six currently used antibiotics was examined in a murine intra-abdominal abscess model. Ampicillin/sulbactam, cefmetazole, clindamycin, and trospectomycin penetrated intra-abdominal abscesses to a greater degree than cefoxitin and ceftriaxone. Abscess pus antibiotic levels were not significantly higher after multiple doses than after a single dose. Pus antibiotic levels below the MIC90 for Bacteroides and E. coli within intra-abdominal abscess were observed for most antibiotics with the doses used in this study. Selection of antibiotics with a greater ability to penetrate abscess may be important in optimally treating patients with abdominal infection.

Topics: Abdominal Abscess; Ampicillin; Animals; Anti-Bacterial Agents; Bacteroides fragilis; Bacteroides Infections; Cefmetazole; Cefoxitin; Ceftriaxone; Clindamycin; Drug Evaluation, Preclinical; Drug Therapy, Combination; Escherichia coli Infections; Hydrogen-Ion Concentration; Male; Mice; Microbial Sensitivity Tests; Spectinomycin; Sulbactam

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

Treatment of fecal peritonitis includes administration of antibiotics, physical removal of contaminants, and restoration of gastrointestinal integrity. The temporal relationship of parenteral antibiotics and peritoneal irrigation with varied antibiotic solutions was studied in a peritonitis model. Antibiotics in high concentrations may actually inhibit host immune cells; therefore, dilute solutions used were MIC (minimum inhibitory concentration) (micrograms per millimeter) equivalent to usually achieved standard therapeutic blood levels. Sprague-Dawley rats were given a quantitative intraperitoneal challenge of 2 x 10(10) CFU/kg Escherichia coli and 10 mg autoclaved rat feces. Rats were randomized to receive 30 mg/kg intramuscular ceftriaxone (CTRX) either at the time of challenge (T = 0) or 2 hr later (T = 2). Two hours after peritonitis, rats received peritoneal irrigation with 30 cc of (1) normal saline, (2) dilute (10 mg/liter) CTRX solution, or (3) concentrated (1000 mg/liter) CTRX solution or (4) no irrigation. Survival and intraperitoneal pathology were then assessed. Parenteral CTRX given concurrently with peritoneal contamination improved survival (67%) compared with parenteral administration given 2 hr later (33%) (P < 0.05). Intraperitoneal CTRX irrigation improved survival (100%) in animals that received parenteral CTRX concurrently with contamination; this beneficial effect was present with both dilute and concentrated solutions and was significantly better than saline irrigation alone. Parenteral antibiotics given early after contamination of the peritoneum associated later with peritoneal lavage with antibiotic solutions improved survival.

Topics: Abscess; Animals; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Feces; Injections, Intramuscular; Male; Peritoneal Diseases; Peritoneal Lavage; Peritonitis; Random Allocation; Rats; Rats, Sprague-Dawley

Escherichia coli and Staphylococcus aureus are the most common pathogens encountered in septic shock. This is a descriptive study in which the pathophysiologic response to infusions of LD100 concentrations of E. coli and S. aureus are staged and compared. Equivalent concentrations of both organisms were infused over a 2 hr period into antibiotic-treated and untreated animals with the following results: 1) The apparent clearance of E. coli was less than that of S. aureus over the 2-hr infusion period, but far greater during the next 8 hr in both antibiotic-treated and untreated animals. Thus the clearance of E. coli fits a one-compartment (intravascular), and that of S. aureus fits a two-compartment (intra- and extravascular) model. 2) The intensity of the cardiovascular, temperature, and metabolic response to E. coli was greater, whereas that of the disseminated intravascular coagulant (DIC) response to S. aureus was greater. We conclude, therefore, that the response to E. coli consists of four stages with no invasion and colonization of tissues, whereas the response to S. aureus consists of two stages with invasion and colonization of tissues.

Topics: Animals; Ceftriaxone; Disease Models, Animal; Escherichia coli Infections; Gentamicins; Hemodynamics; Hemostasis; Kidney; Lung; Papio; Shock, Septic; Staphylococcal Infections

The purpose of this study was to determine ceftriaxone (CTX) pharmacokinetics during pregnancy. Six women (26 to 34 years of age) admitted for chorioamnionitis (n = 4) or pyelonephritis (n = 2) were included. Gestational age ranged from 29 1/7 to 40 5/7 weeks. Initial intravenous treatment was ceftriaxone (CTX) (2 g/d), tobramycin (3 mg/kd/d) and ornidazole (1 g/d). Blood specimens were collected during the first treatment day (D1) to determine the primary pharmacokinetic profile of CTX then at steady-state (D7) to look for systemic accumulation. In two patients, transplacental passage of CTX was evaluated by determining the ratio of fetal and maternal concentrations (F/M) at delivery. Plasma CTX levels were determined using high-performance liquid chromatography. A noncompartmental method was used for pharmacokinetic analysis. Each patient served as her own control. Data obtained on D1 and D7 were compared using Wilcoxon's test (values of p < or = 0.05 were considered significant). A group of healthy controls given a similar regimen was also used. 1) Tolerance was outstanding, recovery was achieved in every case, and there were no premature deliveries. 2) No evidence of accumulation of CTX was found and kinetic profiles on D1 and D7 were not significantly different. 3) Mean kinetic parameter values were closely similar to those found in healthy volunteers. 4) Residual levels of total CTX and free CTX determined after 24 hours were greater than the minimal inhibitory concentration (MICs) of susceptible organisms. 5) The usual recommended dosage of CTX (2 g/d) proved adequate during the third trimester of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Ceftriaxone; Chorioamnionitis; Drug Therapy, Combination; Escherichia coli Infections; Female; Humans; Placenta; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Third; Proteus Infections; Pseudomonas Infections

To study postpartum distribution and protein binding of ceftriaxone (CTX) between maternal blood and milk and to discuss risk factors and possible impact for the neonate.. Reference articles and books are identified in the text.. CTX distribution and protein binding between maternal blood and milk postpartum were studied in a patient at term presenting with acute pyelonephritis caused by Escherichia coli. The antibiotic therapy prescribed pending bacteriology results consisted of CTX 2 g/d, ornidazole 1 g/d, and tobramycin 3 mg/kg/d. Pharmacokinetics of total CTX were studied after the first 2-g infusion. At plateau (i.e., two days after delivery; seventh infusion), pharmacokinetics and milk distribution of total and free CTX also were studied. No accumulation of CTX was noted in the plasma at plateau. When high dosages of CTX are used (approximately 2 g), its penetration into the milk is important (i.e., protein binding capacity is overwhelmed). No notable adverse reactions occurred in mother or child. Thus, an important diffusion into the milk (4.4 percent of the dose) appears not to be clinically important. Our knowledge of both metabolism and milk distribution of drugs with high protein binding (> or = 95 percent) and an acid characteristic should be expanded to better understand their use during both the pregnancy and postpartum periods. Finally, the child of the patient described here has normal initial growth and development at the present time.. Caution should be taken when drugs such as CTX, which have both high protein binding (> or = 95 percent) and an acid characteristic are administered to breastfeeding women. Drugs of this type should be systematically investigated to better understand their use during pregnancy and postpartum.

Topics: Adult; Blood Proteins; Ceftriaxone; Escherichia coli Infections; Female; France; Humans; Infant, Newborn; Male; Milk, Human; Postpartum Period; Pregnancy; Pregnancy Complications, Infectious; Protein Binding; Pyelonephritis; Risk Factors

To determine the outcome of outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone.. Prospective consecutive cohort study.. Urban emergency department.. Five hundred three infants 28 to 89 days of age with temperatures greater than or equal to 38 degrees C who did not appear ill, had no source of fever detected on physical examination, had a peripheral leukocyte count less than 20 x 10(9) cells/L, had a cerebrospinal fluid leukocyte count less than 10 x 10(6)/L, did not have measurable urinary leukocyte esterase, and had a caretaker available by telephone. Follow-up was obtained for all but one patient (99.8%).. After blood, urine, and cerebrospinal fluid cultures had been obtained, the infants received 50 mg/kg intramuscularly administered ceftriaxone and were discharged home. The infants returned for evaluation and further intramuscular administration of ceftriaxone 24 hours later; telephone follow-up was conducted 2 and 7 days later.. Twenty-seven patients (5.4%) had a serious bacterial infection identified during follow-up; 476 (94.6%) did not. Of the 27 infants with serious bacterial infections, 9 (1.8%) had bacteremia (8 of these had occult bacteremia and 1 had bacteremia with a urinary tract infection), 8 (1.6%) had urinary tract infections without bacteremia, and 10 (2.0%) had bacterial gastroenteritis without bacteremia. Clinical screening criteria did not enable discrimination between infants with and those without serious bacterial infections. All infants with serious bacterial infections received an appropriate course of antimicrobial therapy and were well at follow-up. One infant had osteomyelitis diagnosed 1 week after entry into the study, received an appropriate course of intravenous antimicrobial therapy, and recovered fully.. After a full evaluation for sepsis, outpatient treatment of febrile infants with intramuscular administration of ceftriaxone pending culture results and adherence to a strict follow-up protocol is a successful alternative to hospital admission.

Topics: Ambulatory Care; Bacteremia; Bacteria; Bacterial Infections; Ceftriaxone; Escherichia coli Infections; Feces; Female; Fever; Follow-Up Studies; Gastroenteritis; Hospitalization; Humans; Infant; Injections, Intramuscular; Male; Treatment Outcome; Urinary Tract Infections

The murine immune response to Escherichia coli exposed to subminimal inhibitory concentrations of four antibiotics was investigated. Groups of mice were injected for 8 weeks with formalin-killed bacteria and subsequently challenged with 10 x LD50 of viable E. coli. Mice receiving saline only (controls) died within 24 h. The mortality of mice immunized with ciprofloxacin-treated E. coli was significantly lower than that of mice immunized with E. coli untreated or treated with other antibiotics. Sera from mice immunized with ciprofloxacin-treated bacteria showed better bacteriostatic capacity and enhanced production of antibodies that bound to homologous and heterologous lipopolysaccharide isolated from several smooth and rough gram-negative strains. The better protection observed in mice immunized with ciprofloxacin-treated E. coli was probably due to an enhanced production of antibodies to epitopes on lipopolysaccharide that became better exposed and so more accessible after treatment with ciprofloxacin.

Topics: Animals; Anti-Bacterial Agents; Aztreonam; Blood Bactericidal Activity; Ceftriaxone; Ciprofloxacin; Complement System Proteins; Enzyme-Linked Immunosorbent Assay; Epitopes; Escherichia coli; Escherichia coli Infections; Female; Immunization; Immunoglobulin G; Immunoglobulin M; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Netilmicin; Opsonin Proteins; Phagocytosis

We evaluated the pharmacokinetics and therapeutic efficacy of ampicillin combined with sulbactam in a rabbit model of meningitis due to a beta-lactamase-producing strain of Escherichia coli K-1. Ceftriaxone was used as a comparison drug. The MIC and MBC were 32 and greater than 64 micrograms/ml (ampicillin), greater than 256 and greater than 256 micrograms/ml (sulbactam), 2.0 and 4.0 micrograms/ml (ampicillin-sulbactam [2:1 ratio, ampicillin concentration]) and 0.125 and 0.25 micrograms/ml (ceftriaxone). All antibiotics were given by intravenous bolus injection in a number of dosing regimens. Ampicillin and sulbactam achieved high concentrations in cerebrospinal fluid (CSF) with higher dose regimens, but only moderate bactericidal activity compared with that of ceftriaxone was obtained. CSF bacterial titers were reduced by 0.6 +/- 0.3 log10 CFU/ml/h with the highest ampicillin-sulbactam dose used (500 and 500 mg/kg of body weight, two doses). This was similar to the bactericidal activity achieved by low-dose ceftriaxone (10 mg/kg), while a higher ceftriaxone dose (100 mg/kg) produced a significant increase in bactericidal activity (1.1 +/- 0.4 log10 CFU/ml/h). It appears that ampicillin-sulbactam, despite favorable CSF pharmacokinetics in animals with meningitis, may be of limited value in the treatment of difficult-to-treat beta-lactamase-producing bacteria, against which the combination shows only moderate in vitro activity.

Topics: Ampicillin; Animals; beta-Lactamases; Ceftriaxone; Drug Therapy, Combination; Escherichia coli Infections; Injections, Intravenous; Meningitis, Bacterial; Microbial Sensitivity Tests; Rabbits; Sulbactam

The incidence of gram-negative bacteremia is significantly increasing in recent years by the wide-spread use of cytotoxic and immunosuppressive drugs. Although, the effective antimicrobial drugs are being used in treatment, the mortality rate is still high. In this study, we searched for the histopathological changes occurring on lung tissue in E. coli sepsis, and their severity in different models. Microscopically, all the specimens were examined by the presence of interstitial and peribronchiolar inflammation, congestive atelectasis, and emphysema. The differences between the ratios of histopathological changes in treatment subgroups were not statistically significant. However, the ratio of interstitial and peribronchiolar inflammation and emphysema was significantly decreased in mice received cyclophosphamide, when compared with control group. Besides, the ratio of peribronchiolar inflammation was significantly increased in mice received steroid when compared with control group.

Topics: Animals; Bacteremia; Ceftriaxone; Cyclophosphamide; Disease Models, Animal; Escherichia coli Infections; Immunosuppression Therapy; Lung; Methylprednisolone; Mice; Steroids

The in vitro activity of four cephalosporins was compared with their effects in an experimental thigh infection (cefuroxime and cefamandole against Escherichia coli and cefamandole, ceftriaxone, and ceftazidime against Klebsiella pneumoniae) in granulocytopenic mice. The effect in vitro (ER) was defined as the difference between the growth rate without antibiotic and the growth rate at the steepest part of a 3-h growth curve in the presence of an antibiotic. The relation between concentration and ER was described with the Hill equation. Using pharmacokinetic parameters of the plasma concentrations in vivo and those of the Hill equation the corresponding time course of ER was calculated and by integration with respect to time (0tERdt), an estimate was obtained of the effect on bacteria. For all four antibiotics this estimate was significantly correlated with the actual values of the effect in vivo (EN), defined as the difference in numbers of bacteria between controls and antibiotic-treated animals at 4 h.

Topics: Agranulocytosis; Animals; Cefamandole; Ceftazidime; Ceftriaxone; Cefuroxime; Cephalosporins; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Klebsiella Infections; Klebsiella pneumoniae; Mice; Protein Binding; Specific Pathogen-Free Organisms

We studied the efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ceftriaxone in vitro and in experimental endocarditis due to an Escherichia coli strain producing an extended-spectrum beta-lactamase most similar to SHV-2, a new mechanism of resistance to broad-spectrum cephalosporins among members of the family Enterobacteriaceae. In vitro, ceftriaxone demonstrated an important inoculum effect (MICs were 2 and 256 micrograms/ml with 5 X 10(5) and 5 X 10(7) CFU of inoculum per ml, respectively). Sulbactam inhibited the beta-lactamase degradation of ceftriaxone and enhanced the killing by ceftriaxone with both inocula tested. In vivo, sulbactam (100 mg/kg every 8 h) or ceftriaxone (15 or 30 mg/kg every 24 h) alone were ineffective after a 4-day therapy. The addition of sulbactam to ceftriaxone (15 mg/kg) or to the ceftriaxone (15 mg/kg)-netilmicin (6 mg/kg every 24 h) combination produced a reduction of 2 log10 CFU/g of vegetation greater than that produced by therapy without sulbactam. The sulbactam-ceftriaxone (30 mg/kg) combination produced a reduction of almost 5 log10 CFU/g of vegetation greater than that produced by single-drug therapy (P less than 0.01), sterilized five of eight vegetations (versus none of seven for ceftriaxone [30 mg/kg] alone; P less than 0.05), and was as effective as the ceftriaxone (15 mg/kg)-sulbactam-netilmicin combination. We concluded that (i) SHV-2 production was responsible for ceftriaxone failure in vivo, probably because of the high inoculum present in vegetations; (ii) sulbactam used in a regimen which provided levels in serum constantly above 4 micrograms/ml and a vegetation/serum peak ratio of approximately 1:3 enhanced the activity of a broad-spectrum cephalosporin in a severe experimental infection; and (iii) the highest dose of ceftriaxone in combination with sulbactam was as effective as the lowest dose of ceftriaxone plus sulbactam plus an aminoglycoside.

Topics: Animals; beta-Lactamase Inhibitors; Ceftriaxone; Drug Combinations; Endocarditis, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Microbial Sensitivity Tests; Netilmicin; Rabbits; Sulbactam

Protein binding, serum kinetics and minimum inhibitory concentrations (MICs) for Staphylococcus aureus were determined for cefoxitin, cefazolin, ceftazidime and ceftriaxone in the rabbit. MICs of cefazolin and cefoxitin were also measured for Escherichia coli. Varying concentrations of the bacteria were administered intradermally to create areas of cellulitis, which were quantified as mean erythematous areas (EAs). Despite large differences in protein binding of the antibiotics (range 12-88%) and antibiotic dosing to allow serum concentrations to drop below the respective MICs, there was no statistical difference in the mean EAs of the animals after bacterial challenge. Antibiotic protein binding did not alter the course of cellulitis nor correlate with bacterial MIC in this model.

Topics: Animals; Bacterial Infections; Biological Availability; Cefazolin; Cefoxitin; Ceftazidime; Ceftriaxone; Cephalosporins; Chromatography, High Pressure Liquid; Escherichia coli Infections; Female; Kinetics; Protein Binding; Rabbits; Staphylococcal Infections

The treatment of Ceftriaxone and IgG in neutropenic (Group A), and in normal (Group B) mice were investigated in experimental E. coli sepsis. IgG was obtained from the rabbits immunized with same strain. The inoculum dose of infection was 4 x 10(8) bacteria/ml in the experiment. The two groups were divided into four subgroups; Control, IgG. Ceftriaxone and Ceftriaxone + IgG groups. The mortality rates of mice in both groups and bacteria growing in organ cultures are investigated and compared. IgG treatment reduced the mortality in the normal mice, but no significant difference was found between two groups. An addition of IgG to Ceftriaxone treatment significantly decreased the mortality rate in both of the groups (p less than 0.05). But a significant difference was not observed between two subgroups treated with IgG and Ceftriaxone.

Topics: Animals; Ceftriaxone; Combined Modality Therapy; Escherichia coli Infections; Immunization, Passive; Immunoglobulin G; Mice; Neutropenia

Experimental E. coli sepsis was constituted in two groups of mice. One of the groups have been immunosuppressed by steroid therapy of ten days (group A) and the other group was normal (group B). Ceftriaxone and Ig G, prepared by vaccinating rabbits with the same strain of E. coli, were used in therapy. The results of the therapy in both were compared. The mortality rate of mice on Ig G therapy was % 70 in group A and % 80 in group B and that on ceftriaxone therapy % 60 and % 50, respectively. The mortality rate was % 30 in both groups with Ig G + ceftriaxone therapy. There wasn't any significance between these. On this research, the treatment of antibiotic together with Ig G decreased the mortality rate. The statistical value of the mortality rate among the treatment groups was not found significant.

Topics: Animals; Ceftriaxone; Combined Modality Therapy; Escherichia coli Infections; Immunoglobulin G; Immunosuppression Therapy; Mice; Rabbits; Steroids

A thigh muscle infection induced with Escherichia coli in irradiated mice was used as a model to compare the in vivo pharmacodynamics of the antibacterial effect of four cephalosporins (i.e., cefepime, ceftriaxone, ceftazidime, and cefoperazone) with the in vitro antibacterial pharmacodynamics of these drugs. The following in vitro pharmacodynamic parameters were determined: the maximum effect as a measure for efficacy, the 50% effective concentration as a parameter for potency, and the slope of the concentration-effect relationship. For analysis of the in vivo antibacterial pharmacodynamics, the same parameters were applied for the dose instead of the concentration. For the detection of a relationship between concentration and antibacterial effect in vivo, we determined the pharmacokinetics of the four cephalosporins in the plasma of mice. The results showed that, in general, there is a direct relationship between the in vivo and in vitro pharmacodynamics of these cephalosporins. The maximum effects of cefepime, ceftazidime, and cefoperazone were approximately similar in vivo and in vitro. The sequence of potency of these drugs was, in descending order, cefepime, ceftazidime, and cefoperazone. Ceftriaxone differed from the other three cephalosporins in that it displayed unexpected in vivo pharmacodynamics. Ceftriaxone was just as efficacious as the other three in vitro, but its maximum effect in vivo was much lower. This relatively low maximum effect of ceftriaxone in vivo was not explained by the pharmacokinetic characteristics of the drug. From the present results it can be concluded that the in vitro efficacy of cephalosporins does not necessarily have a predictive value for the in vivo efficacy.

Topics: Animals; Cefepime; Cefoperazone; Ceftazidime; Ceftriaxone; Cephalosporins; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Escherichia coli; Escherichia coli Infections; Female; Mice

FCE 22101 is a new penem antibiotic with a spectrum of activity suggesting a possible role in the empirical treatment of meningitis. It appears to achieve a mean reduction in bacterial titre in CSF comparable with currently accepted agents for both pneumococcal and Escherichia coli meningitis. Its efficacy may, however, be variable. It does not achieve CSF level/MIC ratios as favourable as imipenem for the pathogens studied. Further studies are necessary to determine its role, if any, in this disease.

Topics: Animals; Anti-Bacterial Agents; Blood Bactericidal Activity; Carbapenems; Ceftriaxone; Escherichia coli Infections; Imipenem; Meningitis; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillins; Rabbits

The effect of sub-MICs of netilmicin and ceftriaxone on the interaction between encapsulated and unencapsulated strains of Escherichia coli and certain host defence mechanisms, i.e. complement activation, opsonization, phagocytosis by human polymorphonuclear leucocytes (PMN), and serum bactericidal activity have been studied. Experiments were carried out testing antibiotics either alone or in combination. Non-capsulated strains of E. coli activated complement rapidly and were easily phagocytosed and killed after opsonization in human pooled serum. Pretreatment of these strains with sub-MICs of antibiotics did not change the rate of opsonization or the degree of uptake by PMN, but did enhance serum sensitivity. Capsulated strains of E. coli were both poorly opsonized and resistant to serum bactericidal activity. Treatment of these strains with sub-MICs of antibiotics enhanced complement consumption as well as phagocytosis by PMN, but did not affect serum-resistance.

Topics: Blood Bactericidal Activity; Ceftriaxone; Complement System Proteins; Escherichia coli; Escherichia coli Infections; Hemolytic Plaque Technique; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Netilmicin; Neutrophils; Opsonin Proteins; Phagocytosis

We evaluated the activities of ceftriaxone (15 mg/kg), netilmicin (6 mg/kg), and their combination given intramuscularly once daily for 4 days for the treatment of experimental Escherichia coli endocarditis in rabbits. In vitro, a greater rate of killing and an increased trough serum bactericidal titer (P less than 0.01) were achieved with the combination. In vivo, the combination had a greater bactericidal effect (P less than 0.01) and resulted in a greater number of sterile vegetations (P less than 0.05) than single-drug therapy. Thus, in vivo, an increased effect can be obtained despite a single daily dose of a long-acting cephalosporin and an aminoglycoside.

Topics: Animals; Ceftriaxone; Drug Combinations; Endocarditis, Bacterial; Escherichia coli Infections; Female; Half-Life; Humans; Male; Netilmicin; Rabbits

In order to assess the in vivo antibacterial activity of two cephalosporins of third generation, cefotaxime and ceftriaxone, we used the model of experimental bacteremia in chickens we had developed for a few years. 93 chickens were inoculated with 10(7) E. coli K1 coming from a meningitis in a new-born baby. 19 chickens were used as a control group; 29 were given ceftriaxone (50 mg/kg); 28 cefotaxime (50 mg/kg) and 17 cefotaxime (100 mg/kg). The antibiotics were injected 4 hours after the inoculation. The bacterial concentrations found in capillaries by using quantitative blood cultures, were significantly lower in the 3 groups of chickens which were given antibiotics than in the control group, at 24, 48 and 72 hours after inoculation. At 24 hours after the inoculation, the bacterial concentration in the chickens treated by ceftriaxone (50 mg/kg) was significantly lower than that found in chickens treated by cefotaxime (50 mg/kg). At 48 or 72 hours the differences of bacterial concentration in the three groups of chickens were not significant. Over 72 hours following inoculation, 4 control and only one treated chickens died. The efficient clearance of E. coli K1 by a single dose of ceftriaxone, found at 24 hours after inoculation, confirms the possibility of using ceftriaxone once daily for serious infections.

Topics: Animals; Cefotaxime; Ceftriaxone; Chickens; Escherichia coli Infections; Injections, Intravenous; Microbial Sensitivity Tests; Models, Biological; Sepsis; Time Factors

We studied the effect of a nonsteroidal anti-inflammatory drug, diclofenac, in rabbits on the kinetics of three cephalosporins: cefotiam, cefmenoxime and ceftriaxone, and compared the antibacterial effect of these antibiotics, given alone or with diclofenac, in experimental endocarditis. Diclofenac significantly increased (P less than .05) the area under the curve in tissue-cage fluid of ceftriaxone and cefotiam-treated animals, and the terminal half-life of ceftriaxone in their sera (3.45 +/- 0.4 vs. 2.8 +/- 0.5 hr). Diclofenac reduced urinary excretion of cefotiam only. Cefmenoxime pharmacokinetics remained unchanged by diclofenac. The alteration of ceftriaxone kinetics appeared to be due to nonrenal mechanisms and could suggest reduction of biliary excretion. In Escherichia coli endocarditis, diclofenac enhanced the concentration (P less than .05) of cefotiam (23 +/- 16 vs. 8.9 +/- 5 micrograms/g) and ceftriaxone (13.2 +/- 3 vs. 8.5 +/- 4 micrograms/g) in infected vegetations, but not that of cefmenoxime. The antibacterial effect of ceftriaxone increased with diclofenac (5.5 +/- 1 vs. 7.2 +/- 1 log10 colony forming unit/g of vegetation). In vitro, neither protein binding to rabbit serum proteins nor intrinsic activity on the E. coli strain of each antibiotic was modified by diclofenac. These results suggest that anti-inflammatory drugs could increase antibiotic efficacy by altering their pharmacokinetics. The renal and nonrenal site of interaction may be involved for drugs belonging to the same class. Results obtained in tissue-cage fluid were predictive of the interference at the infected site.

Topics: Animals; Cefmenoxime; Cefotaxime; Cefotiam; Ceftriaxone; Diclofenac; Drug Synergism; Endocarditis, Bacterial; Escherichia coli Infections; Injections, Intramuscular; Microbial Sensitivity Tests; Rabbits

Ceftriaxone (CTRX) was administered to the newborn and its clinical effectiveness as well as its blood and cerebrospinal fluid levels were studied. 1. Average blood levels of CTRX 1 hour after single intravenous administration were 39 micrograms/ml in 2 cases receiving about 10 mg/kg, 70 micrograms/ml in 2 other cases receiving 20 mg/kg and 208 micrograms/ml in one receiving 52.6 mg/kg. As is apparent from these cases data, blood levels of CTRX were dose dependent. Blood levels of the drug were between 3.7 to 12.4 micrograms/ml 24 hours later. Half-lives of the drug in blood in the 5 newborns ranged from 7.13 to 10.6 hours. In a 53-day-old patient receiving 43.4 mg/kg of CTRX via intravenous injection, the one-hour blood level of the drug was 140 micrograms/ml and the half-life was 3.68 hours. The blood level of the drug 36 hours after single intravenous administration with 17.3 to 20.0 micrograms/ml to 5 other cases 0 to 5 days of age ranged from 4.6 to 13.7 micrograms/ml. 2. The cerebrospinal fluid level of CTRX 4 hours after intravenous administration with 49.6 mg/kg to cases of Escherichia coli meningitis was 9.7 micrograms/ml on the first day following the start of the treatment. It increased to 23.6, 25.2 and 31.0 micrograms/ml on the third, fourth and fifth days, respectively, and then gradually decreased. Cerebrospinal level was still 5.8 micrograms/ml on the 22nd day during the recovery period. These levels were far more than 1,000 times as much as the MIC for the pathogen at the highest level, and more than 100 times even at the lowest level. 3. CTRX was administered via intravenous injection once or twice a day (11.0-39.5 mg/kg in total) to 13 newborns and 3 infants. The efficacy of CTRX was good to excellent in 10 cases for treatment of 11 diseases (sepsis 1, pneumonia 4, urinary tract infection 4 and fetal infection 2) and all the pathogens (Streptococcus agalactiae 1, E. coli 3, Klebsiella pneumoniae 2, Citrobacter diversus 1) disappeared. In 6 cases where CTRX was used prophylactically, infection did not occur at all. The efficacy was excellent in another newborn with E. coli meningitis intravenously receiving 49.6 mg/kg of CTRX twice daily for 25 days. 4. No adverse reactions were observed. Mild eosinophilia was observed in 4 cases. Follow-up examinations of 3 of the 4 cases showed that these abnormal levels were returned to normal.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Bacterial Infections; Ceftriaxone; Escherichia coli Infections; Female; Humans; Infant, Newborn; Injections, Intravenous; Male; Streptococcal Infections; Urinary Tract Infections

To determine the influence of in vitro activity, pharmacokinetic properties, and therapeutic regimen on the antibacterial effect in vivo, we compared three cephalosporins, cefotiam, cefmenoxime, and ceftriaxone, in a rabbit model of experimental Escherichia coli endocarditis after 4 days of treatment. The MBCs of cefotiam, cefmenoxime, and ceftriaxone for the E. coli strain were 0.5, 0.125, and 0.06 microgram/ml, respectively. Killing curves at 10 times the MBC were similar for the three cephalosporins. In serum, the elimination half-life of ceftriaxone was twice as much as the elimination half-life of cefotiam or cefmenoxime (2.8 +/- 0.45 versus 1.4 +/- 0.25 or 1.3 +/- 0.4 h, respectively). Ceftriaxone was much more effective than cefotiam. The bacterial titer in the vegetations (log10 CFU per gram of vegetation) was 7.56 +/- 1 with cefotiam and 2.41 +/- 2.6 with ceftriaxone, as their concentrations were 18 and 466 times higher, respectively, than their MBCs. Although ceftriaxone and cefmenoxime exhibited a similar rate of killing and percentage of protein binding, ceftriaxone was more effective than cefmenoxime at the same regimen of 15 mg/kg twice a day (3.08 +/- 1.1 versus 4.82 +/- 3.2 log10 CFU/g of vegetation). When antibiotic was given as a single daily injection of 30 mg/kg, the antibacterial effect persisted for ceftriaxone, but not for cefmenoxime. The longer elimination half-life and the higher local concentration/MBC ratio of ceftriaxone explained these results. The bacterial titer measured 24 h after the fourth injection of 30 mg of ceftriaxone per kg confirmed that this regimen prevented regrowth of bacteria. These results suggest that the local antibiotic level/MBC ratio roughly correlated with the antibacterial effect and could represent an adequate basis to explain the differences observed between the drugs in vivo. They also demonstrate that, provided that the dose is sufficient, a long-acting broad-spectrum cephalosporin may be effective in severe gram-negative infections, even when given at relatively long dosing intervals, in contrast with a rapidly cleared drug with the same intrinsic activity.

Topics: Animals; Cefmenoxime; Cefotaxime; Cefotiam; Ceftriaxone; Drug Evaluation, Preclinical; Endocarditis, Bacterial; Escherichia coli; Escherichia coli Infections; Kinetics; Rabbits

Unilateral acute pyelonephritis were produced in rabbits by injecting E. coli, using the retrograde route and after a temporary ureteral obstruction. Animals were treated with ceftriaxone IM at a dose of 50 mg/kg/d and 100 mg/kg/d (corresponding to 1 g/d and 2 g/d in humans) either by a single daily injection or by two daily injections at 12th intervals. Sacrifices were performed at day 5 and 7 of therapy. Analysis of bacteriological, morphological and histological data obtained in infected kidneys demonstrates that the single daily injection of ceftriaxone is more effective than the same dose divided in two injections at 12 h intervals. These results are observed as well with low and high doses of ceftriaxone.

Topics: Acute Disease; Animals; Ceftriaxone; Escherichia coli Infections; Evaluation Studies as Topic; Male; Pyelonephritis; Rabbits

In a rabbit model of Escherichia coli endocarditis, we studied the penetration into infected vegetations and the antibacterial effect of ceftriaxone. Ceftriaxone was given at different dosages, alone or with an interfering agent, diclofenac, a nonsteroidal anti-inflammatory drug, to determine the predictive value of the antibiotic levels in serum or infected vegetations on the antibacterial efficacy. Diclofenac increased the serum terminal half-life of ceftriaxone and increased its extravascular diffusion in tissue cage fluid, as well as in infected vegetations, allowing us to obtain various antibiotic concentrations in the infected site. Two hours after the fourth injection, around the time of peak level in serum, we observed a linear relationship between (i) serum and local antibiotic levels in vegetations, (ii) local antibiotic levels in a range of 142 to 600 X MBC and bacterial titer (log10 CFU/g) in vegetations, and (iii) serum antibiotic levels in a range of 800 to 1,400X MBC and bacterial titer in vegetations. In vivo, antibacterial effect was obtained only with high antibiotic levels in vegetations (greater than or equal to 220X MBC). This was confirmed by incubating vegetations sampled from infected animals in rabbit serum containing ceftriaxone (ex vivo experiment). Given once daily at a therapeutic dosage (30 mg/kg) for 4 days, ceftriaxone exhibited good efficacy (log10 CFU/g of vegetation = 2.41 +/- 2.7 versus 7.41 +/- 0.92 in control animals) and prevented regrowth of bacteria until 24 h after the last injection. We concluded that (i) provided the dose is sufficient, a long-acting cephalosporin can prove effective in severe gram-negative infections even when given infrequently, and (ii) serum antibiotic levels around the peak value, reflecting high effective local levels, could predict the therapeutic efficacy and represent a simple test to monitor the clinical course of a severe infectious process.

Topics: Animals; Ceftriaxone; Diclofenac; Diffusion; Endocarditis, Bacterial; Escherichia coli Infections; Myocardium; Protein Binding; Rabbits

Topics: Ceftriaxone; Child; Escherichia coli Infections; Humans; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal

Ciprofloxacin was compared with ceftriaxone in a rabbit model of septic arthritis caused by Escherichia coli. Both agents significantly reduced mean E. coli counts in septic joint fluid (P less than 0.0005 versus untreated controls) and also within infected synovial tissue (P less than 0.01 versus controls). Ciprofloxacin regimens caused a higher frequency (P less than 0.05) of synovial tissue sterilization (53%) than did ceftriaxone (25%).

Topics: Animals; Arthritis, Infectious; Ceftriaxone; Ciprofloxacin; Escherichia coli Infections; Female; Quinolines; Rabbits; Synovial Fluid

The ability of antibiotic combinations to limit the emergence of resistance during therapy was evaluated in a murine model. Peritonitis was produced by injecting a mixture containing 10(8) colony-forming units of bacteria and sterilized talcum into the peritoneum. Two hours later, a single antibiotic dose was administered subcutaneously. The next day, peritoneal bacterial populations were analyzed on Szybalski's gradients. Acquired resistance was recorded when there was at least a fourfold increase in minimum inhibitory concentrations compared with untreated animals. No resistance emerged after amikacin monotherapy (15 mg/kg); however, resistance was frequently observed after monotherapy with ceftriaxone (50 mg/kg) or pefloxacin (25 mg/kg). Resistance to ceftriaxone and pefloxacin emerged, respectively, in 15 percent and 83 percent of animals with Klebsiella pneumoniae, 71 percent and 54 percent with Enterobacter cloacae, 0 percent and 83 percent with Serratia marcescens, 25 percent and 100 percent with Pseudomonas aeruginosa, and 0 percent with both Escherichia coli and Staphylococcus aureus. In mice with K. pneumoniae or E. cloacae infections, any dual combination of amikacin, pefloxacin, and ceftriaxone produced less acquired resistance than did monotherapy. In these animals, the combination of ceftriaxone and pefloxacin abolished all resistance, whereas the combinations of amikacin plus ceftriaxone or amikacin plus pefloxacin reduced the frequency of resistance by more than half. In animals with P. aeruginosa or S. marcescens infections, resistance to pefloxacin diminished or disappeared after treatment with the combinations of pefloxacin plus ceftriaxone or pefloxacin plus amikacin. However, combinations with ceftriaxone resulted in more frequent resistance to ceftriaxone than did ceftriaxone alone. This was the case in P. aeruginosa infections treated with ceftriaxone plus amikacin (p less than 0.01), and in S. marcescens infections treated with ceftriaxone plus pefloxacin (p less than 0.05). Despite these certain notable exceptions, our data confirm that in most cases combination therapy does limit the emergence of resistance.

Topics: Amikacin; Animals; Anti-Bacterial Agents; Ceftriaxone; Drug Resistance, Microbial; Drug Therapy, Combination; Enterobacter; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Female; Klebsiella Infections; Klebsiella pneumoniae; Mice; Mice, Inbred ICR; Norfloxacin; Pefloxacin; Pseudomonas aeruginosa; Pseudomonas Infections; Serratia marcescens; Staphylococcal Infections; Staphylococcus aureus; Time Factors

An acute exudative Escherichia coli pyelonephritis rat model was used to study the influence of progressive pyelonephritis on the efficacy of antibiotic treatment. In this model, transient ureteral obstruction after E. coli bladder inoculation induces early bacterial multiplication in the kidney parenchyma, and the bacterial counts peak by 48 h. The inflammatory response (assessed by the increase in kidney weight) is somewhat delayed, starting 36 h after inoculation and peaking by 72 h. Groups of rats received 4 doses over 48 h of saline, ceftriaxone (100 mg/kg), or ceftriaxone (100 mg/kg) plus gentamicin (4 mg/kg). These treatments were initiated 24, 36, 48, or 72 h after bladder inoculation. Antibiotic treatment started at 24 h was significantly more effective in reducing bacterial counts in the kidney parenchyma than at any later therapy onset. Only when started 24 h after inoculation was the synergistic combination of ceftriaxone plus gentamicin more effective in reducing bacterial counts than ceftriaxone alone. Ceftriaxone and ceftriaxone plus gentamicin regimens started at 24 h reduced significantly (by 42 and 55%, respectively) the incidence of acute exudative pyelonephritis when compared with the incidence in saline-treated controls. Early therapy onset (24 h) strikingly reduced the development of the inflammatory response. This reduction was less marked when antibiotic therapy was started at 36 h and no longer apparent when therapy onset was delayed up to 48 or 72 h. In conclusion, the efficacy of antibiotics in eradicating bacteria from the kidney parenchyma and in preventing acute exudative pyelonephritis was markedly hampered by the development of pyelonephritis.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Escherichia coli Infections; Exudates and Transudates; Gentamicins; Male; Pyelonephritis; Rats; Rats, Inbred Strains; Time Factors

Topics: Cefotaxime; Ceftriaxone; Drug Resistance, Microbial; Escherichia coli Infections; Female; Humans; Meningitis; Middle Aged; Tobramycin

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Kinetics; Mice; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Ticarcillin

Topics: Bacterial Infections; Cefotaxime; Ceftriaxone; Escherichia coli Infections; Gonorrhea; Humans; Pseudomonas Infections

Ceftriaxone was highly active in eliminating Escherichia coli from the cerebrospinal fluid of rabbits infected with experimental meningitis. However, concentrations equal to or greater than 10 times the minimal bactericidal concentration had to be achieved to ensure optimal efficacy (rate of kill, 1.5 log10 CFU/ml per h). In contrast to other beta-lactams studied in this model, ceftriaxone concentrations in cerebrospinal fluid progressively increased, whereas serum steady state was obtained by constant infusion. The percent penetration was 2.1% after 1 h of therapy, in contrast to 8.9% after 7 h (P less than 0.001). In vitro time-kill curves done in cerebrospinal fluid or broth more closely predicted the drug concentrations required for a maximum cidal effect in vivo than that predicted by determinations of minimal inhibitory or bactericidal concentrations.

Topics: Animals; Cefotaxime; Ceftriaxone; Escherichia coli; Escherichia coli Infections; Kinetics; Meningitis; Rabbits; Time Factors

We have tested the effectiveness of several antibiotic regimens, using a rat model of Escherichia coli experimental pyelonephritis that mimics the conditions of severe renal infections in man because the infection is acquired by the ascending route. We found that ceftriaxone, when given for 5 days to rats with severe exudative pyelonephritis, was as effective as the combination ceftriaxone + gentamicin or the reference combination ampicillin + gentamicin. This effectiveness in vivo of the antibiotic alone was achieved despite a marked synergism between the combinations of antibiotics in vitro. This observation suggests that a new and extremely active cephalosporin is as effective in vivo when used alone as when given in combination with an aminoglucoside and provides rationale for testing the use of single antibiotic therapy for clinical situations for which combinations of antibiotics are currently recommended.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Drug Therapy, Combination; Escherichia coli Infections; Gentamicins; Kidney; Male; Pyelonephritis; Rats; Rats, Inbred Strains