cefepime and Escherichia-coli-Infections

To review the efficacy of cefepime for use in infections caused by extended-spectrum beta-lactamase (ESBL)-producing organisms.. A PubMed literature search (May 2000 to June 2017) was performed using the keyword. All human, English language studies evaluating cefepime use for the treatment of ESBL-producing. Studies assessing the use of cefepime for ESBL infections are few, and clinical studies are limited by design and sample size. The largest pharmacokinetic/pharmacodynamic study, a Monte Carlo simulation using data from the U.S. SENTRY antimicrobial surveillance program, evaluating cefepime use for infections due to ESBL-producing organisms found a 95% to 100% probability of target attainment with traditional cefepime dosing regimens. Most clinical studies found that patients treated with cefepime empirically and definitively had higher rates of mortality than those treated with carbapenems. However, in concordance with other studies reporting minimum inhibitory concentration (MIC) data, lower MICs were associated with lower mortality.. Cefepime should be avoided for empiric treatment of suspected ESBL infections and should only be considered for definitive treatment if the MIC ≤1 µg/mL. However, the site and severity of infection, local resistance patterns, and patient-specific risk factors should also help guide antimicrobial selection.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Enterobacteriaceae Infections; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests

Nosocomial infections caused by extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria complicate therapy and limit treatment options. However, the clinical significance of infections caused by ESBL-producing bacteria remains unclear. A critical examination of the literature provides divergent views of the effect of ESBL carriage on morbidity and mortality and suggests that ESBL production may have its most marked effect on ceftazidime. Effective strategies for the empirical and directed treatment of infections caused by ESBL-producing pathogens include the use of carbapenems and, possibly, the fourth-generation cephalosporin cefepime. Studies indicate that the use of cefepime to treat serious nosocomial infections (e.g., bacteremia, pneumonia, and urinary tract infections) is associated with high rates of microbiological and clinical success. The probability of attaining time above the minimum inhibitory concentration targets of at least 70% of the dosing interval, an important pharmacodynamic indicator of clinical success, is higher with cefepime than with other antimicrobials against Escherichia coli and Klebsiella pneumoniae strains exhibiting ESBL phenotypes. However, for non-ESBL-producing strains, there is no difference in the time above the minimum inhibitory concentration between ceftazidime and cefepime. When used appropriately in institutional settings, cefepime reduces the overall use of cephalosporins, thereby decreasing selection pressure for presumptive ESBL-producing pathogens.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactam Resistance; beta-Lactamases; Cefepime; Cephalosporins; Cross Infection; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella; Klebsiella Infections; Treatment Outcome

Due to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC).. This study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10-14 days with PTZ, cefepime, or ertapenem.. A total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC.. Results from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC.. The trial was registered with the Clinical Research Information Service of Korea Centers for Disease Control and Prevention. (KCT0001895).

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Cefepime; Cephalosporins; Cross Infection; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Genotype; Humans; Male; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Republic of Korea; Tazobactam; Urinary Tract Infections

We conducted a randomized, prospective, open comparison to evaluate the efficacy and safety of cefepime and ceftazidime in the treatment of hospitalized patients with suspected gram-negative bacteremia. Twenty-eight patients with signs and symptoms of sepsis were prospectively randomized to receive cefepime (13 patients) or ceftazidime (15 patients). Cultures of blood obtained at entry into the study were positive for 24 (85.7%) of 28 patients. Eight patients had two or more positive pretreatment blood cultures, and the remaining 16 had one positive pretreatment blood culture. The most commonly isolated blood pathogen was Escherichia coli. Eleven of 13 patients treated with cefepime and 12 of 15 patients treated with ceftazidime were clinically cured. Adverse effects attributable to therapy with the study drugs were minimal in both groups of patients and included rash, headache, nausea, and diarrhea. Our results suggest that cefepime is an efficacious and well tolerated as is ceftazidime in the treatment of hospitalized patients with documented gram-negative bacteremia.

Topics: Aged; Bacteremia; Cefepime; Ceftazidime; Cephalosporins; Drug Eruptions; Escherichia coli Infections; Female; Gram-Negative Bacterial Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Prospective Studies; Safety

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

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

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

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

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

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

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

Dengue is an important mosquito-borne tropical viral disease and dual infection, though rare, has been regarded as a risk factor for severe disease and mortality. However, few studies focused on bloodstream infections (BSIs) and empirical antibiotic therapy rarely addressed.. Dengue patients with concurrent or subsequent BSIs between July 1 and December 31, 2015 were included. Clinical information, laboratory data, and drug susceptibility data were collected.. Totally 80 patients, with an in-hospital mortality rate of 32.5%, were included and categorized into three groups. 32 patients in Group I (BSI onset within 48 h after admission), 32 in Group II (between 48 h and one week), and 16 in Group III (more than one week). Patients in Group I were older (mean age: 75.6 vs. 72.6 or 69.6 years; P = 0.01) and had a higher Charlson comorbidity index (3.1 vs. 1.8 or 1.9; P = 0.02) than those in Group II or III. Streptococcus species (28.9%, 11/38) and Escherichia coli (23.7%, 9/38) were major pathogens in Group I. Enterobacteriaceae (38.2%, 13/34) isolates predominated in Group II. Fatal patients more often received inappropriate empirical antibiotic than the survivors (61.5% vs. 35.2%; P = 0.03). According to susceptibility data, pathogens in Group I and II shared similar susceptibility profiles, and levofloxacin, cefepime, or piperacillin/tazobactam, can be empirically prescribed for those hospitalized within one week.. BSI pathogens vary among dengue patients. For adults with dengue and suspected BSI hospitalized within one week, empirical antimicrobial agents are recommended.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Candidemia; Cefepime; Coinfection; Dengue; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli; Escherichia coli Infections; Female; Hospitals; Humans; Levofloxacin; Male; Microbial Sensitivity Tests; Middle Aged; Mortality; Piperacillin, Tazobactam Drug Combination; Retrospective Studies; Risk Factors; Staphylococcal Infections; Streptococcus; Taiwan

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Brazil; Cefepime; Escherichia coli; Escherichia coli Infections; Female; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Carbapenems; Cefepime; Cephalosporins; Ertapenem; Escherichia coli; Escherichia coli Infections; Female; Hospitals, University; Humans; Male; Middle Aged; Pyelonephritis; Republic of Korea; Retrospective Studies; Risk Factors; Treatment Outcome

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Hospitalization; Humans; India; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Penicillanic Acid; Piperacillin; Tazobactam; Treatment Outcome; Young Adult

Validated animal models are required as bridging tools to assess the utility of novel therapies and potential microbiologic outcomes. Herein, we utilized uropathogenic extended-spectrum-β-lactamase (ESBL)-producing and non-ESBL-producing

Topics: Animals; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cefepime; Cephalosporins; Disease Models, Animal; Ertapenem; Escherichia coli Infections; Female; Humans; Levofloxacin; Mice, Inbred ICR; Microbial Sensitivity Tests; Urinary Tract Infections; Uropathogenic Escherichia coli

Urinary tract infections (UTIs) are one of the most common diseases by which humans seek medical help and are caused mainly by uropathogenic Escherichia coli (UPEC). Studying the virulence and antibiotic resistance of UPEC with respect to various phylogenetic groups is of utmost importance in developing new therapeutic agents. Thus, in this study, we analysed the virulence factors, antibiotic resistance and phylogenetic groups among various UPEC isolates from children with UTIs. The phylogenetic analysis revealed that majority of the strains responsible for UTIs belonged to the phylogenetic groups B2 and D. Of the 58 E. coli isolates, 79·31% belonged to group B2, 15·51% to group D, 3·44% to group A and 1·72% to B1. Simultaneously, the number of virulence factors and antibiotic resistance exhibited were also significantly high in groups B2 and D compared to other groups. Among the isolates, 44·8% were multidrug resistant and of that 73% belonged to the phylogenetic group B2, indicating the compatibility of antibiotic resistance and certain strains carrying virulence factor genes. The antibiotic resistance profiling of UPEC strains elucidates that the antimicrobial agents such as chloramphenicol, cefoxitin, cefepime, ceftazidime might still be used in the therapy for treating UTIs.. As the antibiotic resistance pattern of uropathogenic Escherichia coli varies depending on different geographical regions, the antibiotic resistance pattern from this study will help the physicians to effectively administer antibiotic therapy for urinary tract infections. In addition, the frequency of virulence factors and antibiotic resistance genes among various phylogenic groups could be effectively used to draw new targets for uropathogenic Escherichia coli antibiotic-independent therapies. The study emphasizes need of public awareness on multidrug resistance and for more prudent use of antimicrobials.

Topics: Anti-Bacterial Agents; Cefepime; Cefoxitin; Ceftazidime; Cephalosporins; Child; Chloramphenicol; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Escherichia coli Proteins; Humans; Microbial Sensitivity Tests; Phylogeny; Republic of Korea; Urinary Tract Infections; Uropathogenic Escherichia coli; Virulence Factors

Phenotypic heteroresistance (PHR) is common in a weight of microbes and plays an important role in the evolution of antibiotic resistance. However, PHR to cefepime (FEP-PHR) among invasive Escherichia coli (E. coli) has not been reported. This study aimed to report the characteristics of invasive E. coli with FEP-PHR traits and further to investigate the predisposing factors for its acquisition. A retrospective case-control study was conducted in a teaching hospital in Southwest China. A total of 319 successive and non-duplicate E. coli strains were isolated from blood and other sterile body fluids between July 2011 and August 2013. Among the seventy (70/319, 21.9 %) isolates harboring FEP-PHR traits, 30 (42.9 %) isolates were isolated from blood, 14 (20.0 %) isolates were isolated from bile, and 13 (18.6 %) isolates were isolated from drainage. FEP-PHR isolates were verified by population analysis profile (PAP) assays. Male gender, receipt of total parenteral nutrition, cephalosporins exposure, and production of extended spectrum betalactamases (ESBL) were independent risk factors for the acquisition of invasive E. coli with FEP-PHR traits. Pulsedfield gel electrophoresis (PFGE) revealed clonal diversity among the FEP-PHR isolates. The prevalence of heteroresistance to cefepime among invasive E. coli isolates merits great attention and heteroresistance may lead to the emergence of resistance strains. Therefore, systematical analysis of risk factors, careful interpretation of antibiotic susceptibility results and appropriate prescription of therapeutic strategy could help to prevent misreporting and therapeutic failure.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactam Resistance; Bile; Blood; Case-Control Studies; Cefepime; Cephalosporins; China; Drainage; Electrophoresis, Gel, Pulsed-Field; Escherichia coli; Escherichia coli Infections; Female; Genetic Variation; Hospitals, Teaching; Humans; Male; Middle Aged; Molecular Typing; Retrospective Studies; Risk Factors

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

This retrospective study was conducted to evaluate clinical outcomes of bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae and their antibiotic susceptibilities in febrile neutropenic children. Clinical characteristics, prognosis, and antibiotic susceptibilities were reviewed and compared between febrile neutropenic children with bacteremia caused by ESBL-producing and non-ESBL-producing E. coli and K. pneumoniae. A total of 61 episodes of E. coli and K. pneumoniae bacteremia, including 21 episodes (34.4%) due to ESBL-producing strains, were diagnosed. There was no significant factor associated with bacteremia by ESBL-producing strains. Empirical antibiotics were appropriate in 85.7% of the ESBL group and 95.0% of the non-ESBL group. In the entire study population, seven deaths (11.5%), including three deaths (4.9%) due to E. coli and K. pneumoniae bacteremia, occurred. The complication and mortality rates were not significantly different between the two groups. Antibiotic susceptibility rates were significantly lower in the ESBL group than in the non-ESBL group in most antibiotics. Although 52.4% and 66.7% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam and cefepime, respectively, 96.7% of all the isolates and 90.5% of the ESBL-producing isolates were susceptible to piperacillin/tazobactam or cefepime in combination with aminoglycoside. In conclusion, the ESBL group did not show a significantly unfavorable outcome, and empirical therapy with piperacillin/tazobactam or cefepime in combination with aminoglycoside might be more useful for febrile neutropenic children, instead of β-lactam monotherapy in institutions with high prevalence of ESBL-producing E. coli and K. pneumoniae.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Cephalosporins; Child; Escherichia coli; Escherichia coli Infections; Febrile Neutropenia; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Retrospective Studies

Nephrotoxicity due to drugs especially beta lactams and cephalosporins has been well recognised. Cefepime is a fourth-generation cephalosporin that is widely prescribed with few severe adverse reactions reported. Although cefepime induced neurotoxicity has frequently been reported, there is yet no reported case of acute interstitial nephritis caused by this drug. We report a biopsy proven case of acute kidney injury due to acute interstitial nephritis associated with use of cefepime for treatment of mastoiditis and temporal bone osteomyelitis.. A 62-year-old Caucasian female presented with symptoms of right sided mastoiditis. A brain Magnetic Resonance Imaging scan revealed presence of right sided mastoiditis with concurrent temporal bone osteomyelitis. Microbiological specimen isolated an Escherichia coli. Therapy was commenced with intravenous cefepime. After 4 weeks of therapy with intravenous cefepime she developed acute kidney injury. No other medications were taken by the patient. Urine analysis revealed non-nephrotic range proteinuria. There was no red cell casts or white cell casts. Renal biopsy confirmed acute interstitial nephritis as cause of acute kidney injury. Cefepime therapy was ceased and treatment with ciprofloxacin was given to complete the treatment course. Renal function improved only partially with conservative management without any corticosteroid use. To our knowledge this is the first report of cefepime induced interstitial nephritis.. Although cefepime has been considered to be a safe antibiotic from nephrotoxicity point, like other cephalosporins this adverse effect can occur rarely. Physicians need to be mindful of nephrotoxicity associated with its use and careful monitoring of renal parameters should be performed in patients on prolonged therapy with cefepime.

Topics: Acute Kidney Injury; Cefepime; Cephalosporins; Ciprofloxacin; Escherichia coli Infections; Female; Humans; Infusions, Intravenous; Kidney Function Tests; Mastoiditis; Middle Aged; Nephritis, Interstitial; Rare Diseases; Risk Assessment; Treatment Outcome; Withholding Treatment

Extended-spectrum β-lactamase (ESBL)-producing pathogens represent increasing challenges to physicians because of rising prevalence, high mortality, and challenging treatment. Identifying high risks and early appropriate therapy is critical to favorable outcomes.. This is a 5-year retrospective case-case-control study performed at the Detroit Medical Center on adult patients with bloodstream infection (BSI) caused by ESBL-producing and non-ESBL-producing Escherichia coli or Klebsiella pneumoniae, each compared with uninfected controls. Data were collected from December 2004-August 2009. Multivariate analysis was performed using logistic regression.. Participants included 103 patients with BSI caused by ESBL-producing pathogens and 79 patients with BSI caused by pathogens that did not produce ESBLs. The mean age of patients in the ESBL group was 67 years; of the patients, 51% were men, 77% were black, and 38% (n = 39) died in hospital. The mean age of patients in the non-ESBL group was 58 years; of the patients, 51% were men, 92% were black, and 22% (n = 17) died in hospital. On multivariate analysis, predictors of BSI caused by ESBL-producing pathogens included central venous catheter (odds ratio [OR], 29.4; 95% confidence interval [CI], 3.0-288.3), prior β-lactam-/β-lactamase-inhibitor therapy (OR, 28.1; 95% CI, 1.99-396.5), and prior cefepime therapy (OR, 22.7; 95% CI, 2.7-192.4). The only risk factor for BSI caused by non-ESBL-producing pathogens was urinary catheter insertion (OR, 18.2; 95% CI, 3.3-100.3).. Prior antimicrobial therapy, particularly with β-lactam, was the strongest unique risk factor for BSI caused by ESBL-producing E coli or K pneumoniae.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Case-Control Studies; Cefepime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Michigan; Middle Aged; Retrospective Studies; Risk Factors

Antibiotics not only support to alleviate the infections but also facilitate to avert the multiplication of microbes. Due to the irrational use of antibiotics, the resistance of antibiotics has been augmented which results may increase in morbidity and mortality with the span of time. World renowned regulatory bodies like Food and Drug Administration (FDA), Center of Disease Control and Prevention (CDC), and World Health Organization (WHO) vigorously advocate the surveillance of the resistance of antibiotics. During the present study by Kirby-Bauer disk diffusion method 141 clinical isolates of Staphylococcus aureus (n=47, 33.34%), Escherichia coli (n=54, 38.3%), Proteus species (n=26, 18.4%), and Klebsiella pneumoniae (n=14, 9.92%) are evaluated against cefepime and cefpirome which comes of fourth generation cephalosporin. It has been found that cefpirome has better bactericidal activity than cefepime against E. coli and K. pneumoniae while cefepime has been possessed better antibacterial activity against S. aureus and Proteus species which were isolated from respiratory tract infections, blood stream infection, intra-abdominal and urinary tract infections, and skin and soft tissue infections. K. pneumoniae, E. coli, Proteus species, and S. aureus were 34.8%, 26.3%, 11.3%, and 37.7% resistance against cefepime respectively. S. aureus, E. coli, K. pneumoniae, Proteus species has shown 41.4%, 21.7%, 17.6%, and 8.9% resistance against cefpirome correspondingly.

Topics: Anti-Bacterial Agents; Bacteremia; Cefepime; Cefpirome; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; In Vitro Techniques; Intraabdominal Infections; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pakistan; Proteus; Proteus Infections; Respiratory Tract Infections; Skin Diseases, Bacterial; Soft Tissue Infections; Staphylococcal Infections; Staphylococcus aureus; 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

While a lack of concordance is known between gold standard MIC determinations and Vitek 2, the magnitude of the discrepancy and its impact on treatment decisions for extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli are not. Clinical isolates of ESBL-producing E. coli were collected from blood, tissue, and body fluid samples from January 2003 to July 2009. Resistance genotypes were identified by PCR. Primary analyses evaluated the discordance between Vitek 2 and gold standard methods using cefepime susceptibility breakpoint cutoff values of 8, 4, and 2 μg/ml. The discrepancies in MICs between the methods were classified per convention as very major, major, and minor errors. Sensitivity, specificity, and positive and negative predictive values for susceptibility classifications were calculated. A total of 304 isolates were identified; 59% (179) of the isolates carried blaCTX-M, 47% (143) carried blaTEM, and 4% (12) carried blaSHV. At a breakpoint MIC of 8 μg/ml, Vitek 2 produced a categorical agreement of 66.8% and exhibited very major, major, and minor error rates of 23% (20/87 isolates), 5.1% (8/157 isolates), and 24% (73/304), respectively. The sensitivity, specificity, and positive and negative predictive values for a susceptibility breakpoint of 8 μg/ml were 94.9%, 61.2%, 72.3%, and 91.8%, respectively. The sensitivity, specificity, and positive and negative predictive values for a susceptibility breakpoint of 2 μg/ml were 83.8%, 65.3%, 41%, and 93.3%, respectively. Vitek 2 results in unacceptably high error rates for cefepime compared to those of agar dilution for ESBL-producing E. coli. Clinicians should be wary of making treatment decisions on the basis of Vitek 2 susceptibility results for ESBL-producing E. coli.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Genes, Bacterial; Microbial Sensitivity Tests; Polymerase Chain Reaction; Reproducibility of Results

With increase of multi-drug resistant Escherichia coli in community-acquired urinary tract infections (CA-UTI), other treatment option with a therapeutic efficacy and a low antibiotic selective pressure is necessary. In this study, we evaluated in vitro susceptibility of E. coli isolates from CA-UTI to fosfomycin (FM), nitrofurantoin (NI), temocillin (TMO) as well as trimethoprim-sulfamethoxazole (SMX), ciprofloxacin (CIP) and cefepime (FEP). The minimal inhibitory concentrations were determined by E-test or agar dilution method according to the Clinical and Laboratory Standards Institute guidelines, using 346 E. coli collected in 12 Korean hospitals from March 2010 to February 2011. FM, NI and TMO showed an excellent susceptibility profile; FM 100% (346/346), TMO 96.8% (335/346), and NI 99.4% (344/346). Conversely, resistance rates of CIP and SMX were 22% (76/346) and 29.2% (101/349), respectively. FEP still retained an activity of 98.5%. In Korea, NI and TMO in addition to FM are a good therapeutic option for uncomplicated CA-UTI, especially for lower UTI.

Topics: Anti-Bacterial Agents; Cefepime; Cell Survival; Cephalosporins; Ciprofloxacin; Community-Acquired Infections; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Nitrofurantoin; Penicillins; Republic of Korea; Sulfadoxine; Treatment Outcome; Trimethoprim; Urinary Tract Infections

Infections due to fluoroquinolone-resistant Escherichia coli (FQREC) are associated with significant morbidity and mortality. Fluoroquinolone resistance likely arises at the level of gastrointestinal colonization. The objective of this study was to identify risk factors for the development of FQREC gastrointestinal tract colonization in hospitalized patients, including the impact of antibiotics prescribed during hospitalization.. A prospective cohort study was conducted from 2002 to 2004 within a university health system.. Hospitalized patients initially colonized with fluoroquinolone-susceptible E. coli were followed up with serial fecal sampling for new FQREC colonization or until hospital discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQREC colonization, with antibiotic exposure modeled as time-varying covariates.. Of 395 subjects, 73 (18.5%) became newly colonized with FQREC. Length of stay before sampling (hazard ratio [HR], 1.02 [95% confidence interval (CI), 1.1-1.03]; P = .003) and malignancy (HR, 0.37 [95% CI, 0.21-0.67]; P = .001) were significantly associated with the development of FQREC colonization. In addition, receipt of a first-generation cephalosporin (HR, 1.19 [95% CI, 1.10-1.29]; P < .001) or cefepime (HR, 1.05 [95% CI, 1.00-1.10]; P = .048) during hospitalization increased the risk of new FQREC colonization.. The acquisition of FQREC in the hospital setting is complex, and antimicrobial stewardship programs should take into account patterns of antibiotic use in implementing strategies to reduce the development of new FQREC colonization. Future studies are needed to identify risk factors for infection in hospitalized patients newly colonized with FQREC.

Topics: Aged; Anti-Bacterial Agents; Carrier State; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Feces; Female; Fluoroquinolones; Gastrointestinal Tract; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Factors

Increasing resistance of Escherichia coli (E. coli) to antibiotics, especially to the third-generation cephalosporins, has prompted studies on widespread resistance genes such as blaCTX-M and differentiation of E. coli to phylogenetic groups. The aim of this study was to determine the associations between the CTX-M type and the phylogenetic group, the site of infection, and coresistance in Lithuanian E. coli isolates producing β-lactamases. MATERIAL AND METHODS. A total of 90 E. coli ESBL strains were recovered from the lower respiratory tract, the urinary tract, sterile body sites, wounds, and other body sites between 2008 and 2012. The E. coli isolates resistant to at least 2 antibiotics with different modes of action along with resistance to cefotaxime were considered as multiresistant. The blaCTX-M, blaTEM, blaOXA-1, and blaSHV genes, the phylogenetic groups, and the resistance profiles were analyzed. RESULTS. Of the 90 isolates, 84 (93.3%) were classified as multiresistant and 6 (6.6%) as resistant. The blaCTX-M-15 gene was the most prevalent gene followed by the blaCTX-M-14 and blaCTX-M-92 genes. The logistic regression analysis revealed the associations between CTX-M-15 and resistance to ceftriaxone, between CTX-M-14 and resistance to cefoxitin, aztreonam, ampicillin/sulbactam, ticarcillin/clavulanic acid, and tobramycin, and between CTX-M-92 and resistance to cefepime, piperacillin/tazobactam, gentamicin, and tobramycin. CONCLUSIONS. The results of this study showed a significant association between CTX-M-15, CTX-M-14, and CTX-M-92 β-lactamases and resistance to some antibiotics as well as CTX‑M-14 β-lactamase and phylogenetic group A in the Lithuanian population. The associations between the CTX-M type and the site of infection were not determined.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Galanin; Gentamicins; Humans; Lithuania; Phylogeny; Substance P

In this study the efficacy of doripenem, a new broad-spectrum carbapenem, was tested against an Escherichia coli strain and a Klebsiella pneumoniae strain in an experimental animal model. The comparator was cefepime monotherapy.. The rabbit meningitis model was used in this study and the penetration of doripenem through uninflamed and inflamed meninges was determined.. Doripenem, injected three times (75 mg/kg), led to serum peak levels around 100 mg/L and trough levels around 5 mg/L, resulting in a penetration rate of 14% through inflamed meninges and 7% through uninflamed meninges. Against K. pneumoniae, doripenem was slightly but not significantly more efficacious than cefepime over 8 h (5.40 ± 1.37 log(10) cfu/mL versus 3.59 ± 0.89 log(10) cfu/mL for cefepime). Also against the E. coli strain doripenem was slightly superior to the comparator (5.55 ± 0.87 log(10) cfu/mL versus 3.80 ± 1.10 log(10) cfu/mL for cefepime), although the difference was not significant.. Doripenem is a potential monotherapy for the treatment of meningitis due to Gram-negative microorganisms.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Carbapenems; Cefepime; Cephalosporins; Disease Models, Animal; Doripenem; Escherichia coli; Escherichia coli Infections; Klebsiella Infections; Klebsiella pneumoniae; Meningitis, Bacterial; Rabbits; Treatment Outcome

Malakoplakia is a rare granulomatous disorder of unknown etiology and usually affects patients with underlying immunosuppression. This disorder usually involves the genitourinary tract but has been reported in a wide array of anatomical sites. We present a case of extragenitourinary malakoplakia, developing in a patient with a history of plasma cell myeloma, which clinically mimicked recurrent extramedullary myelomatous involvement. Radiologically, this lesion was a 10-cm soft-tissue mass located in the left flank and iliacus muscle. Excisional biopsy revealed a histiocytic infiltrate with histologic features diagnostic of malakoplakia. This case demonstrates the clinical and pathologic diagnostic challenges of malakoplakia arising outside the genitourinary tract. Given that it can closely mimic malignancy in such settings, malakoplakia should be considered in the differential diagnosis of soft-tissue masses developing in patients with hematologic malignancy and iatrogenic immunosuppression. This case highlights the importance for awareness on the part of clinicians, radiologists, and pathologists that malakoplakia can present as a soft-tissue mass.

Topics: Aged; Anti-Bacterial Agents; Cefepime; Cephalosporins; Escherichia coli Infections; Humans; Malacoplakia; Male; Metronidazole; Multiple Myeloma; Neoplasm Metastasis; Soft Tissue Neoplasms; Stem Cell Transplantation

Cefepime is active against bacteria producing chromosomally and plasmid-mediated extended broad-spectrum β-lactamase enzymes. The aim of this study was to evaluate risk factors for acquisition of cefepime resistance in Escherichia coli strains among hospitalized patients in a university hospital in Sanandaj, Iran. The study was a case-control investigation. A case patient was defined as a patient who had one isolate of a cefepime-resistant E. coli strain. A control patient was defined as a patient who had one isolate of a cefepime-sensitive E. coli strain. Cefepime resistance was determined by HiComb MIC tests (HIMEDIA, India). Out of the 255 total isolates, 73 (28.6%) were resistant to cefepime. The previous treatment of cefepime was a risk factor for acquisition of a cefepime-resistant isolate (OR = 6.32, 95% CI: 1.5-25.19, p < 0.007). The use of a ventilator was considered to be a risk for acquisition of a cefepime-resistant isolate (OR = 6.25, 95% CI: 1.86-21.02, p <0.002). The use of a catheter was also found to be a risk factor for acquisition of cefepime resistance (OR = 6.28, 95% CI: 1.86-21.02, p <0.001). There was a significant correlation between days of stay in hospital wards and cefepime resistance (p < 0.003). The main risk factors associated with cefepime resistance were previous treatment with cefepime, use of ventilator, use of catheter and days of stay in ward. More studies are needed to evaluate the role of these factors in order to control the spread of drug resistance.

Topics: Case-Control Studies; Catheters; Cefepime; Cephalosporin Resistance; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Humans; Iran; Length of Stay; Male; Risk Factors; Ventilators, Mechanical

Pyelonephritis is rarely considered in the differential diagnosis of acute kidney injury. Acute non-obstructed bacterial pyelonephritis is an infrequent and rarely considered cause of rapidly progressive acute kidney injury. A diagnostic challenge thus develops as it is difficult to clinically differentiate acute kidney injury secondary to ischemic or toxic acute tubular necrosis or papillary necrosis versus acute interstitial nephritis secondary to drugs or infectious pyelonephritis. We describe a case of acute kidney injury due to suppurative pyelonephritis in an elderly immunocompetent man who presented with dysuria, vomiting, and fever and later found to have histologic and radiologic proven pyelonephritis as the cause of acute kidney injury in the absence of hypotension, nephrotoxic agents, non-steroidal analgesics, immunosuppression, urinary tract obstruction, or other structural anomalies. The patient was managed with antimicrobial therapy, hemodialysis, and a short course of corticosteroids.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Cefepime; Cephalosporins; Diagnosis, Differential; Escherichia coli Infections; Humans; Male; Ofloxacin; Pyelonephritis; Renal Dialysis

Two clinical isolates of Escherichia coli, EC18 and EC21, were non-susceptible (MICs 4-16 mg/L) to cefpirome and cefepime, with marked synergy with clavulanate, yet were susceptible to cefotaxime and ceftazidime (MICs ≤ 1 mg/L). EC19, from the same patient as EC21, was susceptible to all four cephalosporins. We sought to characterize the molecular basis of resistance in isolates EC18 and EC21.. PFGE was used to study the genetic relationships of the isolates, and MICs were determined. β-Lactamases were characterized by PCR, isoelectric focusing (IEF), construction of genomic libraries and sequencing. A double mutant of E. coli J53 was constructed, lacking OmpC and OmpF porins. Plasmids from clinical isolates were transformed into E. coli J53 and J53ΔompCF. Outer membrane proteins (OMPs) were analysed by SDS-PAGE and OmpA by matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass spectrometry. Expression of omp and bla genes was analysed by RT-PCR.. Isolates EC19 and EC21 had identical PFGE profiles, whereas EC18 was distinct. PCR and IEF confirmed β-lactamases with pIs of 5.4 (TEM-1) in EC18 and 7.4 (OXA-1) in both EC19 and EC21. EC18 had bla(TEM-1b) with the strong promoter P5 and lacked OmpC and OmpF. RT-PCR showed stronger expression of bla(OXA-1) in EC21 versus EC19, along with diminished expression of OmpC, though with increased OmpF. Plasmids extracted from EC18 and EC21 conferred increased MICs of cefpirome and cefepime, although susceptibility to cefotaxime and ceftazidime was retained.. The 'cefpiromase' or 'cefepimase' ESBL phenotype of the clinical isolates non-susceptible to cefpirome and cefepime resulted from high expression of TEM-1 or OXA-1 β-lactamases combined with loss of porins.

Topics: Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; beta-Lactamases; Cefepime; Cefpirome; Cephalosporins; Clavulanic Acid; DNA; DNA, Recombinant; Drug Resistance, Bacterial; Electrophoresis, Gel, Pulsed-Field; Enzyme Inhibitors; Escherichia coli; Escherichia coli Infections; Isoelectric Focusing; Microbial Sensitivity Tests; Plasmids; Porins; Reverse Transcriptase Polymerase Chain Reaction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Transformation, Bacterial

Extended-spectrum AmpC beta-lactamase (ESAC) Escherichia coli producers were investigated over a 5-year period. Eleven isolates presenting a strong ampC promoter and different strategic AmpC mutations, including two newly described modifications (A292V and an L-A-A insertion at 295), were characterized. All the isolates belonged to phylogenetic group A and to the ST23 complex.

Topics: Bacterial Proteins; beta-Lactam Resistance; beta-Lactamases; Cefepime; Cefotaxime; Ceftazidime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; France; Hospitalization; Humans; Molecular Sequence Data; Mutation; Phylogeny; Promoter Regions, Genetic

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

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

From 2002 to 2008, there was a significant increase in extended-spectrum beta-lactamase (ESBL)-positive Escherichia coli isolates in European intra-abdominal infections, from 4.3% in 2002 to 11.8% in 2008 (P < 0.001), but not for ESBL-positive Klebsiella pneumoniae isolates (16.4% to 17.9% [P > 0.05]). Hospital-associated isolates were more common than community-associated isolates, at 14.0% versus 6.5%, respectively, for E. coli (P < 0.001) and 20.9% versus 5.3%, respectively, for K. pneumoniae (P < 0.01). Carbapenems were consistently the most active drugs tested.

Topics: Abdomen; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cross Infection; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae

The aim of this research is to evaluate the recent changes in microorganisms causing spontaneous bacterial peritonitis in cirrhotic patients, antibiotic resistance, and response to empirical cephalosporin therapy. A total of 218 patients with ascites secondary to cirrhosis were enrolled. Parenteral cefotaxime or cefepime was given to patients who had a neutrophil count of 250/mm(3) or more or a positive bacterial culture of ascitic fluid. Antibiotic failure was defined by an absence of clinical improvement and an insufficient decrease in neutrophil count of ascites (<25% of initial value) by the third day of therapy. Of all the patients, 44.6% had culture-negative neutrocytic ascites, 24.8% had spontaneous bacterial peritonitis, and 10.1% had monomicrobial nonneutrocytic bacterascites. Growth in culture was observed in 76 patients (34.9%). The two most common isolated bacteria were Escherichia coli (33.8%) and coagulase-negative Staphylococcus (CoNS; 19.7%). The two cephalosporins were effective against E. coli (82%) and but not against CoNS (44%), while levofloxacin showed reasonable activity against both E. coli (71%) and CoNS (90%) in vitro. We confirmed a recent increased incidence of spontaneous bacterial peritonitis caused by Gram-positive bacteria. Levofloxacin seems to be a good alternative treatment for patients with uncomplicated spontaneous ascites infections.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Ascitic Fluid; Bacterial Infections; Cefepime; Cefotaxime; Cephalosporins; Drug Resistance, Bacterial; Enterococcus; Escherichia coli Infections; Female; Humans; Infusions, Intravenous; Klebsiella Infections; Klebsiella pneumoniae; Leukocyte Count; Levofloxacin; Liver Cirrhosis; Male; Microbial Sensitivity Tests; Middle Aged; Neutrophils; Ofloxacin; Peritonitis; Pneumococcal Infections; Pseudomonas aeruginosa; Pseudomonas Infections; Staphylococcal Infections

The optimal approach for empirical antibiotic therapy in patients with severe sepsis and septic shock remains controversial. A retrospective cohort study was conducted in the intensive care units of a university hospital. The data from 760 patients with severe sepsis or septic shock associated with Gram-negative bacteremia was analyzed. Among this cohort, 238 (31.3%) patients received inappropriate initial antimicrobial therapy (IIAT). The hospital mortality rate was statistically greater among patients receiving IIAT compared to those initially treated with an appropriate antibiotic regimen (51.7% versus 36.4%; P < 0.001). Patients treated with an empirical combination antibiotic regimen directed against Gram-negative bacteria (i.e., beta-lactam plus aminoglycoside or fluoroquinolone) were less likely to receive IIAT compared to monotherapy (22.2% versus 36.0%; P < 0.001). The addition of an aminoglycoside to a carbapenem would have increased appropriate initial therapy from 89.7 to 94.2%. Similarly, the addition of an aminoglycoside would have increased the appropriate initial therapy for cefepime (83.4 to 89.9%) and piperacillin-tazobactam (79.6 to 91.4%). Logistic regression analysis identified IIAT (adjusted odds ratio [AOR], 2.30; 95% confidence interval [CI] = 1.89 to 2.80) and increasing Apache II scores (1-point increments) (AOR, 1.11; 95% CI = 1.09 to 1.13) as independent predictors for hospital mortality. In conclusion, combination empirical antimicrobial therapy directed against Gram-negative bacteria was associated with greater initial appropriate therapy compared to monotherapy in patients with severe sepsis and septic shock. Our experience suggests that aminoglycosides offer broader coverage than fluoroquinolones as combination agents for patients with this serious infection.

Topics: Acinetobacter Infections; Adult; Aged; Aminoglycosides; Anti-Bacterial Agents; Carbapenems; Cefepime; Cephalosporins; Cohort Studies; Drug Therapy, Combination; Escherichia coli Infections; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Hospital Mortality; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Pseudomonas aeruginosa; Pseudomonas Infections; Retrospective Studies; Sepsis; Shock, Septic

To evaluate the change of extended spectrum beta-lactamase (ESBLs) Producing Klebsiella Pneumoniae (ESBLs-KPN) and Escherichia coli (ESBLs-ECO) causing nosocomial infection after antimicrobial intervention.. We regularly monitored the data on the yearly consumption [defined as daily dose (DDD) per 1 000 patient-days] of frequently used antibiotics from Dec. 2004 to Dec. 2007. From Jan. 2005 to Dec. 2007, we monitored the resistance of frequently used antibiotics and the timely integrative antimicrobial intervention was based on the outcome of antimicrobial resistance. We also monitored the isolation rate of ESBLs-KPN and ESBLs-ECO causing nosocomial infection. The departments studied were the experimental group and other comparable medical departments were the control group(ICU was excluded).. The isolation rate of ESBLs-KPN (43.90%) and ESBLs-ECO (45.83%) in the experimental group was higher than that in the control group (28.04% and 24.90%, respectively) before the intervention (P<0.05). The isolation rate of ESBLs-KPN decreased (from 26.47% to 17.65%) in the experimental group and that in the control group increased ( ESBLs-KPN: from 34.18% to 52.94%; ESBLs-ECO: from 47.13% to 63.78%) from 2005 to 2007 (P<0.05). The isolation rate of ESBLs-KPN and ESBLs-ECO in the experimental group was lower than that in the control group after the antimicrobial intervention (P<0.05). Usage of ceftazidime and cefoperazone/sulbactam and imipenem was reduced and the consumption of cefepime was increased in the experimental group (P<0.05). Consumption of ceftazidime and cefoperazone/sulbactam and cefepime was increased.. The prevalence of ESBLs-KPN and ESBLs-ECO may be decreased after the integrative antimicrobial intervention.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporins; Cross Infection; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Middle Aged

This study was performed to determine the local etiologic pattern of blood culture isolates and antibiotic resistance in febrile neutropenic patients with hematological malignancies.. A total of 142 blood culture isolates from febrile neutropenic patients admitted to our hematology unit were examined, particularly for the detection of cefepime resistance, because cefepime, a fourth-generation cephalosporin, has been used in our unit as initial therapy for febrile neutropenia.. Among all isolates, 67 (47.2%) were Gram-positive bacteria, the majority of which were fully sensitive to vancomycin. Gram-negative bacteria accounted for 68 (47.9%) of the isolates. Cefepime resistance was seen in 24 (35.3%) of the Gram-negative isolates, and had significantly increased in 2007. The cefepime-resistant isolates primarily consisted of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Approximately 60% of the cefepime-resistant isolates were extended-spectrum β-lactamase (ESBL)-producing organisms. Molecular analysis showed the predominant emergence of CTX-M types. Most of the cefepime-resistant isolates were resistant to third- and various fourth-generation cephalosporins, while having a high susceptibility to carbapenems, particularly meropenem.. Cefepime resistance was often detected in the blood culture isolates from febrile neutropenic patients. This result suggests that therapeutic strategies for febrile neutropenia should be modified based on the local antibiotic resistance patterns.

Topics: Anti-Bacterial Agents; Bacteremia; beta-Lactamases; Cefepime; Cephalosporin Resistance; Cephalosporins; Escherichia coli; Escherichia coli Infections; Fever; Genes, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Klebsiella Infections; Klebsiella pneumoniae; Neutropenia; Pseudomonas aeruginosa; Pseudomonas Infections

A negative extended-spectrum β-lactamase (ESBL) phenotypic confirmation test result obtained after a positive ESBL screening test result but which was cefepime-susceptible (NCPSCS) using the Clinical and Laboratory Standards Institute (CLSI) methods has been observed among isolates of Escherichia coli and Klebsiella spp. in the antimicrobial surveillance program in Shanghai, China. Among isolates collected from Huashan Hospital in 2005, NCPSCS strains were observed in 2.5% of 433 E. coli isolates and in 1.2% of 562 Klebsiella spp. isolates. We then selected 11 E. coli isolates and seven Klebsiella spp. NCPSCS isolates. Transmission electron microscopy (TEM), SHV, plasmid-borne AmpC, and CTX-M type ESBL genes were detected by the polymerase chain reaction (PCR) method. We found that all except two K. pneumoniae strains of NCPSCS isolates producing ESBL and AmpC harbored a plasmid-borne CMY-2 or DHA-1 type AmpC enzyme. The majority of NCPSCS E. coli and K. pneumoniae strains from Shanghai harbor plasmid-borne AmpC enzyme, and we recommend that, when NCPSCS strains are identified, further work such as the PCR detection of ESBL genes is necessary to determine whether they will produce ESBLs. The ESBL-positive strains should be reported as resistant to cefepime according to the CLSI guidelines.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; China; DNA, Bacterial; Escherichia coli; Escherichia coli Infections; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Microscopy, Electron, Transmission; Plasmids; Polymerase Chain Reaction

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

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

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

One hundred twenty-one extended-spectrum beta-lactamse-producing enterobacterial clinical isolates were screened for the qepA gene. A single CTX-M-15-positive Escherichia coli isolate (0.8%) that produced the putative pump QepA2 was identified. This qepA2 gene was located onto a 90-kb mobilizable plasmid that conferred reduced susceptibility to hydrophilic fluoroquinolones.

Topics: Aged; Base Sequence; DNA Primers; DNA, Bacterial; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Female; Fluoroquinolones; France; Genes, Bacterial; Humans; Models, Genetic; Molecular Sequence Data; Plasmids

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

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

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

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

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

This study was designed to compare cefepime exposures with microbiological outcomes in ESBL and non-ESBL infections and determine the pharmacodynamic profiles associated with successful outcome.. Cefepime pharmacodynamic exposures of unbound drug [time above MIC (fT>MIC), minimal concentration over MIC (fC(min)/MIC), and area under the curve over MIC (fAUC/MIC)] for 18 patients with ESBL and non-ESBL infections were determined by using a published population pharmacokinetic model. Classification and regression tree analysis was used to identify pharmacodynamic breakpoints that predicted eradication. A 5000-patient Monte Carlo Simulation was conducted to estimate the probability of target attainment for the goal pharmacodynamic exposures.. Eradication was 80% when fT>MIC was 50% compared with 0% when T>MIC was less than 50% (p<0.05). The median fC(min)/MIC ratio for ESBL group was statistically lower than that for the non-ESBL group (1.54 versus 138, p<0.001). Regardless of ESBL production, all pathogens were eradicated when fC(min)/MIC>7.6 and only 33.3% were eradicated when fC(min)/MIC< or =7.6 (p<0.05). Pharmacodynamic exposures of 50% fT>MIC and fAUC/MIC>1654 were also predictive of eradication. While conventional dosage regimens of 2g q 12h and q 8h failed to achieve adequate target attainment, 4 g continuous infusion and 2g q 6-8h prolonged infusion could attain more than 90% of target attainment at the MIC of 2 microg/ml for the breakpoint of fCmin/MIC=7.6.. Microbiological eradication in patients receiving cefepime was best predicted by fCmin/MIC ratio greater than 7.6 regardless of the presence of an ESBL. Continuous or prolonged infusion regimens provided the greatest probability of attaining this exposure.

Topics: Aged; Anti-Bacterial Agents; beta-Lactamases; Case-Control Studies; Cefepime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella; Klebsiella Infections; Male; Microbial Sensitivity Tests; Middle Aged; Monte Carlo Method; Treatment Outcome

The effect of experimentally induced fever on the pharmacokinetics of cefepime administered intravenously at a dose of 75 mg/kg bw was studied in six healthy rabbits. The study was conducted in two consecutive phases, separated by a washout period of 2 weeks. Infection was induced by the intravenous inoculation of 5 x 10(8) cfu of Escherichia coli 24 h before the pharmacokinetic investigation was carried out. Serial blood samples for cefepime concentration determination were obtained for 48 h following drug administration. The concentrations of cefepime in the plasma were determined by a quantitative microbiological assay using an agar-gel diffusion method employing Bacillus subtilis ATCC 6633 as the test organism, with a level of detectability of approximately 0.10 microg/ml. Cefepime plasma concentrations versus time were evaluated by non-compartmental methods using WinNonLin. Cefepime was well tolerated and no serious adverse events were observed. Rectal temperature increased 1 degree C 24 h post injection in infected animals. Highly significant differences in the blood plasma concentrations of cefepime were observed between febrile and healthy animals at all the sampling times. This could explain the greater area under the plasma level-time curve of the drug in febrile compared with healthy animals. The results from pharmacokinetic calculations showed that both the distribution volume at steady state (V (dss)) and body clearance (CL(tot)) were affected in febrile as compared to healthy animals. The mean values of V (dss) and CL(tot) of cefepime in healthy rabbits were 1.168 L/kg and 0.303 L/kg/h, respectively. As compared with healthy animals, the mean estimates of V (dss) (0.917 L/kg) and CL(tot) (0.205 L/kg per h) of cefepime were significantly lower, whereas t (1/2lambda), MRT and AUMC were significantly higher in febrile rabbits. It is concluded that, although experimental infection had an effect on the disposition kinetics of cefepime in healthy and febrile rabbits, this was not sufficiently pronounced to require alteration of the dosage during disease.

Topics: Acute-Phase Reaction; Animals; Anti-Bacterial Agents; Area Under Curve; Cefepime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Fever; Half-Life; Injections, Intravenous; Male; Rabbits

Topics: Aged; Anti-Bacterial Agents; Aortic Valve; Bacteremia; Cefepime; Cephalosporins; Echocardiography, Transesophageal; Endocarditis, Bacterial; Escherichia coli; Escherichia coli Infections; Follow-Up Studies; Humans; Male; Microbial Sensitivity Tests; Time Factors; Treatment Outcome

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

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

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

A highly cefotaxime- and cefepime-resistant but ceftazidime-sensitive Escherichia coli isolate was recovered from a community-acquired urinary infection of a Greek patient. Susceptibility testing, transfer assays, plasmid analysis as well as PCR and sequencing techniques were used to investigate the underlying mechanism of resistance. The isolate carried a new variant of the bla(CTX-M-3) gene that possessed a T instead of A at nt position 663. Cefotaxime resistance was transferable and carried on a 60 kb plasmid. The bla(CTX-M-3) variant was located downstream of an ISEcp1B element. The emergence of this new derivative indicates further evolution of the worldwide-distributed bla(CTX-M-3) gene.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cefotaxime; Cephalosporin Resistance; Cephalosporins; Child, Preschool; Community-Acquired Infections; Escherichia coli; Escherichia coli Infections; Female; Genetic Variation; Greece; Humans; Microbial Sensitivity Tests; Polymerase Chain Reaction; Urinary Tract Infections

This study examined the effect of experimentally induced fever on the pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six rabbits. The study was carried out in two consecutive phases separated by a two-week washout period. An infection was induced by an intravenous inoculation of 5 x 10(8) colony-forming units of Escherichia coli 24 h before the pharmacokinetic investigation. A quantitative microbiological assay was employed to measure the plasma cefepime concentrations using an agar-gel diffusion method with Bacillus subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection, the rectal temperature in the infected animals increased by 1 degrees C. There was a significant reduction in the elimination halflife by 21.8 % in the febrile rabbits compared to healthy animals. In addition, the infection significantly increased the peak plasma concentrations by 11.9 %, the mean residence time by 19.9 %, the area under the plasmaconcentration-time curve by 53.6 % and the area under the moment curve by 62.3 %. In conclusion, the endotoxin-induced febrile state produced significant changes in the plasma levels as well as some of the pharmacokinetic variables of cefepime in rabbits.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Cefepime; Cephalosporins; Endotoxins; Escherichia coli Infections; Fever; Half-Life; Injections, Intramuscular; Male; Rabbits

(i) To develop a population pharmacokinetics (PK) model for cefepime in patients in intensive care units (ICUs). (ii) To assess the pharmacokinetic-pharmacodynamic profile of various cefepime dosing regimens and to assess their expected probability of target attainment (=PTA expectation value) against common ICU pathogens such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii.. Thirteen ICU patients received cefepime 2 g 12 hourly intravenous (3 min). Twelve blood samples were taken on two occasions: (i) immediately after initial dose; and (ii) between days 3 and 6 after starting therapy. Population PK models were developed using NONMEM. Based on the final covariate model, Monte Carlo simulations were undertaken (n=1000) to simulate free-drug concentrations of cefepime for two administration methods: (i) intermittent bolus administration (IBA); and (ii) continuous infusion (CI). Concentration-time profiles were evaluated by the probability of achieving free-drug concentration above the MIC for >65% of the dosing interval. Finally, using local MIC distributions of E. coli, K. pneumoniae, P. aeruginosa and A. baumannii the PTA expectation values for each dosing administration method were evaluated.. A three-compartment model with zero-order input best described the concentration-time data. The PTA expectation values for E. coli and K. pneumoniae were >90% in all CI doses but only when administered as 1 g every 6 h and higher daily doses for IBA. For the current treatment protocol, 2 g every 12 h, P. aeruginosa and A. baumannii achieved target concentrations of only 54% and 28%, respectively. For P. aeruginosa, a CI of at least 4 g/day was required to achieve a PTA expectation value>90% while for A. baumannii a 6 g/day CI only achieved a PTA expectation value of 75%.. When given as IBA or CI for E. coli and K. pneumoniae, cefepime should be successful in achieving the bactericidal target. For P. aeruginosa higher doses of cefepime (>4 g/day) are required to achieve the required PTA expectation value. Cefepime fails to achieve the bactericidal target even when administered at high doses, e.g. 6 g/day, for A. baumannii.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Adult; Aged; Anti-Bacterial Agents; Cefepime; Cephalosporins; Drug Administration Schedule; Escherichia coli; Escherichia coli Infections; Female; Gram-Negative Bacterial Infections; Humans; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Models, Biological; Pseudomonas aeruginosa; Pseudomonas Infections

An investigation to determine the efficacy of cefepime in treating infections caused by extended spectrum beta-lactamase (ESBL)-producing strains of Klebsiella pneumonia and Escherichia coli was performed. Retrospective chart reviews were conducted on patients who received cefepime and had an ESBL-producing E. coli or K. pneumoniae isolated from a clinical specimen. Among 13 patients with 15 episodes and 17 sites of infection, there were 12 episodic clinical cures, 1 clinical improvement, and 2 failures. Bacteriologic eradication of the infecting organism from the original clinical site was seen in 11 of the episodes with an additional presumed eradication. Cefepime is a potential alternative, in many cases, to the carbapenems for the treatment of infections caused by ESBL-producing bacteria.

Topics: Anti-Bacterial Agents; beta-Lactamases; Cefepime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Humans; Klebsiella Infections; Klebsiella pneumoniae; Retrospective Studies

To determine the affect of ESBL production among Klebsiella species and Escherichia coli on cefepime effectiveness.. This was a retrospective, case-controlled study comparing the clinical and microbiologic responses of patients receiving cefepime for ESBL producing Klebsiella species or E. coli from a non-urine source with matched controls receiving cefepime for non-ESBL strains. Cases with ESBLs were included if they received monotherapy and were clinically evaluable. Non-ESBL controls were matched in a 2:1 ratio based on age, infection site, intensive care unit (ICU) stay, pathogen species and date of hospitalization.. Ten patients receiving cefepime for ESBLs were matched to 20 controls. Most patients received cefepime 1g q12h. Patients receiving cefepime for an ESBL infection were 9.7 (95% CI: 1.4-68.8) and 28.5 (95% CI: 2.6-306.6) times as likely to have an unsuccessful clinical and microbiological response compared with those with a non-ESBL infection. The presence of an ESBL did not have a statistically significant effect on all cause or infection-related mortality.. These data indicate that ESBL production among non-urinary Klebsiella species and E. coli negatively affected cefepime effectiveness. Further studies are required to evaluate if higher doses of cefepime may improve responses in ESBLs that are initially susceptible.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Case-Control Studies; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Klebsiella; Klebsiella Infections; Male; Microbial Sensitivity Tests; Middle Aged; Treatment Outcome

Thirteen clinical isolates of Escherichia coli resistant to ceftazidime that possessed an AmpC and other (beta-lactamases were identified. The effectiveness of different formulations of piperacillin/tazobactam to other beta-lactams was compared. Antibiotic susceptibility testing, polymerase chain reaction, amplification of blaTEM, blaSHV and blaAmpC, and enzyme-linked immunosorbent assays to identify AmpC beta-lactamases were performed. Hydrolysis rates were obtained and residual enzymatic activity was determined. Cefepime and ertapenem were more active than piperacillin/tazobactam. In contrast, increasing the relative proportion of tazobactam improved susceptibility testing. Twenty micromolar tazobactam inhibited total beta-lactamase activity (as measured by nitrocefin hydrolysis rates) by greater than 75% against all isolates tested: in 11 of 13 E. coli isolates, total beta-lactamase activity was inhibited by 90%. The observed differences between MIC determinations and susceptibility to enzymatic inactivation by tazobactam against E. coli containing AmpC and other -lactamases may be due to the final tazobactam concentration achieved in the periplasmic space. Factors determining this are critical considerations in assessing beta-lactamase inhibitor potency.

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Cefepime; Ceftazidime; Cephalosporins; Drug Resistance, Bacterial; Drug Therapy, Combination; Enzyme Inhibitors; Ertapenem; Escherichia coli; Escherichia coli Infections; Lactams; Microbial Sensitivity Tests; Penicillanic Acid; Tazobactam

Cefepime was evaluated in vivo against two inoculum sizes of four strains of Escherichia coli that produced extended-spectrum beta-lactamases (ESBLs) in a murine neutropenic thigh infection model to characterize the pharmacodynamic activity of cefepime in the presence of ESBL-producing bacteria and to evaluate if differences in lengths of cefepime exposure are required with various inocula. Three strains possessed a single enzyme each: TEM-10, TEM-12, and TEM-26. The fourth strain possessed two TEM-derived ESBLs and a third uncharacterized enzyme. Two non-ESBL-producing E. coli strains were included for comparison. Mice received various doses of cefepime to achieve a spectrum of percentages of time the drug was above the MIC (%T>MICs) for each isolate at both inocula. No significant difference in cefepime exposure was required to achieve similar bactericidal effects for ESBL- and non-ESBL-producing isolates when the starting inoculum was 10(5) CFU of E. coli per thigh. The increased MICs observed in vitro for the ESBL-producing strains at 10(7) CFU/ml did not predict the amount of exposure required to achieve a comparable level of bactericidal activity in vivo at the corresponding starting inoculum of 10(7) CFU/thigh. Compared to the cefepime exposure in tests with the lower inoculum (10(5) CFU/thigh), less exposure was required when the starting inoculum was 10(7) CFU/thigh (%T>MIC, 6% versus 26%), such that similar doses (in milligrams per kilogram of body weight) produced similar bactericidal effects with both inocula of ESBL-producing isolates. Equivalent exposures of cefepime produced similar effects against the microorganisms regardless of the presence of ESBL production. Pharmacodynamic profiling undertaken with conventional cefepime MIC determinations predicted in vivo microbial outcomes at both inoculum sizes for the ESBL-producing isolates evaluated in this study. These data support the use of conventional MIC determinations in the pharmacodynamic assessment of cefepime.

Topics: Animals; beta-Lactamases; Cefepime; Cephalosporin Resistance; Cephalosporins; Colony Count, Microbial; Escherichia coli; Escherichia coli Infections; Male; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Muscle, Skeletal; Thigh

Cloning, sequencing, and biochemical analysis identified a novel AmpC-type beta-lactamase conferring resistance to extended-spectrum cephalosporins in an Escherichia coli clinical isolate. This enzyme, exhibiting 14 amino acid substitutions compared to a reference AmpC cephalosporinase of E. coli, hydrolyzed ceftazidime and cefepime significantly.

Topics: Aged; Aged, 80 and over; Amino Acid Sequence; Amino Acid Substitution; Bacterial Proteins; beta-Lactamases; Cefepime; Ceftazidime; Cephalosporin Resistance; Cephalosporins; Cloning, Molecular; DNA, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Kinetics; Molecular Sequence Data

Topics: Aged; beta-Lactamases; Cefepime; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; Integrons; Plasmids

Transrectal prostate biopsy is the most accurate method for prostate cancer diagnosis. Although an antimicrobial prophylaxis is employed in most cases, infectious complications are among the most severe. We present a case of E. coli multirresistant meningitis after transrectal prostate biopsy despite quinolone prophylaxis.

Topics: Aged; Amoxicillin; Biopsy; Brain Damage, Chronic; Cefepime; Cephalosporins; Ciprofloxacin; Clavulanic Acid; Confusion; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Escherichia coli; Escherichia coli Infections; Gentamicins; Humans; Male; Meningitis, Bacterial; Premedication; Prostate; Rectum; Ultrasonography; Vancomycin

The incidence of extended-spectrum beta-lactamase (ESbetaL)-mediated resistance has increased markedly during the past decade. Risk factors for colonization with ESbetaL-producing Escherichia coli and Klebsiella species (ESbetaL-EK) remain unclear, as do methods to control their further emergence.. Case-control study.. Two hospitals within a large academic health system: a 725-bed academic tertiary-care medical center and a 344-bed urban community hospital.. Thirteen patients with ESbetaL-EK fecal colonization were compared with 46 randomly selected noncolonized controls.. Duration of hospitalization was the only independent risk factor for ESbetaL-EK colonization (odds ratio, 1.11; 95% confidence interval, 1.02 to 1.21). Of note, 8 (62%) of the patients had been admitted from another healthcare facility. In addition, there was evidence for dissemination of a single K oxytoca clone. Finally, the prevalence of ESbetaL-EK colonization decreased from 7.9% to 5.7% following restriction of third-generation cephalosporins (P = .51).. ESbetaL-EK colonization was associated only with duration of hospitalization and there was no significant reduction following antimicrobial formulary interventions. The evidence for nosocomial spread and the high percentage of patients with ESbetaL-EK admitted from other sites suggest that greater emphasis must be placed on controlling the spread of such organisms within and between institutions.

Topics: Academic Medical Centers; Adult; Aged; Aged, 80 and over; Ampicillin; Anti-Bacterial Agents; beta-Lactam Resistance; Carrier State; Case-Control Studies; Cefepime; Cephalosporins; Cross Infection; Drug Therapy, Combination; Drug Utilization Review; Escherichia coli Infections; Feces; Female; Formularies, Hospital as Topic; Gentamicins; Hospitals, Community; Hospitals, Urban; Humans; Infection Control; Klebsiella Infections; Length of Stay; Male; Middle Aged; Pennsylvania; Prevalence; Risk Factors; Sulbactam

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Bacteremia; Cefepime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Escherichia coli Infections; Female; Fever; Fever of Unknown Origin; Humans; Infant; Male; Neoplasms; Neutropenia; Staphylococcal Infections; Streptococcal Infections; Treatment Outcome

The efficacies of cefepime and ceftazidime in an experimental Escherichia coli infection in granulocytopenic mice were related to their in vitro activities and their pharmacokinetic profiles. Cefepime had a higher intrinsic activity in vitro than ceftazidime, and it had a different pharmacokinetic profile, resulting in higher peak concentrations in plasma and a longer elimination half-life. To predict the antibacterial efficacy in vivo on the basis of in vitro activity and pharmacokinetics, we applied a mathematical model in which the in vitro effect is expressed as the difference in growth rate between control cultures and cultures grown in the presence of the antibiotic (ER), whereas the in vivo effect is given by the difference in the number of CFU between controls and antibiotic-treated animals (EN). The integral of ER over time, called ERt, was calculated by using in vivo concentrations. A significant linear relationship was found between EN and ERt for different doses at various times up to 4 h after administration, although the slope of this relationship was slightly but significantly less for cefepime (0.44) than for ceftazidime (0.59).

Topics: Animals; Cefepime; Ceftazidime; Cephalosporins; Escherichia coli; Escherichia coli Infections; Male; Mice; Mice, Inbred Strains; Microbial Sensitivity Tests

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